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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id897
      • user_id71
      • trial_status_id7
      • abstract_of_study<p>\n Control of the HIV epidemic remains one of the global health priorities. Despite remarkable progress achieved in decreasing HIV transmission and AIDS-related deaths in the last decade due to development of over 30 antiretroviral drugs, HIV continues to spread, infecting approximately 1.8 million people in 2016. Around a third of people who are HIV positive do not know their status and hence do not receive treatment. For those who know their status: antiretroviral drugs may not be available on a regular reliable basis in many resource-poor settings. In addition to that, they have long-term side effects, their effective use requires rigorous daily compliance and the circulating and/or transmitted viruses have been shown to develop resistance to several antiretroviral drugs. Also, there is unwillingness to take drugs in a surprisingly large proportion of infected individuals, even in the USA. Thus, a safe, effective, prophylactic HIV vaccine remains one of the priorities of HIV/AIDS research, and will be key to any strategy for halting the AIDS epidemic.</p>\n<p>\n Phase 2a clinical trial HIV-CORE (COnserved REgions) 006 is a test of a new combined vaccine regimen to determine safety and immunogenicity in healthy adults in Kenya, Uganda and Zambia. Immune responses may vary between populations and so it is important to confirm that the vaccines are suitable for the people and environment where they will be deployed for protection against HIV/AIDS.This vaccine regimen is designed to work in all parts of the world since there are many different strains of HIV-1, and the virus can change to escape immune responses.</p>\n<p>\n The aim of the trial is to induce effective cytotoxic T lymphocytes (CTL) against HIV-1. These could complement broadly neutralizing antibodies in prophylaxis and play a central role in cure. CTL exert their effector functions by killing HIV-1-infected cells and producing soluble factors, which directly or indirectly counteract the HIV-1 replicative cycle. In future, this approach could be combined, in human efficacy testing, with other immunogens that stimulate humoral responses, with the goal of effectively preventing HIV-1 infections. The central principle of our strategy is to focus T-cell immune responses on the most conserved regions of the HIV-1 proteome. These regions are common to most variants and, if mutated, reduce the ability of the virus to grow; these regions are the “Achilles heel” of HIV-1. Targeting of conserved regions is further enhanced by using ‘mosaic’ proteins, which are designed by computer to maximize the match of the vaccine with global HIV-1 variants and to block common ways the HIV-1 changes to escape the immune response. Vaccines should match circulating HIV-1 variants as much as possible to stop them efficiently. When T cells attack conserved parts of HIV-1 proteins (parts that seldom or never change), the disease is better controlled—this vaccine includes those parts. The HIV-1-derived mosaic genes are called tHIVconsvX and are delivered by two safe, non-replicating vaccine vectors. The ChAdOx1.tHIVconsv1 utilizes engineered vectors derived from chimpanzee adenovirus to deliver a mosaic immunogen tHIVconsv1 .Two vaccine components derived from poxvirus modified vaccinia virus Ankara (MVA), MVA.tHIVconsv3 and MVA.tHIVconsv4 complement each other and will be used as a pair for immunizations.</p>\n<p>\n The human immune system is constitutively exposed to microbial stimulation and any vaccine design and responsiveness needs to be considered in the context of host-microbiota interactions. The first reports on the influence of gut microbiota diversity and composition on responses to vaccination have been emerging for some time. As part of the exploratory endpoints for this trial, we shall characterize the gut microbiome of study participants for composition and richness before and after administration of the study vaccines. These vaccines will be tested for safety in the United Kingdom, in a phase I trial HIV-CORE 005. The tHIVconsvX vaccines have been designed for global use irrespective of the HIV-1 strain and are therefore very suitable for Africa, where multiple strains are responsible for the epidemic, mainly from the HIV-1 families A, D and C. We do not yet know whether the vaccine will have a beneficial effect, no effect, or whether it could cause harm.</p>\n
      • study_title<p>\n A Phase 1 Trial of ChAdOx1- and MVA-vectored Conserved Mosaic HIV-1 Vaccines in Healthy, Adult HIV-1-negative Volunteers in Eastern and Southern Africa</p>\n
      • laymans_summary<p>\n Approximately 36.9 million people are living with HIV, the virus that causes AIDS, and it is estimated that over 1.8 million new infections occurred in 2017. Vaccination is the most effective way to prevent infection, but it has proved extremely difficult to develop an effective vaccine against HIV. At present, there is no licensed vaccine to prevent HIV infection available. One of the main reasons for this is the extraordinary ability of the virus to change itself so that the human immune system does not recognise it.</p>\n<p>\n The purpose of this study is to find out if the study vaccine(s) are safe and how your immune system responds to them. In addition, we hope to learn what kind of side-effects you may experience after receiving the study vaccine(s), and how severe those side effects will be.</p>\n<p>\n New types of vaccines have been developed at the University of Oxford, United Kingdom. These follow on from similar vaccines which have been given to several hundred healthy volunteers, and to a smaller number of HIV infected patients. In all these studies the vaccines were shown to be safe and well tolerated. However, this is the first time that these particular vaccines will be given sequentially to people.</p>\n<p>\n Three vaccines, called tHIVconsv1, tHIVconsv3; and tHIVconsv4 contain man-made parts of HIV. Only parts of the virus that cannot change are included in the vaccine. The aim is to direct the body to respond to these parts of HIV which the virus cannot easily change to escape from the immune system’s detection. In order to be effective, the three vaccines are carried into the human body by carriers. These are harmless viruses.</p>\n<p>\n Research in Oxford has shown that strong immune responses against HIV-1 are achieved when these types of vaccines, using two or three different carriers, are administered. The vaccine carriers being used in this study are named ChAdOx1 and MVA. ChAdOx1 is a man-made virus that is not capable of multiplying in human beings. It is obtained from a virus that causes infections in chimpanzees and it is harmless in humans. This carrier will deliver the tHIVconsv1 vaccine.</p>\n<p>\n The ChAdOx1.tHIVconsv1 vaccine has not been tested in humans before. MVA is a man-made virus that is not capable of multiplying. It is derived from a weakened form of the smallpox vaccine and is not capable of causing disease. This carrier will deliver tHIVconsv3 and tHIVconsv4 vaccines. The two vaccines, MVA.tHIVconsv3 and MVA.tHIVconsv4 will be used as a pair for immunizations. MVA.tHIVconsv3 and MVA.tHIVconsv4 vaccines have been tested in only a small number of humans The three vaccines tested in this study are man-made and do not contain live HIV-1, therefore they cannot give people HIV-1 infection or AIDS. Earlier forms of similar vaccines were tested and found to be safe and to stimulate the immune system. The aim of this study is to confirm that the three vaccines are safe and can stimulate the immune system of people in Kenya, Uganda and Zambia</p>\n
      • short_titleHIV-CORE 006
      • protocol_noECCT/20/06/09
      • version_noversion 2.0
      • date_of_protocol02-01-2020
      • study_drugC1; ChAdOx1.tHIVconsv1 M3; MVA.tHIVconsv3 M4; MVA.tHIVconsv4
      • disease_conditionHIV
      • product_type_biologicals1
      • product_type_proteins0
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      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjnyange@kaviuon.org
      • applicant_covering_letter1
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      • declaration_applicantProfessor Walter Jaoko, MBChB, MTropMed, PhD,
      • declaration_date130-06-2020
      • declaration_principal_investigatorProfessor Walter Jaoko, MBChB, MTropMed, PhD,
      • declaration_date230-06-2020
      • placebo_presentYes
      • study_objectives<p>\n PRIMARY Safety</p>\n<p>\n ï‚· To evaluate the safety and tolerability of a prime boost vaccine regimen utilizing non-replicating simian adenovirus (ChAdOx1) followed by non-replicating poxvirus modified vaccinia virus Ankara (MVA) in adults in Eastern and Southern Africa Immunogenicity ï‚· To evaluate the specific T-cell immune responses induced by the ChAdOx1.tHIVconsv1 followed by MVA.tHIVconsv3&4 vaccines in vaccine recipients.</p>\n<p>\n SECONDARY</p>\n<p>\n ï‚· To assess tHIVconsvX-specific T-cell responses of for their frequency, breadth and duration in vaccine recipients. ï‚· To assess functional T-cell responses in vaccine recipients that inhibit replication in vitro of viruses of major HIV-1 clades A, B, C and D.</p>\n<p>\n EXPLORATORY</p>\n<p>\n ï‚· To assess induction of plurifunctional tHIVconsvX-specific memory T cells in the vaccine recipients. ï‚· Characterization of the gut microbiome composition and richness. ï‚· Feasibility of recruiting required sample size across all sites within 16 weeks ï‚· Feasibility of retaining at least 90% of enrolled volunteers to end of study.</p>\n
      • principal_inclusion_criteria<p>\n INCLUSION CRITERIA 1.Healthy male and female as assessed by a medical history, physical exam, and laboratory tests. 2.At low risk of HIV infection and willing to maintain low-risk behaviour for the duration of the trial. Individuals from key populations are not excluded provided they are assessed to be at low risk of HIV infection at screening and are willing to maintain low-risk behaviour during the study. 3.At least 18 years of age on the day of screening and have not reached their 51st birthday on the day of the first vaccination. 4.Willing and able to give informed consent for participation in the trial before any study-related procedures are performed. Volunteers will pass an Assessment of Understanding before signing the consent form. 5.Willing to comply with the requirements of the protocol and be available for follow up for the planned duration of the study. 6.Willing to undergo HIV testing, risk reduction counselling, receive HIV test results 7.All sexually active males (unless anatomically sterile or in a monogamous relationship with a female partner who uses a documented non-barrier method of birth control) must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until 4 months after the last vaccination. 8.If a female of childbearing potential, willing to use an effective non-barrier method of contraception (hormonal contraceptive or intrauterine device) from at least 2 weeks prior to first vaccination until at least 4 months after the last study vaccination. If not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level >40 IU/L) or surgically sterile: no additional contraception required. 9.All female volunteers must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures and must test negative prior to each study vaccination. 10.Willing to forego donations of blood or any other tissues during the trial and, for those who test positive for HIV antibodies due to vaccination (vaccine-induced seropositivity/ reactivity), until the anti-HIV antibody titres become undetectable.</p>\n
      • principal_exclusion_criteria<p>\n EXCLUSION CRITERIA 1.Confirmed HIV-1 or HIV-2 infection 2.Receipt of any vaccine in the previous 28 days or planned receipt within 28 days of Investigational Medicinal Product. 3.Participation in another clinical trial of an Investigational Medicinal Product currently, within the previous 3 months or expected participation during the study. 4.Receipt of another investigational HIV vaccine candidate or investigational adenoviral vectored vaccine (Note: receipt of an HIV vaccine placebo will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval). 5.Receipt of blood transfusion or blood-derived products within the previous 4 months or expectation of receiving blood products during the study period. 6.Receipt of immunoglobulin products within the previous 3 months. 7.If female, pregnant or planning a pregnancy during the period of enrolment until 4 months after the last study vaccination; or lactating. 8.Any clinically relevant abnormality on history or examination such as: a. Any confirmed or suspected history of immunodeficiency including recurrent severe infections; b. Use of systemic corticosteroids for >14 days (use of topical or inhaled steroids is permitted) within the previous 6 months; c. Immunosuppressive, anti-cancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months. d. History of splenectomy. e. History of autoimmune disease f. Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions). (Note: a volunteer that states that he or she has easy bruising or bleeding but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience is eligible) g. History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, or clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow up). h. History of cancer (except basal cell carcinoma of the skin) i. Asthma that is not well controlled. j. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine k. History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulty, angioedema). l. History of Guillain-Barre syndrome. m. Confirmed diagnosis of active or chronic hepatitis B, hepatitis C, active syphilis and/or active tuberculosis n. Seizure disorder: an individual who has had a seizure in the last 3 years is excluded (Not excluded: an individual with a history of seizures who has neither required medication nor had a seizure for three or more years). o. History of serious psychiatric conditions or any psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years. p. Substance abuse disorder that precludes compliance with the protocol as assessed by the investigator. q. Any clinically significant acute or chronic medical condition that is considered unstable/progressive, or in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer’s ability to participate in the study 9.Abnormal clinically significant abnormal finding on screening biochemistry or haematology blood, or urinalysis, including but not limited to: Haematology: a. Haemoglobin - <9.5 g/dl in females; <11.0 g/dl in males b. Absolute Neutrophil Count (ANC) – ≤1,000/mm3 c. Absolute Lymphocyte Count (ALC) – ≤650/mm3 d. Platelets - <100,000 cells/mm3 Chemistry e. Creatinine >1.1 x upper limit of normal (ULN) f. AST >1.25 x ULN g. ALT >1.25 x ULN Urinalysis h. Clinically significant abnormal dipstick confirmed by microscopy: i. Protein = 2+ or more j. Blood = 2+ or more (not due to menses) 10. Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the study 11. If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.</p>\n
      • primary_end_points<p>\n PRIMARY Safety</p>\n<p>\n ï‚· Proportion of volunteers with local and systemic reactogenicity events from Day 0 to Day 7 post vaccination ï‚· Proportion of volunteers with Grade 3 or 4 unsolicited adverse events through 28 days post final vaccination ï‚· Proportion of volunteers with vaccine related serious adverse events (SAEs) collected throughout the study period Immunogenicity ï‚· Proportion of vaccine recipients developing HIV-1-specific T-cell responses</p>\n<p>\n SECONDARY</p>\n<p>\n ï‚· Frequency, breadth and duration of T-cell responses to conserved epitopes measured in IFN-γ ELISPOT assay in each vaccine recipientBreadth of inhibition of HIV-1 viruses representative of circulating viruses in Kenya, Uganda and Zambia and other global clades in the in vitro Virus Inhibition Assay</p>\n<p>\n EXPLORATORY</p>\n<p>\n ï‚· Proportions of mono-, bi- and tri-functional T cells in the vaccine recipients ï‚· Shotgun sequencing and metabolomic analyses. ï‚· Proportion of target number of volunteers enrolled within 16 weeks ï‚· Proportion of enrolled volunteers that are retained in the study through the final study visit.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
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      • scope_pharmacodynamic0
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      • scope_dose_response0
      • scope_pharmacogenetic0
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      • scope_pharmacoecomomic0
      • scope_others0
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      • trial_human_pharmacology1
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
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      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Number of Staff: 1 physician, I pharmacist, 2 pharmacy staff, 2 trial clinicians, 3 nurse counselors, 2 community staff, 1 data IT/Data manager, 3 Data staff and 8 lab staff, I labaratory Manager</p>\n<p>\n Core Staff: 1. Dr. Gaudensia N. Mutua MBChB MPH Sub- Investigator 2. Dr Moses Masika MBChB MSc TID,Laboratory Manager 3 Rose Sajabi KRCHN, BA, MA Counselling PSY Study Coordinator,4. Jacquelyn Nyange RN, BA, MSc. Clinical PSY Regulatory compliance</p>\n<p>\n Site Facities: Clinic, Labaratory, data and Pharmacy space available on site Emergency Facities: Well equiped Emergecy room in the clinic</p>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration52 weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
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      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
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      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites2
      • multi_country_listKenya, Zambia,Uganda.
      • data_monitoring_committeeYes
      • total_enrolment_per_site22
      • total_participants_worldwide88
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameN/A
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      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailwjaoko@kaviuon.org
      • organisations_transferred_No
      • number_participants22
      • notification
      • approval_date09-09-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted30-06-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
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      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication approved by the expert committee
      • final_report(null)
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      • balance_site(null)
      • final_date(null)
      • modified2024-01-19 10:51:11
      • created2020-05-27 18:39:00
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
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        • id561
        • application_id897
        • given_nameProfessor Walter Jaoko,
        • middle_name
        • family_name Jaoko,
        • qualificationMBChB, MTropMed, PhD
        • professional_addressDepartment of Medical Microbiology University of Nairobi Second Floor, paola.cicconi@ndm.ox.ac.uk
        • telephone+254-2-2717694 / +254 727555254
        • emailWjaoko@kaviuon.org
        • created2020-06-15 09:15:40
        • modified2020-06-30 11:11:52
    • SiteDetail(array)
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        • id783
        • application_id897
        • county_id47
        • site_nameKAVI-Institute of Clinical Research
        • physical_addressKangemi Health centre
        • contact_detailsPO Box 19676-00202, +254 727555254
        • contact_personProf Walter Jaoko
        • site_capacity(null)
        • misc(null)
        • created2020-06-15 09:15:40
        • modified2020-06-30 11:11:52
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id790
        • application_id897
        • county_id3
        • site_nameKEMRI/ Wellcome Trust Research Programme
        • physical_addressHospital Road
        • contact_detailsP.O. Box 230-80108 Kilifi
        • contact_personProf. Eduard Sanders, MD, MPH, PhD
        • site_capacity(null)
        • misc(null)
        • created2020-06-30 10:30:49
        • modified2020-06-30 11:11:52
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
    • Sponsor(array)
      • 0(array)
        • id436
        • application_id897
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personDr Paola Cicconi, MD, PhD
        • addressThe Jenner Institute University of Oxford Centre for Clinical Vaccinology and Tropical Medicine (CCVTM) Churchill Hospital, Old Road Oxford OX3 7LE United Kingdom
        • telephone_number+44 (0)1865 611413
        • fax_number
        • cell_number+44 (0)1865 611413
        • email_addresspaola.cicconi@ndm.ox.ac.uk
        • created2020-06-15 09:15:40
        • modified2020-06-30 11:11:52
  • 1(array)
    • Application(array)
      • id937
      • user_id81
      • trial_status_id7
      • abstract_of_study<div>\n Over 1.8 million people are infected with HIV globally every year. With long term treatment side effects and emerging drug resistance to available therapy, a safe and effective prophylactic HIV vaccine is key to halting the epidemic. We propose to evaluate the safety and immunogenicity among healthy adults in Kenya, Uganda and Zambia of three vaccines, called tHIVconsv1, tHIVconsv3; and tHIVconsv4. The vaccine regimen consists of a single mosaic prime ChAdOx1.tHIVconsv1 (C1, injected in both arms) and a dual boost of modified vaccinia virus Ankara (MVA) MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) each injected separately into separate arms at the same visit. This combination of HIV vaccines will be a first-in human trial. </div>\n<div>\n  </div>\n<div>\n The vaccines will be tested in parallel for safety in the United Kingdom, in a phase I trial. The safety and immunogenicity of a range of MVA and ChAdOx1-vectored vaccines has been demonstrated in numerous preclinical studies in mice and non-human primates, and in a number of clinical studies, in both healthy and HIV-1-infected volunteers. In this multicenter study, we will conduct a double-blind trial and randomize 88 HIV-uninfected healthy volunteers aged 18-50 years who are at low risk of HIV, to receive either a vaccine or a placebo at 2 vaccination visits 4 weeks apart. Enrolment will be over 16 weeks with each volunteer participating in the trial for approximately 52 weeks.</div>\n<div>\n  </div>\n
      • study_title<p>\n A Phase 1 Trial of ChAdOx1- and MVA-vectored Conserved Mosaic HIV-1 Vaccines in Healthy, Adult HIV-1-negative Volunteers in Eastern and Southern Africa. </p>\n
      • laymans_summary<div>\n <strong>Lay Title:</strong> A study to test three experimental HIV vaccines in healthy adults</div>\n<div>\n  </div>\n<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Approximately 36.9 million people are living with human immunodeficiency virus (HIV), the virus that causes AIDS, and it is estimated that over 1.8 million new infections occurred in 2017. Vaccination is the most effective way to prevent infection, but it has proved extremely difficult to develop an effective vaccine against HIV. At present, there is no licensed vaccine to prevent HIV infection available. One of the main reasons for this is the extraordinary ability of the virus to change itself so that the human immune system does not recognise it and the virus escapes detection. </div>\n<div>\n  </div>\n<div>\n To address differences in HIV, new types of vaccines have been developed at the University of Oxford, United Kingdom. Three vaccines, called tHIVconsv1, tHIVconsv3; and tHIVconsv4 contain artificial pieces similar to parts of HIV and will be tested in this study. The three vaccines are man-made and do not contain live HIV-1, therefore they cannot give people HIV-1 infection or AIDS. These vaccines are being tested for the first time in human beings.</div>\n<div>\n  </div>\n<div>\n <strong>What questions are we trying to answer?</strong></div>\n<div>\n The study aims to find out if the study vaccines are safe and how the body immune system responds to them.  In addition, the study aims to learn what kind of side effects will be experienced after receiving the study vaccines, and how severe those side effects will be. </div>\n<div>\n  </div>\n<div>\n Where is the study taking place, how many people does it involve and how are they selected?</div>\n<div>\n The study will be carried out at 4 research centers in Kenya, Uganda and Zambia involving a total of 88 healthy HIV-1-uninfected male and female adults aged 18-50 years. In Kenya, approximately 44 participants will be enrolled at KAVI-ICR in Nairobi, and the KEMRI-clinic in Mtwapa. In Mtwapa, approximately 22 participants will be enrolled from an HIV-1 vaccine feasibility cohort study.  In Mtwapa, participants who are > 30 years of age, and have been in follow up for more than two years, who in the opinion of the principal investigator or designee, understand the study and provide written informed consent, and are willing to use an effective method of contraception, will be invited for study screening.</div>\n<div>\n  </div>\n<div>\n A person will not participate in this study if he/she has a confirmed HIV infection; is pregnant or breastfeeding; has a serious or long-lasting disease; has abnormal laboratory test results; has recently received vaccination or blood products; has previously received an HIV vaccine; or has a history of severe local or systemic reactions to vaccination. </div>\n<div>\n  </div>\n<div>\n <strong>What does the study involve for those who are in it?</strong></div>\n<div>\n Blood, urine tests and body examinations will be done to check the general health and ensure they meet the requirements to participate in the research. If eligible and agree to participate, they will be assigned (like a flip of the coin) to receive 4 injections of the trial vaccine or 4 injections of a placebo – 2 injections at an initial visit (in one arm each) and another 2 injections (in one arm each), four weeks later. They will be asked to come to the clinic for follow up visits. A diary to record and report any signs or symptoms experienced after vaccination will be given.  A training on how to use the diary will be done. </div>\n<div>\n  </div>\n<div>\n <strong>What are the benefits and risks/costs of the study for those involved?  </strong></div>\n<div>\n There are no direct benefits of participating in the study. Volunteers will get information on their health and HIV status. With any vaccination, there is a possibility of temporary soreness around the injection site; redness, pain, swelling, itching, bruising, a warm feeling and flu-like symptoms.  There may be rare serious adverse events that occur as well with many available vaccines; these include allergic reactions and, rarely, conditions that could affect the nervous system. Volunteers will have close oversight and treatment from the study clinical team. </div>\n<div>\n  </div>\n<div>\n Following administration of an HIV vaccine, some HIV-1 tests may give a false positive result. If this occurs, we will use other tests to help distinguish true HIV from a false result due to vaccination. We will provide diagnostic HIV testing certification to show this. Volunteers who test positive due to study vaccination will also be followed up until the HIV test becomes negative including after study completion.  The vaccine to be used has not been proven to protect against HIV infection. Volunteers may acquire HIV during the study and will be linked to appropriate HIV care and treatment. </div>\n<div>\n  </div>\n<div>\n The safety of the vaccine to an unborn baby is not known. Female volunteers joining the study will be advised to use effective family planning methods. For those who become pregnant during the study, we will continue to follow them up until the baby is born and assess for safety of the baby. </div>\n<div>\n  </div>\n<div>\n <strong>How will the study benefit society?  </strong></div>\n<div>\n The information we collect from this study may help develop a safe and effective HIV vaccine which would ultimately benefit the local and global community.</div>\n<div>\n  </div>\n<div>\n <strong>When does the study start and finish?</strong></div>\n<div>\n The study will start shortly after ethical and regulatory approvals have been obtained. The study duration for participants once enrolled is one year. It is envisaged that the study will be completed by Dec 2021. </div>\n<div>\n  </div>\n<div>\n  </div>\n
      • short_titleHIV-CORE 006
      • protocol_noECCT/20/10/01
      • version_no2.1
      • date_of_protocol06-05-2020
      • study_drugChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVconsv4
      • disease_conditionHIV
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr Clara Agutu
      • declaration_date114-10-2020
      • declaration_principal_investigatorProf Eduard Sanders (Principal Investigator)
      • declaration_date214-10-2020
      • placebo_presentYes
      • study_objectives<div>\n PRIMARY</div>\n<div>\n Safety</div>\n<ul>\n <li>\n To evaluate the safety and tolerability of a prime boost vaccine regimen utilizing non-replicating simian adenovirus (ChAdOx1) followed by non-replicating poxvirus modified vaccinia virus Ankara (MVA) in adults in Eastern and Southern Africa</li>\n <li>\n Immunogenicity</li>\n <li>\n To evaluate the specific T-cell immune responses induced by the ChAdOx1.tHIVconsv1 followed by MVA.tHIVconsv3&4 vaccines in vaccine recipients.</li>\n</ul>\n<div>\n SECONDARY</div>\n<ul>\n <li>\n To assess tHIVconsvX-specific T-cell responses of for their frequency, breadth and duration in vaccine recipients.</li>\n <li>\n To assess functional T-cell responses in vaccine recipients that inhibit replication in vitro of viruses of major HIV-1 clades A, B, C and D.</li>\n</ul>\n<div>\n EXPLORATORY</div>\n<ul>\n <li>\n To assess induction of plurifunctional tHIVconsvX-specific memory T cells in the vaccine recipients.</li>\n <li>\n Characterization of the gut microbiome composition and richness.</li>\n <li>\n Feasibility of recruiting required sample size across all sites within 16 weeks</li>\n <li>\n Feasibility of retaining at least 90% of enrolled volunteers to end of study.</li>\n</ul>\n
      • principal_inclusion_criteria<div>\n Study Population</div>\n<div>\n The study population consists of healthy HIV-uninfected male or female adults aged 18-50 years, who are at low risk of HIV infection, based on a HIV risk assessment at screening, in Kenya, Uganda and Zambia.</div>\n<div>\n  </div>\n<div>\n Inclusion Criteria</div>\n<ul>\n <li>\n Healthy male and female as assessed by a medical history, physical exam, and laboratory tests.</li>\n <li>\n At low risk of HIV infection and willing to maintain low-risk behaviour for the duration of the trial. Individuals from key populations are not excluded provided they are assessed to be at low risk of HIV infection at screening and are willing to maintain low-risk behaviour during the study.</li>\n <li>\n At least 18 years of age on the day of screening and have not reached their 51st birthday on the day of the first vaccination.</li>\n <li>\n Willing and able to give informed consent for participation in the trial before any study-related procedures are performed. Volunteers will pass an Assessment of Understanding before signing the consent form.</li>\n <li>\n Willing to comply with the requirements of the protocol and be available for follow up for the planned duration of the study.</li>\n <li>\n Willing to undergo HIV testing, risk reduction counselling, receive HIV test results</li>\n <li>\n All sexually active males (unless anatomically sterile or in a monogamous relationship with a female partner who uses a documented non-barrier method of birth control) must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until 4 months after the last vaccination.</li>\n <li>\n If a female of childbearing potential, willing to use an effective non-barrier method of contraception (hormonal contraceptive or intrauterine device) from at least 2 weeks prior to first vaccination until at least 4 months after the last study vaccination. If not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level >40 IU/L) or surgically sterile: no additional contraception required.</li>\n <li>\n All female volunteers must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures and must test negative prior to each study vaccination.</li>\n <li>\n Willing to forego donations of blood or any other tissues during the trial and, for those who test positive for HIV antibodies due to vaccination (vaccine-induced seropositivity/ reactivity), until the anti-HIV antibody titres become undetectable.</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Confirmed HIV-1 or HIV-2 infection</li>\n <li>\n Receipt of any vaccine in the previous 28 days or planned receipt within 28 days of Investigational Medicinal Product.</li>\n <li>\n Participation in another clinical trial of an Investigational Medicinal Product currently, within the previous 3 months or expected participation during the study.</li>\n <li>\n Receipt of another investigational HIV vaccine candidate or investigational adenoviral vectored vaccine (Note: receipt of an HIV vaccine placebo will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval).</li>\n</ul>\n<div>\n <ul>\n <li>\n Receipt of blood transfusion or blood-derived products within the previous 4 months or expectation of receiving blood products during the study period.</li>\n <li>\n Receipt of immunoglobulin products within the previous 3 months.</li>\n <li>\n If female, pregnant or planning a pregnancy during the period of enrolment until 4 months after the last study vaccination; or lactating.</li>\n <li>\n Any clinically relevant abnormality on history or examination such as:\n <ul>\n <li>\n Any confirmed or suspected history of immunodeficiency including recurrent severe infections;</li>\n <li>\n Use of systemic corticosteroids for >14 days (use of topical or inhaled steroids is permitted) within the previous 6 months;</li>\n <li>\n Immunosuppressive, anti-cancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months.</li>\n <li>\n History of splenectomy.</li>\n <li>\n History of autoimmune disease</li>\n <li>\n Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions). (Note: a volunteer that states that he or she has easy bruising or bleeding but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience is eligible)</li>\n <li>\n History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, or clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow up).</li>\n <li>\n History of cancer (except basal cell carcinoma of the skin)</li>\n <li>\n Asthma that is not well controlled.</li>\n <li>\n History of allergic disease or reactions likely to be exacerbated by any component of the vaccine</li>\n <li>\n History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulty, angioedema).</li>\n <li>\n History of Guillain-Barre syndrome.</li>\n <li>\n Confirmed diagnosis of active or chronic hepatitis B, hepatitis C, active syphilis and/or active tuberculosis</li>\n <li>\n Seizure disorder: an individual who has had a seizure in the last 3 years is excluded (Not excluded: an individual with a history of seizures who has neither required medication nor had a seizure for three or more years).</li>\n <li>\n History of serious psychiatric conditions or any psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.</li>\n <li>\n Substance abuse disorder that precludes compliance with the protocol as assessed by the investigator.</li>\n <li>\n Any clinically significant acute or chronic medical condition that is considered unstable/progressive, or in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer’s ability to participate in the study</li>\n </ul>\n </li>\n <li>\n Abnormal clinically significant abnormal finding on screening biochemistry or haematology blood, or urinalysis, including but not limited to:</li>\n <li>\n <u>Haematology:</u>\n <ul>\n <li>\n Haemoglobin - <9.5 g/dl in females; <11.0 g/dl in males</li>\n <li>\n Absolute Neutrophil Count (ANC) – ≤1,000/mm3</li>\n <li>\n ï‚· Absolute Lymphocyte Count (ALC) – ≤650/mm3</li>\n <li>\n ï‚· Platelets - <100,000 cells/mm3</li>\n </ul>\n </li>\n </ul>\n</div>\n<div>\n <ul>\n <li>\n <u>Chemistry</u>\n <ul>\n <li>\n Creatinine >1.1 x upper limit of normal (ULN)</li>\n <li>\n AST >1.25 x ULN</li>\n <li>\n ALT >1.25 x ULN</li>\n </ul>\n </li>\n <li>\n Urinalysis\n <ul>\n <li>\n Clinically significant abnormal dipstick confirmed by microscopy:</li>\n <li>\n Protein = 2+ or more</li>\n <li>\n Blood = 2+ or more (not due to menses)</li>\n </ul>\n </li>\n <li>\n Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the study</li>\n <li>\n If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.</li>\n <li>\n NOTE: Investigators should ensure that all study enrolment criteria have been met at the end of the screening period. If a volunteer’s status changes at any time before the 1st dose of the study drug is given that they now meet an exclusion criterion, they should be excluded from participation in the study.</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • primary_end_points<div>\n PRIMARY</div>\n<div>\n Safety</div>\n<ul>\n <li>\n Proportion of volunteers with local and systemic reactogenicity events from Day 0 to Day 7 post vaccination</li>\n <li>\n Proportion of volunteers with Grade 3 or 4 unsolicited adverse events through 28 days post final vaccination</li>\n <li>\n Proportion of volunteers with vaccine related serious adverse events (SAEs) collected throughout the study period</li>\n</ul>\n<div>\n Immunogenicity</div>\n<ul>\n <li>\n Proportion of vaccine recipients developing HIV-1-specific T-cell responses</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity
      • trial_human_pharmacology1
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:208px;\">\n <p>\n <strong>Name</strong></p>\n </td>\n <td style=\"width:208px;\">\n <p>\n <strong>Designation</strong></p>\n </td>\n <td style=\"width:208px;\">\n <p>\n <strong>Qualifications </strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:623px;\">\n <p>\n <strong>Investigators</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Prof Eduard Sanders</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Principal Investigator</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n MD, MPH, PhD</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Eunice Nduati</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Research Scientist- Immunology</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BSc, MSc, PhD</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n <strong>Clinical team^a</strong></p>\n </td>\n <td style=\"width:208px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:208px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Dr Clara Agutu</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Medical Officer/Trial Clinician and Study Coordinator</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n MBChB, MPH, MSc</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Fredrick Ogadah</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Clinical Officer/ Trial Clinician</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Alex Thion’go</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Clinical Officer/ Trial Clinician</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:623px;\">\n <p>\n <strong>Pharmacy</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Jimmy Shangala</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Trial Pharmacist (Pharmacist of Record)</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BPharm</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Mwaganyuma Mwatasa</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Trial Pharmacist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BPharm</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Beatrice Wavinya</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Pharmaceutical Technologist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Andrew Guantai</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Pharmaceutical Technologist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:623px;\">\n <p>\n <strong>Regulatory</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Jennifer Kanungi</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Regulatory Affairs</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip, PG Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Esther Ndiangui</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Quality Officer</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n <strong>Administration </strong></p>\n </td>\n <td style=\"width:208px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:208px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Lucie Ikumi</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Project Administrator</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Brenda Nekesa</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Administrative Assistant/Reception</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:623px;\">\n <p>\n <strong>Community Engagement</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Evans Gichuru</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Community Liaison Officer</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BA</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Dancan Otieno</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Community Facilitator</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Khamisi Shilingi</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Research Counselor</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Alex Kigoro</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Research Counselor</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:623px;\">\n <p>\n <strong>Data Management </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Elizabeth Wahome</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Data Manager</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BSc, MSc</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Esther Yaa</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Senior Data Clerk</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Fanis Kiteki</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Data Clerk</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:623px;\">\n <p>\n <strong>Laboratory ^b </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Kelly Ramko</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Laboratory Manager</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BSc</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n John Mwambi</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Senior Laboratory Technologist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip, Higher Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Clara Karani</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Laboratory Technologist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n Margaret Nunah</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Laboratory Technologist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Dip</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:208px;\">\n <p>\n James Chemweno</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n Laboratory Technologist</p>\n </td>\n <td style=\"width:208px;\">\n <p>\n BSc</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n ^aSupported by the Clinical Trials Facility, Kilifi</p>\n<p>\n ^bSupported by the Clinical Trials Laboratory and Main KEMRI-Wellcome Trust Research Programme (KWTRP) laboratory in Kilifi</p>\n
      • other_details_explanation<div>\n The proposed regimen of ChAdOx1.tHIVconsv1 (C1) and MVA.tHIVconsv3 + MVA.tHIVconsv4 (M3M4) vaccines have not been tested together in humans before.</div>\n<div>\n However, MVA.tHIVconsv3 and MVA.tHIVconsv4 were administered to participants in the USA in a phase 1 pilot study to evaluate the safety and immunogenicity of the HIV-1 vaccines entitled ‘MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) in HIV-1-infected adults suppressed on Antiretroviral therapy – The M&M Study’ (NCT03844386). As of May 2020, 14 individuals have been enrolled in the study, 11 of whom have received either vaccinations of MVA.tHIVconsv3 or MVA.tHIVconsv4 alone or MVA.tHIVconsv3 and MVA.tHIVconsv4 together. Screenings and enrolments have been suspended, effective 9th March 2020 in light of current restrictions related to COVID-19.</div>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Medical and Healthcare products Regulatory Agency (MHRA), UK approval dated 30 Aril 2020</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationOne year
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo Normal Saline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites2
      • multi_country_listKenya, Uganda and Zambia
      • data_monitoring_committeeYes
      • total_enrolment_per_site22
      • total_participants_worldwide88
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePaola
      • investigator1_middle_name
      • investigator1_family_nameCicconi
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressThe Jenner Institute, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital, Old Road, Oxford, OX3 7LE, United Kingdom.
      • investigator1_telephone+44 (0)1865 611413
      • investigator1_emailpaola.cicconi@ndm.ox.ac.uk
      • organisations_transferred_Yes
      • number_participants44
      • notification
      • approval_date19-11-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-01-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonConditional approval provided until participants insurance cover is provided
      • final_report<p>\n <strong>HIV-CORE 006 Design Summary</strong></p>\n<p>\n HIV-CORE 006 was a double-blind placebo-controlled trial, in which the HIVconsvX mosaic immunogens were delivered by a prime-boost regimen of non-replicating simian adenovirus ChAdOx1 followed by non-replicating poxvirus MVA. Volunteers were randomised to receive either the vaccine regimen or placebo at 2 vaccination visits 4 weeks apart. The vaccine regimen consisted of a single mosaic prime ChAdOx1.tHIVconsv1 (C1) and a dual boost of MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) administered simultaneously in vaccine regimen C1-M3M4. The trial recruited healthy African adults 18-50 years of age, who were HIV-uninfected and at low risk of HIV infection.</p>\n<p>\n  </p>\n<p>\n 89 healthy men and women were randomised, 88 vaccinated to receive either the vaccine regimen or placebo in a ratio of 72:16 (figure 1):</p>\n<p style=\"margin-left:.5in;\">\n •           Vaccine Arm C1 prime followed by M3M4 boost at 4 weeks after enrolment; 72 vaccine recipients;</p>\n<p>\n •           Placebo Arm; 16 placebo recipients</p>\n<p>\n  </p>\n<p>\n To maintain blinding, all volunteers received two injections with half dose into the deltoid region of each arm of C1 or placebo at enrolment, and two injections of M3 or placebo into one deltoid region and M4 or placebo into the other) at 4 weeks after enrolment.</p>\n<p>\n  </p>\n<p>\n <img height=\"541\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image002.png\" width=\"416\" /></p>\n<p>\n <strong>Figure 1: CONSORT diagram</strong></p>\n<p>\n  </p>\n<p>\n <strong>Objectives</strong></p>\n<p>\n  </p>\n<p>\n <strong>PRIMARY</strong></p>\n<p>\n <strong>Safety</strong></p>\n<ul>\n <li>\n To evaluate the safety and tolerability of a prime boost vaccine regimen utilizing non-replicating simian adenovirus (ChAdOx1) followed by non-replicating poxvirus modified vaccinia virus Ankara (MVA) in adults in Eastern and Southern Africa</li>\n</ul>\n<p>\n <strong>Immunogenicity</strong></p>\n<ul>\n <li>\n To evaluate the specific T-cell immune responses induced by the ChAdOx1.tHIVconsv1 followed by MVA.tHIVconsv3&4 vaccines in vaccine recipients.</li>\n</ul>\n<p>\n <strong>SECONDARY</strong></p>\n<ul>\n <li>\n To assess tHIVconsvX-specific T-cell responses of for their frequency, breadth and duration in vaccine recipients.</li>\n <li>\n To assess functional T-cell responses in vaccine recipients that inhibit replication in vitro of viruses of major HIV-1 clades A, B, C and D.</li>\n</ul>\n<p>\n <strong>EXPLORATORY</strong></p>\n<ul>\n <li>\n To assess induction of plurifunctional tHIVconsvX-specific memory T cells in the vaccine recipients.</li>\n <li>\n Characterization of the gut microbiome composition and richness.</li>\n <li>\n Feasibility of recruiting required sample size across all sites within 16 weeks</li>\n <li>\n Feasibility of retaining at least 90% of enrolled volunteers to end of study.</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong>Research Ethics Committee and Regulatory Approvals </strong></p>\n<p>\n HIV-CORE 006 (NCT04553016) was a double-blind, randomized, placebo-controlled, first-in-man (parallel to HIV-CORE 005.2; NCT04586673), phase 1 clinical trial at four clinical sites in Uganda, Kenya, and Zambia. The study was sponsored by the University of Oxford (UOXF). Approvals for HIV-CORE 006 were granted as follows: MRC/UVRI and London School of Hygiene and Tropical Medicine (MUL) Uganda Research Unit, Masaka: approved by Uganda Virus Research Institute REC (GC/127/20/06/761), Uganda National Council for Science and Technology (HS844ES), and National Drug Authority (CTC 0171/2021); KEMRI-Wellcome Trust Research Programme (KWTRP), Kilifi: approved by Clinical Science Committee (CSC 180), KEMRI Scientific and Ethics Review Unit (SERU 4025) and Pharmacy and Poisons Board (PPB/ECCT/20/10/01/2021); Kenya AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi: approved by Kenyatta National Hospital University of Nairobi Ethics Research Committee (P863/10/2019), National Commission for Science, Technology & Innovation (NACOSTI/P/23/23155) and PPB (PPB/ECCT/20/06/09/2020); Center for Family Health Research Zambia (CFHRZ, formerly ZEHRP), Lusaka: approved by the University of Zambia Biomedical Research Ethics Committee (UNZABREC 495-2019) and Zambia Medicines Regulatory Authority (CT 098); and by Oxford Tropical Research Ethics Committee (OXTREC 56-19). The study was conducted according to the principles of the Declaration of Helsinki (2008) and complied with the International Conference on Harmonization Good Clinical Practice guidelines and Good Participatory Practices.</p>\n<p>\n  </p>\n<p>\n <strong>The study populations in Eastern and Southern Africa</strong></p>\n<p>\n The trial was activated at the CFHRZ-Lusaka site on 15 July 2021 and the final scheduled visit by the last participant was attended on 02November 2022. Each of the CRCs in Uganda, Kenya and Zambia carried out recruitment according to their site-specific recruitment plans in compliance with the protocol’s defined inclusion/exclusion criteria and conducted study visits according to protocol’s defined schedule of events. Together over the four CRCs, 186 subjects were screened for eligibility and 89 were  randomized and 88 dosed. The mean age of the participants was 31 years (range 19-50) and 57 (64%) were male. For the C1 vaccine, HIV-CORE 006 was the first-in-man study, which ran in parallel with the C1 dose escalation trial HIV-CORE 005.2 in the UK. Subjects were randomized to receive the standard doses of vaccines in regimen C1-M3M4 (n=72) or placebo (n=16). Standard vaccine doses were determined and used in previous trials of simian adenovirus and poxvirus-vectored vaccines. The follow-up period was 308 days after vaccination. The volunteer recruitment is summarized in table 1. Three participants (2 CFHRZ, 1 KAVI-ICR) were reported pregnant, 3 participants (following dosing) were terminated from the study of whom 1 (KEMRI) was Lost To Follow-up. There were 41 recorded protocol deviations, and 85 participants (22 from CFHRZ, 21 from KEMRI, 20 from KAVI-ICR and 22 from MUL) completed the study. Table 2 summarises the demographics.</p>\n<p>\n  </p>\n<p>\n <strong>Table 1: Recruitment by sites</strong></p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td>\n <p>\n <strong>Site</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Volunteers</strong></p>\n <p align=\"center\">\n <strong>screened</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Females</strong></p>\n <p align=\"center\">\n <strong>screened</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Males</strong></p>\n <p align=\"center\">\n <strong>screened</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Volunteers</strong></p>\n <p align=\"center\">\n <strong>screened out</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Volunteers</strong></p>\n <p align=\"center\">\n <strong>enrolled</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Females</strong></p>\n <p align=\"center\">\n <strong>enrolled</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Males</strong></p>\n <p align=\"center\">\n <strong>enrolled</strong></p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n MUL</p>\n </td>\n <td>\n <p align=\"center\">\n 47 (100%)</p>\n </td>\n <td>\n <p align=\"center\">\n 18 (38%)</p>\n </td>\n <td>\n <p align=\"center\">\n 29 (62%)</p>\n </td>\n <td>\n <p align=\"center\">\n 25 (53%)</p>\n </td>\n <td>\n <p align=\"center\">\n 22 (47%)</p>\n </td>\n <td>\n <p align=\"center\">\n 5 (11%)</p>\n </td>\n <td>\n <p align=\"center\">\n 17 (36%)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n KEMRI</p>\n </td>\n <td>\n <p align=\"center\">\n 50 (100%)</p>\n </td>\n <td>\n <p align=\"center\">\n 9 (18%)</p>\n </td>\n <td>\n <p align=\"center\">\n 41 (82%)</p>\n </td>\n <td>\n <p align=\"center\">\n 27 (54%)</p>\n </td>\n <td>\n <p align=\"center\">\n 23 (46%)</p>\n </td>\n <td>\n <p align=\"center\">\n 2 (4%)</p>\n </td>\n <td>\n <p align=\"center\">\n 21 (42%)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n KAVI-ICR</p>\n </td>\n <td>\n <p align=\"center\">\n 62 (100%)</p>\n </td>\n <td>\n <p align=\"center\">\n 32 (52%)</p>\n </td>\n <td>\n <p align=\"center\">\n 30 (48%)</p>\n </td>\n <td>\n <p align=\"center\">\n 34 (55%)</p>\n </td>\n <td>\n <p align=\"center\">\n 22 (35%)</p>\n </td>\n <td>\n <p align=\"center\">\n 14 (23%)</p>\n </td>\n <td>\n <p align=\"center\">\n 8 (13%)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n CFHRZ</p>\n </td>\n <td>\n <p align=\"center\">\n 27 (100%)</p>\n </td>\n <td>\n <p align=\"center\">\n 12 (44%)</p>\n </td>\n <td>\n <p align=\"center\">\n 15 (56%)</p>\n </td>\n <td>\n <p align=\"center\">\n 5 (19%)</p>\n </td>\n <td>\n <p align=\"center\">\n 22 (81%)</p>\n </td>\n <td>\n <p align=\"center\">\n 11 (41%)</p>\n </td>\n <td>\n <p align=\"center\">\n 11 (41%)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Total</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>186 (100%)</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>71 (38%)</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>115 (62%)</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>91 (49%)</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>89 (48%)</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>32 (17%)</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>57 (31%)</strong></p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n <strong>Table 2: Demographics</strong></p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td>\n <p>\n  </p>\n </td>\n <td>\n <p>\n  </p>\n </td>\n <td>\n <p align=\"center\">\n <strong>MUL</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>KEMRI</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>KAVI-ICR</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>CFHRZ</strong></p>\n </td>\n <td>\n <p align=\"center\">\n <strong>Overall 006</strong></p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Sex</p>\n </td>\n <td>\n <p>\n Male</p>\n </td>\n <td>\n <p align=\"center\">\n 17 (77%)</p>\n </td>\n <td>\n <p align=\"center\">\n 21 (91%)</p>\n </td>\n <td>\n <p align=\"center\">\n 8 (36%)</p>\n </td>\n <td>\n <p align=\"center\">\n 11 (50%)</p>\n </td>\n <td>\n <p align=\"center\">\n 57 (64%)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n  </p>\n </td>\n <td>\n <p>\n Female</p>\n </td>\n <td>\n <p align=\"center\">\n 5 (23%)</p>\n </td>\n <td>\n <p align=\"center\">\n 2 (9%)</p>\n </td>\n <td>\n <p align=\"center\">\n 14 (64%)</p>\n </td>\n <td>\n <p align=\"center\">\n 11 (50%)</p>\n </td>\n <td>\n <p align=\"center\">\n 32 (36%)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Age (years)</p>\n </td>\n <td>\n <p>\n Mean</p>\n </td>\n <td>\n <p align=\"center\">\n 29</p>\n </td>\n <td>\n <p align=\"center\">\n 34</p>\n </td>\n <td>\n <p align=\"center\">\n 27</p>\n </td>\n <td>\n <p align=\"center\">\n 34</p>\n </td>\n <td>\n <p align=\"center\">\n 31</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n  </p>\n </td>\n <td>\n <p>\n Range</p>\n </td>\n <td>\n <p align=\"center\">\n 19-39</p>\n </td>\n <td>\n <p align=\"center\">\n 27-50</p>\n </td>\n <td>\n <p align=\"center\">\n 19-37</p>\n </td>\n <td>\n <p align=\"center\">\n 24-47</p>\n </td>\n <td>\n <p align=\"center\">\n 19-50</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Height (cm)</p>\n </td>\n <td>\n <p>\n Range</p>\n </td>\n <td>\n <p align=\"center\">\n 148-190</p>\n </td>\n <td>\n <p align=\"center\">\n 163-182</p>\n </td>\n <td>\n <p align=\"center\">\n 154-186</p>\n </td>\n <td>\n <p align=\"center\">\n 150-185</p>\n </td>\n <td>\n <p align=\"center\">\n 148-190</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Body mass (kg)</p>\n </td>\n <td>\n <p>\n Range</p>\n </td>\n <td>\n <p align=\"center\">\n 46-91</p>\n </td>\n <td>\n <p align=\"center\">\n 41-84</p>\n </td>\n <td>\n <p align=\"center\">\n 46-106</p>\n </td>\n <td>\n <p align=\"center\">\n 45-98</p>\n </td>\n <td>\n <p align=\"center\">\n 45-106</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n <strong>The vaccine was well tolerated </strong></p>\n<p>\n Evaluation of the safety and tolerability of a prime-boost vaccine regimen was one of the trial’s primary objectives. Overall, all three vaccine components C1, M3 and M4 were well tolerated with no serious adverse events (SAEs) recorded. The most frequently reported AEs were those typically seen in response to viral vectored vaccines including pain at the injection site, headache, general malaise, fatigue, and myalgia. In line with data from clinical trials using similar vaccines, C1 tended to be less reactogenic (249/302 82% grade 1, 53/302 18% grade 2 and no grade 3) than M3M4 (172/310; 55% grade 1, 130/310; 41% and 8/310; 4% grade 3) (figure 2). All AEs resolved spontaneously within 72 hours. Placebo recipients recorded 31 local and 45 systemic AEs.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <img height=\"236\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image004.png\" width=\"314\" /></p>\n<p>\n <strong>Figure 2: Maximum severity of adverse events </strong></p>\n<p>\n Number of local (top) and systemic (bottom) solicited adverse events over 6 days after vaccine administration. The bars are colour-coded as indicated below the graphs according to the severity of the adverse events. P1 = the first administration of placebo; P2 – the second administration of placebo.</p>\n<p>\n Although expected, the relatively high frequency of solicited adverse reactions with the risk of severe (grade 3) symptoms triggered an ad-hoc safety meeting. The independent Data Monitoring and Ethics Committee (DMEC) reviewed the cases of two participants:</p>\n<ul>\n <li>\n One participant suffered severe headaches, malaise, fatigue and arthralgia following vaccination with MVA.tHIVconsv3 and MVA.tHIVconsv4. This was accompanied by a fever that peaked at 38.8 ËšC and associated with a severe lymphopenia 1 day after vaccination. He was managed symptomatically, including administration of paracetamol, and his symptoms subsided by day 2 after vaccination.</li>\n <li>\n A second participant suffered severe headaches, malaise, fatigue, myalgia and arthralgia following vaccination with MVA.tHIVconsv3 and MVA.tHIVconsv4. This was accompanied by a fever that peaked at 39.1 ËšC and symptoms of dyspepsia. She received symptomatic management that included administration of paracetamol. The severity of symptoms subsided by day 2 following vaccination when she reported that she had a mild headache but was able to function.</li>\n</ul>\n<p>\n  </p>\n<p>\n Considering the severity of symptoms, and the frequency with which they had occurred at the time among trial participants, the DMEC recommended that participants should receive a dose of anti-pyretic medications prior to administration of the MVA-vectored vaccines and should be advised to take additional doses of paracetamol, as required, over the following 24 to 48 hours.</p>\n<p>\n  </p>\n<p>\n Thirty-two participants reported 53 unsolicited adverse events (table 3). The majority was grade 1 to grade 2 in severity and all resolved without sequalae. Only three unsolicited adverse events were considered possibly related to vaccination, they resolved within 72 hours of onset and included mild fatigue and headache (11 days after the booster vaccination), moderate acute gastroenteritis (2 days after the first vaccination). They all occurred in the vaccination arm.</p>\n<p>\n  </p>\n<p>\n <strong>Table 3: Unsolicited Adverse Events Observed during the trial.</strong></p>\n<p>\n  </p>\n<table align=\"center\" border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"662\">\n <tbody>\n <tr>\n <td style=\"width:82px;height:44px;\">\n <p style=\"margin-left:5.25pt;\">\n Volunteer ID</p>\n </td>\n <td style=\"width:130px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n AE description</p>\n </td>\n <td style=\"width:90px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n Severity</p>\n </td>\n <td style=\"width:76px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n Onset days after vaccination</p>\n </td>\n <td style=\"width:71px;height:44px;\">\n <p>\n Days between onset and resolution</p>\n </td>\n <td style=\"width:94px;height:44px;\">\n <p style=\"margin-left:5.15pt;\">\n Relation to IP</p>\n </td>\n <td style=\"width:117px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n Outcome</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619004</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n ABNORMAL VAGINAL DISCHARGE SYNDROME</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 26</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 12</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:44px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619006</p>\n </td>\n <td style=\"width:130px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n UPPER RESPIRATORY TRACT INFECTION</p>\n </td>\n <td style=\"width:90px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:44px;\">\n <p>\n 16</p>\n </td>\n <td style=\"width:71px;height:44px;\">\n <p>\n 7</p>\n </td>\n <td style=\"width:94px;height:44px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:44px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619006</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n MALARIA</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 14</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 9</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619024</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n HEADACHE</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 24</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 10</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619024</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n CHILLS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 24</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 10</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619041</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n SOFT TISSUE INJURY</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 26</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619041</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n RIGHT ANKLE SPRAIN</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 26</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 8</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619042</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n UNSPECIFIC FEBRILE ILLNESS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 13</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n Unlikely</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00619047</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n TONSILLITIS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 20</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00621006</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n ARTHRITIS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 8</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:32px;\">\n <p style=\"margin-left:5.25pt;\">\n N00621006</p>\n </td>\n <td style=\"width:130px;height:32px;\">\n <p style=\"margin-left:5.3pt;\">\n BILATERAL LOWER LIMB MUSCLE PAINS</p>\n </td>\n <td style=\"width:90px;height:32px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:32px;\">\n <p>\n 15</p>\n </td>\n <td style=\"width:71px;height:32px;\">\n <p>\n 18</p>\n </td>\n <td style=\"width:94px;height:32px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:32px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:33px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622006</p>\n </td>\n <td style=\"width:130px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n COUGH</p>\n </td>\n <td style=\"width:90px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:33px;\">\n <p>\n 5</p>\n </td>\n <td style=\"width:71px;height:33px;\">\n <p>\n 7</p>\n </td>\n <td style=\"width:94px;height:33px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622019</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n UPPER RESPIRATORY TRACT INFECTION</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 5</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622027</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n VAGINAL CANDIDIASIS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 26</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 5</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622040</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n TOOTH ACHE</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 19</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622044</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n FATIGUE</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n Possible (Yes</p>\n <p style=\"margin-left:5.15pt;\">\n expected)</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622044</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n HEADACHE</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = mild</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 0</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n Possible (Yes</p>\n <p style=\"margin-left:5.15pt;\">\n expected)</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00622048</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n CELLULITIS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 10</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623003</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n HEADACHE</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 18</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:33px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623003</p>\n </td>\n <td style=\"width:130px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n UPPER RESPIRATORY TRACT INFECTION</p>\n </td>\n <td style=\"width:90px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = moderate</p>\n </td>\n <td style=\"width:76px;height:33px;\">\n <p>\n 23</p>\n </td>\n <td style=\"width:71px;height:33px;\">\n <p>\n 6</p>\n </td>\n <td style=\"width:94px;height:33px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:33px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623005</p>\n </td>\n <td style=\"width:130px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n ARTHRALGIA OF THE KNEES</p>\n </td>\n <td style=\"width:90px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = moderate</p>\n </td>\n <td style=\"width:76px;height:33px;\">\n <p>\n 12</p>\n </td>\n <td style=\"width:71px;height:33px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:94px;height:33px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:32px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623008</p>\n </td>\n <td style=\"width:130px;height:32px;\">\n <p style=\"margin-left:5.3pt;\">\n ACUTE ENTERITIS</p>\n </td>\n <td style=\"width:90px;height:32px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = moderate</p>\n </td>\n <td style=\"width:76px;height:32px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:71px;height:32px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:94px;height:32px;\">\n <p style=\"margin-left:5.15pt;\">\n Possible (Not Expected)</p>\n </td>\n <td style=\"width:117px;height:32px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623016</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n FLU LIKE ILLNESS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 3 = severe</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 26</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 8</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n Unlikely</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:33px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623017</p>\n </td>\n <td style=\"width:130px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n BILATERAL EYE PAIN</p>\n </td>\n <td style=\"width:90px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:33px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:71px;height:33px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:94px;height:33px;\">\n <p style=\"margin-left:5.15pt;\">\n Unlikely</p>\n </td>\n <td style=\"width:117px;height:33px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623021</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n PAIN AND DISCOLORATION AT VENEPUNCTURE SITE - RIGHT FOREARM</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 7</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:14px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623021</p>\n </td>\n <td style=\"width:130px;height:14px;\">\n <p style=\"margin-left:5.3pt;\">\n UPPER RESPIRATORY TRACT INFECTION</p>\n </td>\n <td style=\"width:90px;height:14px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:14px;\">\n <p>\n 20</p>\n </td>\n <td style=\"width:71px;height:14px;\">\n <p>\n 6</p>\n </td>\n <td style=\"width:94px;height:14px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:14px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623022</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n UPPER RESPIRATORY TRACT INFECTION</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n Unlikely</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623023</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n FLU LIKE ILLNESS</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 2 = Moderate</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 25</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:82px;height:29px;\">\n <p style=\"margin-left:5.25pt;\">\n N00623024</p>\n </td>\n <td style=\"width:130px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n HEADACHE</p>\n </td>\n <td style=\"width:90px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n 1 = Mild</p>\n </td>\n <td style=\"width:76px;height:29px;\">\n <p>\n 28</p>\n </td>\n <td style=\"width:71px;height:29px;\">\n <p>\n 11</p>\n </td>\n <td style=\"width:94px;height:29px;\">\n <p style=\"margin-left:5.15pt;\">\n No relationship</p>\n </td>\n <td style=\"width:117px;height:29px;\">\n <p style=\"margin-left:5.3pt;\">\n Resolved, no residual effects</p>\n </td>\n </tr>\n </tbody>\n</table>\n<div style=\"clear:both;\">\n  </div>\n<p>\n  </p>\n<p>\n One participant showed severe lymphopenia within 24 hours of the second vaccination.  The number of total lymphocytes dropped from 1000 to 350 lymphocytes per microliter of blood. Lymphocytes count recovered at the following appointment, and the participant was completely asymptomatic. Similar changes have been observed in other trials using the same vaccines and were considered an effect of peripheral lymphocytes migration to the lymph nodes rather than a true lymphopenia.  No other severe laboratory abnormalities detected. One participant had mild thrombocytopenia from baseline through the study; for this reason, it was considered not related to the vaccination with MVA vectored vaccines. Table 4 shows all the lab abnormalities observed during the HIV-CORE 006 trial.</p>\n<p>\n  </p>\n<p>\n <strong>Table 4: Lab abnormalities observed during the HIV-CORE 006 trial.</strong></p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong><img height=\"226\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image006.png\" width=\"601\" /></strong></p>\n<p>\n  </p>\n<p>\n In summary, the vaccines used in this clinical trial had an acceptable safety profile. The vast majority of the adverse events were expected and mild to moderate in nature. They all resolved within a few days without sequalae.</p>\n<p>\n  </p>\n<p>\n <strong>The HIVconsvX vaccination induced strong broadly specific T-cell responses</strong></p>\n<p>\n One of the primary objectives of the HIV-CORE 006 trial was to determine the proportion of vaccine recipients developing HIV-1-specific T-cell responses. The HIVconsvX-specific T cells induced by the vaccination were enumerated locally at each of the four CRCs using the same shared fresh IFN-g ELISPOT assay and reagents. For this objective, frequencies were compared before and after vaccination on days 0 and 35, respectively. Fresh ex vivo PBMCs were tested against 10 peptide pools P1 to P10 of 15-mer peptides overlapping by 11 amino acids corresponding to both mosaics of the entire HIVconsvX immunogens. Both the clinical and laboratory teams were blinded for the vaccine vs. placebo allocation. The C1-M3M4 vaccine regimen was highly immunogenic and increased HIV-1-specific responses in 70/71 (99%) analyzed recipients of the vaccine.</p>\n<p>\n The trial’s secondary objectives were to assess the magnitude, breadth, and duration of vaccine-elicited responses. These parameters were determined before vaccination (day 0), at peak of responses 1 week after M3M4 (day 35), and at the end of the study 40 weeks later (day 336). Across the four sites, HIVconsvX-specific T-cells peaked at median (range) 2,330 (80-16,750) SFU/10⁶ PBMC and recognized median (range) 8/10 (0-10) peptide pools (figure 3 and table 5). On average, these frequencies decreased 4·6-fold over the follow-up period. Responses in the placebo recipients were a median (range) 85 (10-460) SFU/10⁶ PBMCs.</p>\n<p>\n  </p>\n<p>\n  <img height=\"120\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image008.png\" width=\"581\" /></p>\n<p>\n <strong>Figure 3: Strong and broad T-cell responses induced in HIV-1-negative individuals by the HIVconsvX vaccines. </strong>Total frequencies determined in an IFN-g ELISPOT assay using HIVconsvX peptide pools P1-P10 corresponding to the two mosaics 1 and 2 of the vaccines on days 0, 35 and 308 shown for each of the four CRCs separately. Dunn’s multiple comparisons test was carried out, whereby the P values are: *** - 0.0001 to 0.001; and **** - <0.0001.</p>\n<p>\n  </p>\n<p>\n <strong>Table 5: Peak total magnitude and number of peptide pools out of 10 recognized by the HIVconsvX vaccines.</strong></p>\n<p>\n <img alt=\"A table with numbers and letters\n\nDescription automatically generated\" height=\"143\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image010.png\" width=\"460\" /></p>\n<p>\n  </p>\n<p>\n <strong>HIVconsvX vaccine-elicited T cells can proliferate and exert an effector function</strong></p>\n<p>\n Next, we examined the ‘stemness’ of the vaccine-induced memory cells, that is their ability to proliferate and function. Frozen PBMCs were cultured with individual peptide pools for 10 days and tested in an IFN-g ELISPOT assay against the pool’s peptide pairs (mosaic 1 and mosaic 2). A mean ± SD of 16 ± 18 and median (range) 13 (0-61) 15-mer peptide pairs stimulating ³750 SFU/10⁶ of cultured cells (corresponding to at least 30 SFU above no-peptide background in an assay well with 40,000 cells input) were recognized by the tested vaccine recipients (n=30). This number overestimates the real number targeted epitopes, which can be shared between overlapping 15/11 peptide pairs. All volunteers' tissue types for HLA class I and II were genetically determined for future detailed epitope characterizations (data under QC).</p>\n<p>\n  </p>\n<p>\n <strong>HIVconsvX-specific T cells inhibited viruses derived from four major global clades</strong></p>\n<p>\n Another trial’s secondary objective was to determine the breadth of inhibition of HIV-1 growth by vaccine-induced CD8⁺ T-cell effectors. A virus inhibition assay (VIA) employed infectious molecular clones (IMCs) of HIV-1, which originated from diverse countries and represented major global clades (table 6), maintained physiological levels and functions of the Nef protein, a negative regulatory factor which helps HIV-1 to evade immune responses, and produced the LucR enzyme to quantitate HIV-1 growth. Antigen non-specifically expanded CD8⁺ T-cell effectors were cocultured with IMC-infected volunteers’ autologous CD4⁺ cell targets for 5 days before the LucR activity in the cell lysates was quantified by emitting light. In preliminary results, the effectors demonstrated a broad cross-clade inhibition for most tested volunteers (table 7a-d). In essence, the HIVconsvX vaccination induced CD8⁺ T cells, which showed increased inhibition of median (range) 8 (0-8) IMCs at peak and 8 (0-8) at the end of the study relative to the pre-vaccination time point. While it is not certain how these VIA results translate into in vivo efficacy, they certainly encourage further vaccine development towards assessing clinical benefits it might offer.</p>\n<p>\n  </p>\n<p>\n <strong>Table 6. HIV-1 infectious clones (IMCs) used in VIA</strong></p>\n<p>\n <img alt=\"A table with black text\n\nDescription automatically generated\" height=\"130\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image012.png\" width=\"378\" /></p>\n<p>\n <strong>Table 7a: Cross-clade HIV inhibition in vitro – MUL</strong></p>\n<p>\n <img height=\"794\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image014.png\" width=\"625\" /></p>\n<p>\n  </p>\n<p>\n The 1st column shows ELISPOT data (Magn/Pools = total magnitude as SFU/10⁶ PBMC/Number of recognized pools). P – placebo. The data are shown as relative inhibition (please see Material and Methods). Dark red – inhibition relative to day 0 increased by more than ³1.0 log₁₀; medium red - inhibition relative to day 0 increased by <1.0 log₁₀ to ³0·1 log₁₀; light red - inhibition relative to day 0 increased by <0·1 log₁₀;  no colour – no increase in inhibition relative to pre-vaccination. nd – no data; ivg – insufficient virus growth.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Table 7b: Cross-clade HIV inhibition in vitro – KEMRI</strong></p>\n<p>\n <img height=\"826\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image016.png\" width=\"636\" /></p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Table 7c: Cross-clade HIV inhibition in vitro – KAVI-ICR</strong></p>\n<p>\n <img height=\"767\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image018.png\" width=\"599\" /></p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Table 7d: Cross-clade HIV inhibition in vitro – CFHRZ</strong></p>\n<p>\n <img height=\"697\" src=\"file:///C:/Users/jkanungi/AppData/Local/Temp/msohtmlclip1/01/clip_image020.png\" width=\"611\" /></p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Conclusion</strong></p>\n<p>\n  </p>\n<p>\n As per the trial’s primary endpoints, the C1, M3 and M4 vaccine components were safe and well tolerated, and induced HIVconsvX-specific responses in 70/71 (99%) recipients. The secondary endpoints demonstrated that the vaccine-elicited T-cells peaked at median (range) 2,330 (80-16,750) IFN-g spot-forming units/10⁶ PBMC, recognized 8 (0-10) out of ten peptide pools spanning the HIVconsvX regions, decreased 4·6-fold in magnitude over a six-month follow-up and inhibited HIV-1 derived from four major global clades A, B, C and D. Further T-cells characterizations are in progress with the aim to submit the manuscript for a publication in a high-impact peer-reviewed journal by the end of Q1 2024.</p>\n<p>\n Overall,, the results in sub-Saharan at-risk populations confirm the HIVconsvX vaccine regimen safety and immunogenicity demonstrated in the UK and encourage evaluation of the vaccine’s contribution to efficacy against HIV-1.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <br />\n  </p>\n<p>\n  </p>\n
      • implication_results
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        • id581
        • application_id937
        • given_nameEduard
        • middle_nameJ
        • family_nameSanders
        • qualificationMD, MPH, PhD
        • professional_addressKEMRI/ Wellcome Trust Research Programme, Hospital Road P.O. Box 230-80108 Kilifi, Kenya.
        • telephone+254 723593762
        • emailESanders@kemri-wellcome.org
        • created2020-09-11 09:57:42
        • modified2021-01-26 08:31:19
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        • id810
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        • site_nameKEMRI Mtwapa Research Clinic
        • physical_addressKEMRI/ Wellcome Trust Research Programme, Off Hospital Road, Kilifi
        • contact_detailsKEMRI/ Wellcome Trust Research Programme, Hospital Road P.O. Box 230-80108 Kilifi, Kenya.
        • contact_personProf Eduard Sanders
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          • created2012-05-31 16:15:49
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        • id811
        • application_id937
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        • site_nameKAVI-ICR Nairobi
        • physical_addressUniversity of Nairobi, Kenyatta National Teaching and Referral Hospital, Nairobi
        • contact_detailsUniversity of Nairobi, PO Box 19676-00202 Off Ngong Road, Nairobi Kenya
        • contact_personProfessor Walter Jaoko
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          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
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        • id454
        • application_id937
        • sponsorUniversity of Oxford, United Kingdom
        • sponsor_typeOthers
        • contact_personDr Paola Cicconi
        • addressThe Jenner Institute, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital, Old Road, Oxford. OX3 7LE United Kingdom
        • telephone_number+44 (0)1865 611413
        • fax_number
        • cell_number+44 (0)1865 611413
        • email_addresspaola.cicconi@ndm.ox.ac.uk
        • created2020-09-11 09:57:42
        • modified2021-01-26 08:31:19
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      • abstract_of_study<p>\n <strong>Background:</strong> While preventable, cervical cancer is the second most common cancer among women globally, accounting for approximately 600,000 new cases and 300,000 deaths per year. Due to lack of access to primary and secondary prevention, women living in low-and middle-income countries bear a disproportionate burden of cervical cancer, accounting for 90% of new cases and 85% of deaths globally. Cervical cancer can be prevented through vaccination against Human papillomavirus (HPV), whose infection is required to develop cervical cancer. Among unvaccinated women, screening for HPV or cervical precancer allows identification of precancerous lesions – primarily cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), that can be treated and cured, to prevent progression to cancer. Most CIN2/3 lesions that are left untreated will progress to invasive cervical cancer. Current treatments for CIN2/3 in both high- and low-resource countries (LMICs) require trained health care providers, who are often out of reach for many women, particularly in rural areas in LMICs. Lack of access to precancer treatment following screening in LMICs in part accounts for the high burden of incident cervical cancer. Preclinical data have demonstrated pro-apoptotic effects of Artesunate (AS), a commonly available drug with an excellent safety profile in oral, rectal and intravenous routes primarily used to treat malaria in LMICS. This led to a recent Phase I study in the United States that demonstrated that self-administered vaginal artesunate inserts (pessaries) are safe, well-tolerated, and demonstrate efficacy for treatment of CIN2/3. Based on the mechanism of action, the clinical safety profile, and widespread availability as a generic drug on the World Health Organization (WHO) List of Essential Medications, vaginal artesunate inserts (pessaries), if backed by data from randomized trials, may offer patient-controlled and access cervical precancer treatment method for women in LMICs who face the greatest burden of cervical cancer and have difficulty accessing skilled providers for precancer treatment. However, given that artesunate is a well-known drug used in malaria treatment, it is critical to ensure that vaginal application of the drug will not promote resistance for use in malaria treatment.</p>\n<p>\n <strong>     Objectives: </strong>The proposed study seeks to investigate the pharmacokinetics of Artesunate (AS) and dihydroartemisinin (DHA), the active metabolite of artesunate, following intravaginal use at the dosing and frequency being studied for cervical precancer treatment. A secondary objective is to investigate safety among study participants.</p>\n<p>\n <strong>            Methods: </strong>As a recent study demonstrated safety and tolerability of intravaginal artesunate among women with CIN2/3 and the safety of artesunate is well documented in numerous malaria studies, the proposed study will be conducted in female volunteers regardless of their HPV or cervical precancer disease status. In this single arm study, blood levels of DHA and artesunate following 5 daily applications of vaginal artesunate inserts (pessaries) will be measured. A sample size of twelve participants (N=12) are needed. Up to 16 will be consented to account for drop offs. Eligible participants will self-administer artesunate vaginal inserts (pessaries) daily in the study clinic for 5 days. Participants will undergo a blood draw prior to receiving the first dose of artesunate, and on day 5 before inserting the vaginal insert, and at 15 min, 30 mins, 1, 2, 4, 6, and 8 hours after. In each patient, pharmacokinetic parameters of artesunate and DHA will be calculated via quantitative analysis of with determination of maximum concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration versus time curve (AUC), apparent clearance, and elimination half-life (t1/2).</p>\n
      • study_title<p>\n <strong>IGHID 12333: Phase I study on the Pharmacokinetics of intravaginal, self-administered Artesunate vaginal pessaries among women in Kenya.</strong><strong>IGHID 12333: Phase I study on the Pharmacokinetics of intravaginal, self-administered Artesunate vaginal pessaries among women in Kenya.</strong></p>\n
      • laymans_summary<p>\n Cervical cancer, a disease of the cervix – the entrance of the womb is the second common cause of cancer in women around the world. Women in low- and middle-income countries like Kenya face the highest burden of cervical cancer. Cervical cancer is caused by human papillomavirus (HPV) infection. It can be prevented through vaccination against the HPV virus, and screening to find early changes in the cervix, called precancerous changes – scientifically called cervical intraepithelial neoplasia, which can be treated by a medical provider to prevent it from progressing to cancer. The HPV vaccines are new in Kenya and other low-income countries, and most women over 20 years of age have never been vaccinated. Screening for cervical cancer and treating precancerous lesions will prevent millions of unvaccinated women from getting diagnosed with cervical cancer. Current treatments for cervical precancer rely on a healthcare provider to perform them. In countries like Kenya and other LMICs where there are few nurses and doctors, many women found with precancer are often referred to far facilities to access treatment. Due to costs and other challenges, many women are unable to access referral centers with providers who can treat cervical precancer. Scientists are studying whether women with cervical precancer can use self-administered treatments with medications like a cream or pessary, to treat precancer, instead of relying on a health care provider to perform the treatment. One self-administered treatment being studied is a pessary formulation of the medication Artesunate, which is used to treat malaria in Africa and other places. A study in the United States has shown that Artesunate pessaries (vaginal inserts) are safe to use for precancer treatment, and ~ 70% women who used them were cured. Before Artesunate can be considered as a precancer treatment in Kenya and places like it, scientists need to understand whether using Artesunate as an intravaginal pessary can affect how it works to treat malaria – whether using it intravaginally can reduce its effect as a malaria treatment (developing resistance). This study is being done to investigate the blood levels of Artesunate when women use artesunate pessaries in the dosing being studied for cervical precancer. In other words, scientists are asking whether if a woman uses 200mg of artesunate pessary daily for five days, the medication can be found in the blood which could result in the medication being resistant to treating malaria. This is unlikely as the dosage used in the intravaginal pessary is much lower than the dosage used to treat malaria, and absorption of drugs in the vagina is much lower than when taken by mouth or used rectal – which is another way malaria drugs are given to children. To help answer this question of whether using low dose Artesunate pessaries for treating cervical precancer can cause resistance for malaria treatment, up to 16 female participants will be enrolled in this study. Study participants will use artesunate pessaries once daily for 5 days in the study clinic, and have blood drawn once on day 1 (prior to first pessary use), and six times on day 5 (last day of pessary use) to measure the artesunate drug levels in the blood. On day 5, participants will have a cannula placed and blood drawn from the cannula. The volume of blood drawn each time will be approximately 3 ml, less than a teaspoon. In comparison, when a person donates blood, approximately 500 ml of blood is drawn. The goal of this study is to confirm that artesunate pessaries can be used intravaginally for treatment of cervical precancer without creating resistance of the drug for treating malaria to enable studies on its use for precancer treatment.</p>\n
      • short_titleIGHID 12333
      • protocol_noECCT/24/02/04
      • version_no1.1
      • date_of_protocol04-01-2024
      • study_drugArtesunate 200mg Pessary
      • disease_conditionPharmacokinetics
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameArtesunate
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressgershonrota@gmail.com
      • applicant_covering_letter1
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      • applicant_signed_declaration1
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      • applicant_indemnity_cover1
      • applicant_opinion_letter1
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      • applicant_participating_countries(null)
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      • applicant_dsmb_charter1
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      • applicant_registration_ctr(null)
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      • declaration_applicantGreshon Rota
      • declaration_date108-02-2024
      • declaration_principal_investigatorChemta Mungo
      • declaration_date208-02-2024
      • placebo_presentNo
      • study_objectives<p>\n <strong>Primary Objective: </strong>To determine the area under the plasma concentration versus time curve (AUC) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya.</p>\n<p>\n  </p>\n<p>\n <strong>Secondary Objective</strong></p>\n<p style=\"margin-left:36.0pt;\">\n 1.      To determine the area under the plasma concentration versus time curve (AUC) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 2.      To determine the maximum concentration of Artesunate (AS) (Cmax) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 3.      To determine the maximum concentration of dihydroartemisinin (DHA) (Cmax) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 4.      To determine the time to maximum concentration (Tmax) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 5.      To determine the time to maximum concentration (Tmax) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 6.      To determine the half-life (t_1/2) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 7.      To determine the half-life (t_1/2) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 8.      To determine the apparent clearance (CL/F) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 9.      To determine the apparent clearance (CL/F) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 10.  To determine the volume of distribution (V/F) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p style=\"margin-left:36.0pt;\">\n 11.  To determine the volume of distribution (V/F) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya</p>\n<p>\n               12. To investigate the safety of 5-day course of self-administered intravaginal artesunate vaginal inserts (pessary) in women in Kenya</p>\n
      • principal_inclusion_criteria<p style=\"margin-left:36.0pt;\">\n -          Age 18 years to 65 years</p>\n<p style=\"margin-left:36.0pt;\">\n -          Negative pregnancy test at screening</p>\n<p style=\"margin-left:36.0pt;\">\n -          Weight ≥50 Kg at study entry*</p>\n<p style=\"margin-left:36.0pt;\">\n -          Willingness to use contraception (hormonal or barrier) during the 5-day study dosing phase if of childbearing age (less than 50 years of age)</p>\n<p style=\"margin-left:36.0pt;\">\n -          Ability and willingness to provide informed consent</p>\n<p style=\"margin-left:36.0pt;\">\n -          Plan to reside in the study location during the study period</p>\n<p style=\"margin-left:36.0pt;\">\n -          Agrees for samples without identifiers to be shipped outside of Kenya for testing</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:36.0pt;\">\n -          Current pregnancy or breastfeeding status</p>\n<p style=\"margin-left:36.0pt;\">\n -          History of total hysterectomy</p>\n<p style=\"margin-left:36.0pt;\">\n -          Known allergy to Artesunate</p>\n<p style=\"margin-left:36.0pt;\">\n -          Have a medical comorbidity that in the opinion of the investigator would interfere with study participation</p>\n<p style=\"margin-left:36.0pt;\">\n -          Currently receiving artemisinin-based agents for malaria treatment or completed artemisinin-based treatment within the previous 3 days.*</p>\n<p style=\"margin-left:36.0pt;\">\n -          Male at birth</p>\n<p style=\"margin-left:36.0pt;\">\n -          Current use of efavirenz antiretroviral therapy</p>\n<p style=\"margin-left:36.0pt;\">\n -          Positive malaria antigen test at screening</p>\n
      • primary_end_points<p>\n <u>Primary Endpoint:</u> Mean DHA AUC (ng*hr/ml) with standard deviation on Day 5. (DHA AUV= dihydroartemisinin area under curve)</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p style=\"margin-left:.75pt;\">\n <strong>The main study site is: </strong></p>\n<p style=\"margin-left:.1pt;\">\n FACES Building</p>\n<p style=\"margin-left:.1pt;\">\n Lumumba Sub-County Hospital</p>\n<p style=\"margin-left:.15pt;\">\n Along Ondiek Highway</p>\n<p style=\"margin-left:.4pt;\">\n Kisumu</p>\n<p style=\"margin-left:.2pt;\">\n The facility has</p>\n<p style=\"margin-left:19.3pt;\">\n 1. Reception and waiting bay</p>\n<p style=\"margin-left:18.35pt;\">\n 2. Six Clinic rooms</p>\n<p style=\"margin-left:18.5pt;\">\n 3. Pharmacy</p>\n<p style=\"margin-left:18.1pt;\">\n 4. Laboratory</p>\n<p style=\"margin-left:18.35pt;\">\n 5. Data room</p>\n<p style=\"margin-left:18.5pt;\">\n 6. Administration office</p>\n<p style=\"margin-left:18.2pt;\">\n 7. Open Office</p>\n<p style=\"margin-left:18.65pt;\">\n 8. Washrooms</p>\n<p style=\"margin-left:.4pt;\">\n All rooms are equipped with relevant furniture, equipment, and materials to facilitate the activities conducted in the rooms.</p>\n<p style=\"margin-left:.15pt;\">\n <strong><u>PERSONNEL </u></strong></p>\n<p style=\"margin-left:.15pt;\">\n <strong>Principal Investigators and role </strong></p>\n<p>\n <strong>Chemtai Mungo, MD, MPH</strong>: Dr. Chemtai Mungo will lead protocol implementation including bringing subject matter expertise, she will oversee all aspects of protocol implementation, and will lead data analysis, interpretation, dissemination of results, and future Phase II grant writing and implementation. </p>\n<p>\n  </p>\n<p>\n <strong>Jackton Omoto, MBChB, MMed</strong>, Maseno University (Co-Principal Investigator): Dr. Omoto  will lead protocol implementation and provide subject participant matter expertise, guidance on  recruitment and retention, as well as support in building capacity of providers to deliver the intervention. </p>\n<p style=\"margin-left:.55pt;\">\n <strong>Co-Investigators and roles  </strong></p>\n<p style=\"margin-left:.55pt;\">\n <strong>Cirillus Ogollah, BSc, DipCM, </strong>KEMRI (Co-Investigator): Mr. Ogollah will support  management of study field operations in Kenya, including supervision and support of the study  team, support the recruitment and enrollment strategies and support in the dissemination of results.</p>\n<p style=\"margin-left:.15pt;\">\n <strong>Greshon Rota, BPharm, KEMRI </strong>(Study Pharmacist): Dr. Rota will participate in  implementation of the study medicine and reporting of adverse effects. He will also act in liaison  with the regulatory authorities to ensure study follows clinical trials rules and regulations.</p>\n<p style=\"margin-left:.05pt;\">\n  </p>\n<p style=\"margin-left:.4pt;\">\n <strong>Other personnel: </strong></p>\n<p style=\"margin-left:.4pt;\">\n One Study Coordinator</p>\n<p style=\"margin-left:.4pt;\">\n One Study doctor</p>\n<p style=\"margin-left:.4pt;\">\n Two Research Assistants</p>\n<p style=\"margin-left:.4pt;\">\n One Data Analyst</p>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration4 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaLumumba subcounty Hospital Kisumu
      • single_site_physical_addressOndiek highway Kisumu
      • single_site_contact_personCirilus Ogollah
      • single_site_telephone0724717472
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site12
      • total_participants_worldwide12
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJackton
      • investigator1_middle_name
      • investigator1_family_nameOmoto
      • investigator1_qualificationMBCHB
      • investigator1_professional_addressMaseno University School of Medicine P.O.Box 3408, Kisumu, Kenya
      • investigator1_telephone+254721761484
      • investigator1_emailjomoto@maseno.ac.ke
      • organisations_transferred_No
      • number_participants12
      • notification
      • approval_date26-04-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted08-02-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been accepted.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-12 23:19:12
      • created2024-02-07 11:59:24
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1038
        • application_id1375
        • given_nameChemtai
        • middle_name
        • family_nameMungo
        • qualificationMD, MPH
        • professional_addressUniversity of North Carolina Chapel Hill School of Medicine Address: 3009 Old Clinic Building, Campus Box 7570, Chapel Hill, NC 27599
        • telephone+1-919-966-6049
        • emailChemtai_mungo@med.unc.edu
        • created2024-02-07 12:22:24
        • modified2024-02-08 05:21:58
    • SiteDetail(array)
      • 0(array)
        • id1670
        • application_id1375
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-02-07 12:22:24
        • modified2024-02-08 05:21:58
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id723
        • application_id1375
        • sponsorUniversity of North Carolina-Chapel Hill, Department of Obstetrics and Gynecology
        • sponsor_typeResearch Institution
        • contact_person
        • addressUniversity of North Carolina Chapel Hill School of Medicine Address: 3009 Old Clinic Building, Campus Box 7570, Chapel Hill, NC 27599
        • telephone_number+1-919-966-7564
        • fax_number
        • cell_number+1-919-966-7564
        • email_addressjenbren@med.unc.edu
        • created2024-02-07 12:22:24
        • modified2024-02-08 05:21:58
  • 3(array)
    • Application(array)
      • id319
      • user_id73
      • trial_status_id7
      • abstract_of_study<p>\n Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC/TDF) reduces the risk of HIV-1 acquisition in high-risk HIV-1-uninfected adults.<a href=\"#_ENREF_1\" title=\"Baeten, 2012 #33\">^1-4</a>  Clinical trials have demonstrated protection efficacies of 44-75% in randomized comparisons to placebo and ~90% in case-control analyses of participants with high PrEP adherence. On the basis of these data, the US Food and Drug Administration (FDA) approved the use of FTC/TDF for PrEP in July 2012<a href=\"#_ENREF_5\" title=\", 2012 #158\">⁵</a>. The World Health Organization also issued guidance on oral PrEP, specifically for heterosexual HIV-1 serodiscordant couples and men and transgender women who have sex with men, regarding use in the context of demonstration projects to garner additional information to facilitate policies about PrEP implementation<a href=\"#_ENREF_6\" title=\"WHO, 2012 #157\">⁶</a>. In addition, the US Centers for Disease Control and Prevention (CDC) issued interim guidance for clinicians considering using PrEP for prevention of HIV-1 infection in high-risk heterosexually active adults<a href=\"#_ENREF_7\" title=\"CDC, #361\">⁷</a>, and identified the need for data on infant safety during pregnancy and postpartum breastfeeding for heterosexual women using FTC/TDF to prevent acquisition of HIV-1. The risk of HIV-1 acquisition is increased two-fold in women during pregnancy and the early post-partum period<a href=\"#_ENREF_8\" title=\"Mugo, 2011 #291\">⁸</a>, and thus PrEP could be an important strategy to reduce risk of HIV-1, if demonstrated to be safe.  Accordingly, it is important to assess whether FTC/TDF when used as PrEP by lactating mothers is excreted into breast milk and absorbed by the nursing infant in biologically significant concentrations. Determining the concentration of FTC/TDF infants are exposed to and subsequently absorbed via breast milk when taken daily as PrEP by lactating women is needed to evaluate the benefits and risks of maternal FTC/TDF PrEP use during lactation. Specially, the concentration of FTC and TDF excreted into and absorbed by nursing infants via breast milk of lactating women using FTC/TDF PrEP for HIV-1 prevention has not been studied. This protocol describes an  interventional, open-label, single-arm, repeat-dose study among heterosexual HIV-1 uninfected lactating women to determine the magnitude and extent of infant exposure to daily FTC/TDF via maternal breast milk when taken over one week as PrEP by lactating women. </p>\n<p>\n <strong>Design:   </strong>Interventional, open-label, single-arm, repeat-dose, pharmacokinetic study Up to 10 days of follow-up per mother-infant pairs</p>\n<p>\n <strong>Population:  </strong>HIV-1 uninfected lactating mother-infant pairs</p>\n<p>\n <strong>Study Site:  </strong>Thika, Kenya and Kampala, Uganda Partners PrEP Study sites</p>\n<p>\n <strong>Approach:  </strong>We will enroll up to 50 mother-infant pairs to characterize infant drug absorption for infant ages 0-24 weeks postpartum. We will conduct quantitative analyses to describe the magnitude and extent of infant exposure to FTC/TDF PrEP through breast milk when used by lactating women.</p>\n<p style=\"margin-left:63.0pt;\">\n <strong>Specific Aim:</strong></p>\n<p>\n To quantify the steady state concentrations of tenofovir (TFV) and emtricitabine (FTC) in infant plasma after FTC/TDF PrEP exposure through maternal breast milk.</p>\n<p>\n Decisions about the safety of breast feeding during maternal ingestion of drugs require knowledge of the amount of drug which might be present in breast milk. Understanding the concentration of FTC/TDF infants are exposed to and subsequently absorbed via breast milk when taken as PrEP by lactating women is needed to permit a thorough evaluation of the benefits and risks of maternal FTC/TDF PrEP use during lactation. We will measure infant plasma, maternal plasma, and breast milk FTC and TFV concentrations in an open-label, repeat dose study of daily FTC/TDF PrEP among HIV-1-uninfected lactating mother-infant pairs.</p>\n<p>\n <em>The primary outcomes of this study will be the steady state infant plasma FTC and TFV levels, infant plasma to maternal breast milk FTC and TFV concentration ratios, and maternal breast-milk to plasma FTC and TFV concentration ratio. A single infant plasma sample will be collected after the maternal 7^th PrEP dose. M</em><em>aternal plasma and breast-milk samples each will be collected for trough and peak levels immediately before administration of the 7^th and 10^th doses and 1-2 hours after the 7^th and 10^th doses, respectively.</em></p>\n
      • study_title<p>\n <strong>An open-label, short-duration, repeat-dose study of breast milk excretion and infant absorption of daily oral Tenofovir Disoproxil Fumarate/Emtricitabine when used by HIV-1 uninfected lactating women </strong></p>\n
      • laymans_summary<p>\n Other research studies have found that pregnant women who take the Truvada® medication do not have increased risks of serious problems with their pregnancy and their babies do not have serious birth defects. More research studies in HIV-uninfected women who are taking Truvada® medication during pregnancy and breast feeding are needed. The purpose of this study is to find out more about using Truvada® during breast feeding. Specifically, this research will study the amount of Truvada® drugs that are transferred into breast milk and then absorbed by the nursing baby when Truvada® is used by breast feeding women as PrEP.</p>\n
      • short_titleBreast Feeding Study
      • protocol_noECCT/14/09/03
      • version_no1.0
      • date_of_protocol08-08-2014
      • study_drugTenofovir Disoproxil Fumarate/Emtricitabine (Truvada)-Breast Feeding Study
      • disease_conditionNone
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameTenofovir Disoproxil Fumarate/Emtricitabine (Truvada)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRwamba@csrtkenya.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Kenneth Ngure
      • declaration_date115-09-2014
      • declaration_principal_investigatorDr. Nelly Rwamba Mugo
      • declaration_date215-09-2014
      • placebo_presentNo
      • study_objectives<p style=\"margin-left:63.0pt;\">\n  </p>\n<p>\n <span style=\"font-size:12px;\">To quantify the steady state concentrations of tenofovir (TFV) and emtricitabine (FTC) in infant plasma after FTC/TDF PrEP exposure through maternal breast milk.</span></p>\n
      • principal_inclusion_criteria<p style=\"margin-left: 0.5in;\">\n For infant’s mother and father          </p>\n<p style=\"margin-left:.5in;\">\n -  Able and willing to provide informed consent for the infant to participate in the study</p>\n<ul>\n <li>\n Of legal age ≥18 years to consent</li>\n</ul>\n<p>\n For HIV-1 uninfected mother, in addition to the criteria noted immediately above:</p>\n<ul>\n <li>\n Willing to provide breast milk samples and breastfeed during the duration of the study 0-24 weeks postpartum</li>\n <li>\n Breastfeeding an infant</li>\n <li>\n HIV-1 uninfected based on negative HIV-1 rapid tests, both at study screening and at the enrollment visit </li>\n <li>\n Adequate renal function, defined by normal creatinine levels and estimated creatinine clearance ≥60 mL/min</li>\n <li>\n Not infected with hepatitis B virus, as determined by a negative hepatitis B surface antigen test</li>\n <li>\n Not currently using PrEP</li>\n <li>\n Enrollment of individuals with active and serious infections or active clinically significant medical problems will be at the discretion of the site investigator</li>\n <li>\n <em>Note: single mothers are eligible to participate in this study. Where possible the father’s permission will be obtained. When the father is unknown, incompetent, deceased, or not reasonably available, or when only the mother has the legal responsibility for the care and custody of the child, the infant participant will be based on the mother’s consent and documentation will be added to file.</em></li>\n</ul>\n<p>\n For infant</p>\n<ul>\n <li>\n Infant born to eligible women</li>\n <li>\n Age 0-24 weeks</li>\n <li>\n Otherwise infant has no serious infections or active clinically significant medical problems</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Women breastfeeding more than one child</li>\n <li>\n  Preterm babies or infants with low birth weight (i.e. ≤2000mg)</li>\n</ul>\n
      • primary_end_points<p>\n The primary outcomes of this study will be the steady state infant plasma FTC and TFV levels, infant plasma to maternal breast milk FTC and TFV concentration ratios, and maternal breast-milk to plasma FTC and TFV concentration ratio. A single infant plasma sample will be collected after the maternal 7^th PrEP dose. Maternal plasma and breast-milk samples each will be collected for trough and peak levels immediately before administration of the 7^th and 10^th doses and 1-2 hours after the 7^th and 10^th doses, respectively.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyDetermining the steady state infant plasma FTC and TFV levels, infant plasma to maternal breast milk FTC and TFV concentration ratios, and maternal breast-milk to plasma FTC and TFV concentration ratio.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Thika partners in Prevention, Site has 32 full time clinical trial staff (including physicians, nurses, counsellors, pharmacists).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Principal Investigator: Dr. Nelly R. Mugo  MBChB,MMED,MPH</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Study coordinator: Dr. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Lead Physician for the study: Dr. Gabriel Muthuri  MBChB</p>\n
      • other_details_explanation<p>\n More than 2.5 million persons are infected with HIV-1 annually, the majority in sub-Saharan Africa, the region with the highest prevalence. In sub-Saharan Africa, the majority of new HIV-1 infections occur in women of childbearing age.Pregnancy and postpartum breastfeeding represent periods of heightened HIV-1 risk for women and for their infant if acute HIV-1 infection occurs. HIV-1 uninfected women who desire pregnancy with a partner who is HIV-1 infected or at high risk of being infected require protective strategies for themselves and their future children. Novel, effective HIV-1 prevention strategies remain urgently needed, particularly those that are deliverable to and useable by high-risk populations. Daily oral pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition^,peri-coitally dosed tenofovir gel, and antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons are the most promising new approaches for decreasing HIV-1 spread.  These antiretroviral-based strategies provide an HIV-1 prevention option for women who desire conception or pregnancy and that is under their control; other available HIV-1 prevention strategies of condoms and abstinence, do not allow for conception.</p>\n
      • other_details_regulatory_notapproved<p>\n University of Washington, IRB</p>\n<p>\n    Applications made on 01 September 2014</p>\n
      • other_details_regulatory_approved<p>\n Kenya Medical Research Institute, Ethical Review Committee.</p>\n<p>\n Approved Study on 25 August 2014</p>\n<p>\n Single site each  in both  Kenya and Uganda</p>\n
      • other_details_regulatory_rejected<p>\n None.</p>\n
      • other_details_regulatory_halted<p>\n None.</p>\n
      • estimated_duration1 year
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaPartners in Prevention, Thika Site
      • single_site_physical_addressOAU Road, Near Thika Nursing Home
      • single_site_contact_personDr. Kenneth Ngure
      • single_site_telephone067-22561
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listKenya\nUganda
      • data_monitoring_committeeNo
      • total_enrolment_per_site25-30 Mother Infant pairs
      • total_participants_worldwide50 Mother Infants pairs
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameKenneth
      • investigator1_middle_nameKiggundu
      • investigator1_family_nameMugwanya
      • investigator1_qualificationMBChB, MPH
      • investigator1_professional_address325 Ninth Avenue, UW Box 359927 Seattle, WA 98104
      • investigator1_telephone+1 206 859 3578
      • investigator1_emailmugwanya@uw.edu
      • organisations_transferred_Yes
      • number_participants25-30 Mother Infant pairs
      • notification
      • approval_date19-08-2015
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-12-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2020-12-17 14:59:38
      • created2014-08-25 16:04:55
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id228
        • application_id319
        • given_nameJared
        • middle_nameMurray
        • family_nameBaeten
        • qualificationMD, PhD
        • professional_address325 Ninth Avenue, Seattle, WA 98104
        • telephone+1 206 520 3808
        • emailjbaeten@u.washington.edu
        • created2014-08-25 16:14:12
        • modified2020-12-17 14:59:38
      • 1(array)
        • id229
        • application_id319
        • given_nameNelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBChB, MPH
        • professional_addressUNITID Building, Box 19865-00202, KNH, Nairobi
        • telephone0723 914057
        • emailrwamba@csrtkenya.org
        • created2014-09-03 15:16:38
        • modified2020-12-17 14:59:38
    • SiteDetail(array)
      • 0(array)
        • id270
        • application_id319
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2014-08-25 16:14:12
        • modified2020-12-17 14:59:38
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id177
        • application_id319
        • sponsorUniversity of Washington
        • sponsor_typeResearch Institution
        • contact_personDr. Nelly R. Mugo
        • addressUNITID Building, Box 19865-00202, KNH, Nairobi
        • telephone_number067-22561
        • fax_numberN/A
        • cell_number0723 914057
        • email_addressrwamba@csrtkenya.org
        • created2014-08-25 16:14:12
        • modified2020-12-17 14:59:38
  • 4(array)
    • Application(array)
      • id143
      • user_id21
      • trial_status_id5
      • abstract_of_study<p>\n Schema Attached as a separate PDF document</p>\n
      • study_title<p>\n <strong>A5225</strong><strong>/HiFLAC</strong>: <strong>A Phase I/II Dose-Finding Study of High-Dose Fluconazole Treatment in AIDS-Associated Cryptococcal Meningitis</strong></p>\n
      • laymans_summary(null)
      • short_titleHigh-Dose Fluconazole Treatment in AIDS-Associated CM
      • protocol_noECCT/10/03/03
      • version_no2.0
      • date_of_protocol11-05-2012
      • study_drugFluconazole
      • disease_conditionCryptococcal Meningitis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameDiflucan
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaksudoi@hotmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantAllan K Sudoi
      • declaration_date107-06-2013
      • declaration_principal_investigatorAbraham M Siika, MBChB, MMed, Msc - Site Principal Investigator
      • declaration_date207-06-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h3>\n Inclusion Criteria – Step 1</h3>\n<ol>\n <li>\n Cryptococcal meningitis documented either by a positive CSF cryptococcal culture, a positive CSF India ink preparation, or a positive CSF cryptococcal antigen latex agglutination test within 7 days prior to entry.</li>\n <li value=\"2\">\n CSF collection for quantitative cryptococcal culture within 72 hours prior to study entry or planned to be performed at study entry.</li>\n <li value=\"3\">\n HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by or within 10 days after study entry by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: The term ‘licensed’ refers to an FDA-approved kit which is required for all IND studies. For non-US sites, ‘licensed’ refers to a kit that has been certified or licensed by an oversight body within that country and that has been validated internally. However, non-US sites are encouraged to use FDA-approved methods for IND studies.</p>\n<p style=\"margin-left:72.0pt;\">\n The World Health Organization and the US Centers for Disease Control and Prevention guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.</p>\n<ol>\n <li value=\"4\">\n Men and women age ³ 16 years.</li>\n <li value=\"5\">\n Ability to take oral medications.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Administration of fluconazole tablets via nasogastric tube is permitted.</p>\n<ol>\n <li value=\"6\">\n For patients with a co-morbid complication of HIV, including opportunistic infections, receipt of stable treatment for the co-morbid complication and clinically stable, as judged by the site investigator. </li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Stable treatment is defined as treatment that has been taken for at least 2 weeks without change in dose or formulation of any of its components.</p>\n<ol>\n <li value=\"7\">\n For female participants of reproductive potential (defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or have not undergone surgical sterilization [eg, hysterectomy, or bilateral oophorectomy or salpingotomy]) a negative serum or urine pregnancy test result must be obtained within 2 days prior to study entry.</li>\n <li value=\"8\">\n All participants must agree not to participate in the conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).</li>\n <li value=\"9\">\n If participating in sexual activity that could lead to pregnancy, female study participants must agree to the simultaneous use of two forms of contraceptive (from the list below) during such sexual activity, and male study participants must agree to use a condom during such sexual activity. This requirement continues while the study participant is on study treatment and for 6 weeks after fluconazole has been discontinued.</li>\n</ol>\n<ul>\n <li>\n Condoms (male or female) with or without a spermicidal agent</li>\n <li>\n Diaphragm or cervical cap with spermicide</li>\n <li>\n IUD (intrauterine device)</li>\n <li>\n Injectable DepoProvera</li>\n <li>\n Tubal ligation</li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Use of oral hormone-based contraceptives is prohibited while a study participant is taking any study-provided fluconazole.</p>\n<ol>\n <li value=\"10\">\n Study participants who are not of reproductive potential (defined as women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization [eg, hysterectomy, or bilateral oophorectomy or salpingectomy], or men who have documented azoospermia), are eligible without the requirement to use contraceptives.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Lack of reproductive potential requires written documentation or oral communication from a clinician or clinician’s staff documented in source documents.</p>\n<ol>\n <li value=\"11\">\n Willingness and ability to adhere to dose schedules and mandatory procedures.</li>\n <li value=\"12\">\n Measured or calculated creatinine clearance of ≥50 mL/min within 3 days prior to study entry.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n A calculator is available at the Data Management Center at <a href=\"https://www.fstrf.org/ACTG/\">https://www.fstrf.org/ACTG/</a> or at <a href=\"http://www.fstrf.org/ACTG/index.html\">http://www.fstrf.org/ACTG/index.html</a>.</p>\n<ol>\n <li value=\"13\">\n The following laboratory values within 3 days prior to study entry:</li>\n</ol>\n<ul>\n <li>\n aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 5 X the upper limit of normal (ULN)</li>\n <li>\n total bilirubin ≤ 2.5 X ULN</li>\n <li>\n absolute neutrophil count (ANC) ≥ 750/mm³</li>\n <li>\n platelet count ≥ 50,000/mm³</li>\n <li>\n hemoglobin ³ 7.0 g/dL</li>\n</ul>\n<ol>\n <li value=\"14\">\n Ability and willingness of the participant or legal guardian/representative to give informed consent.</li>\n <li value=\"15\">\n Availability at the site of at least 2 weeks of its standard of care ampho B-based regimen.</li>\n</ol>\n<h3>\n Inclusion Criteria – Step 2</h3>\n<ol>\n <li>\n Randomization to an ampho B-based regimen in Step 1.</li>\n <li value=\"2\">\n Receipt of at least one dose of ampho B-based regimen in Step 1.</li>\n <li value=\"3\">\n Premature discontinuation of ampho B in response to the occurrence of any treatment-limiting toxicity, as described in section 5 of the A5225/HiFLAC MOPS.</li>\n</ol>\n<h3>\n Inclusion Criteria - Step 3</h3>\n<ol>\n <li>\n For participants in Step 1 who are currently receiving study-provided fluconazole, with no plans to discontinue study treatment, a negative CSF culture after 2 weeks incubation from a sample obtained at or before week 6 (days 35-49).</li>\n <li value=\"2\">\n For participants in Step 1 who are currently receiving an ampho B-based regimen or alternative treatment, completion of approximately 2 weeks of treatment.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: The total amount of ampho B received by a participant is expected to be approximately 8.4 mg/kg.</p>\n<ol>\n <li value=\"3\">\n For participants in Step 2 who are currently receiving study-provided fluconazole, with no plans to discontinue study treatment, negative CSF culture after 2 weeks incubation from a sample obtained at or before week 6 (day 35-49).</li>\n</ol>\n<h3>\n Inclusion Criteri<strong>on</strong> – Step 4</h3>\n<ol>\n <li>\n On study treatment at week 10 (day 63-77)<strong>, with no plans to discontinue study treatment</strong></li>\n</ol>\n<p>\n  </p>\n
      • principal_exclusion_criteria<h3>\n Exclusion Criteria - Step 1</h3>\n<ol>\n <li>\n Expected survival of ≤ 2 weeks, in the opinion of the site investigator and, if available, the primary care provider.</li>\n <li value=\"2\">\n For patients with a co-morbid complication of HIV, anticipated difficulty, in the opinion of the site investigator, in judging response to study treatment as a result of the co-morbid complication or the drugs used to treat it.</li>\n <li value=\"3\">\n Breastfeeding.</li>\n <li value=\"4\">\n A prior episode of CM, either as indicated by patient or as noted in patient medical records.</li>\n <li value=\"5\">\n Use of any of the following drugs, within the time periods described:</li>\n</ol>\n<ul>\n <li>\n any ARV within 30 days prior to study entry</li>\n <li>\n rifampin within 2 weeks prior to study entry, when enrollment is open to a cohort with an induction dose of fluconazole of 1200 mg daily (NOTE: this exclusion does not apply to participants who are enrolled at higher induction doses of fluconazole even if they have their individual dose reduced to 1200mg daily fluconazole based on their weight at study entry)</li>\n <li>\n warfarin within 3 days prior to study entry</li>\n <li>\n terfenadine or cisapride within 24 hours prior to study entry</li>\n <li>\n other drugs known to interact with fluconazole, the co-administration of which may lead to life-threatening side effects, within 10 days prior to study entry (see section 3 of the current A5225/HiFLAC MOPS)</li>\n <li>\n drugs that may decrease the effect of fluconazole, or whose co-administration may increase their own toxicity or decrease their own efficacy, within 24 hours prior to study entry (see section 3 of the current A5225/HiFLAC MOPS)</li>\n <li>\n phenytoin, carbamazepine, cyclosporin A, tacrolimus, sirolimus, astemizole, or long-acting barbiturates within 7 days prior to study entry</li>\n <li>\n more than 72 cumulative hours of systemic treatment with any antifungal for any reason within 14 days prior to study entry.</li>\n</ul>\n<ol>\n <li value=\"6\">\n Suspected or active tuberculosis (TB), even if untreated, for participants screening at the time that a 1200 mg daily fluconazole induction cohort is enrolling. A chest x-ray may be used to confirm suspected tuberculosis, but is not required.</li>\n <li value=\"7\">\n Known allergy, sensitivity to, or intolerance of fluconazole or other imidazole or triazole compounds, or to ampho B or other components of the standard of care ampho-B based regimen.</li>\n <li value=\"8\">\n History of clinically significant cardiac disease, in opinion of site investigator, including symptoms of ischemia, coronary artery disease, congestive heart failure, or arrhythmia.</li>\n <li value=\"9\">\n ECG (electrocardiogram) with QTc interval greater than 450 msec within 7 days prior to study entry.</li>\n <li value=\"10\">\n History of CNS disorder (excluding mood disorders) or concurrent CNS disorder(s) that, in the opinion of the investigator, would interfere with assessment of efficacy (e.g., ability to perform CSF sampling) such as lymphoma, neurocysticercosis, or toxoplasmosis.</li>\n <li value=\"11\">\n Receipt of investigational drug therapy within 30 days prior to study entry without prior approval of the A5225/HiFLAC core team.</li>\n <li value=\"12\">\n Receipt of any of the following for treatment of the current episode of CM:</li>\n</ol>\n<ul>\n <li>\n more than 1200 mg of fluconazole cumulative</li>\n <li>\n more than 1.5 mg/kg of ampho B cumulative</li>\n <li>\n more than 750 mg/kg of flucytosine cumulative</li>\n <li>\n more than 72 cumulative hours of any systemic antifungal therapy</li>\n</ul>\n<ol>\n <li value=\"13\">\n Active drug or alcohol use, dependence, or other conditions that in the opinion of the site investigator would jeopardize the safety of a participant in the study or would render the person unable to comply with the study plan.</li>\n</ol>\n<h3>\n Exclusion Criteria – Step 2</h3>\n<ol>\n <li>\n Receipt of fluconazole monotherapy in Step 1.</li>\n <li value=\"2\">\n Receipt of ≥8.4 mg/kg ampho B.</li>\n <li value=\"3\">\n At or beyond Day 17 in Step 1.</li>\n</ol>\n<h3>\n Exclusion Criteria – Step 3</h3>\n<ol>\n <li>\n On study treatment beyond week 10 (day 77) in Step 1 or Step 2.</li>\n <li value=\"2\">\n Currently off study treatment.</li>\n</ol>\n<h3>\n Exclusion Criterion – Step 4</h3>\n<ol>\n <li>\n Currently off study treatment</li>\n</ol>\n
      • primary_end_points<p>\n <strong>Primary Outcomes</strong></p>\n<ol>\n <li>\n Discontinuation of fluconazole or ampho B, including precipitating and surrounding adverse events.</li>\n <li value=\"2\">\n Qualitative and quantitative CSF culture results at entry, week 2, and when conducted thereafter.</li>\n <li value=\"3\">\n Survival.</li>\n</ol>\n<p>\n <strong>Secondary Outcomes</strong></p>\n<ol>\n <li>\n Results of the neurological examination (at study entry and at weeks 2, 10, 24, at progression of symptoms, and at the time of premature treatment or study discontinuation) and of functional status evaluation (prior to onset of current CM illness, at study entry, at week 10, and at time of premature treatment or study discontinuation).</li>\n <li value=\"2\">\n Length of hospitalization and number and nature of hospital readmissions.</li>\n <li value=\"3\">\n Recurrence/relapse of CM based on clinical presentation.</li>\n <li value=\"4\">\n CNS IRIS.</li>\n <li value=\"5\">\n Additional safety parameters including: Grade 3 and 4 adverse events; dose modifications; duration of temporary treatment interruptions; permanent discontinuation of either agent.</li>\n</ol>\n<p>\n <strong>Exploratory Outcomes (to be described in separate analysis plans)</strong></p>\n<ol>\n <li>\n Pharmacology</li>\n <li value=\"2\">\n Antifungal drug susceptibility of cryptococcal isolates.</li>\n <li value=\"3\">\n Ability of LFCrAg assay to detect cryptococcal antigen in stored urine, serum, plasma, and CSF.</li>\n</ol>\n<p>\n  </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Abraham M. Siika MBChB, MMed, MS- Site Leader/ Principal Investigator</p>\n<p>\n David Kiplimo Lagat- MBChB, MMed- Investigator</p>\n<p>\n Charles Kwobah, MBChB- Medical Officer</p>\n<p>\n Mercy Karoney MBChB- Medical Officer</p>\n<p>\n Simon Wachira Njuguna, B Pharm, MPSK - Pharmacist of Record</p>\n<p>\n Kipruto Kirwa, BSc, MPH, PhD- Quality Manager</p>\n<p>\n Priscilla Cheruiyot, BScN, MPH- Site Coordinator</p>\n<p>\n Martha Mokaya, BSc, MBA- Data Manager</p>\n<p>\n Wilson Lokitala Ekiru, BSc IT- Assistant Data Manager</p>\n<p>\n Agnes M. Nzioka, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Betty Meli, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Michael Tanui, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Julie Choge - Recruitment Officer</p>\n<p>\n Amina Msuo Shali- Recruitment Officer</p>\n<p>\n Dorothy Mwimali - Recruitment Officer</p>\n<p>\n Cecilia Chebet, Dip Counselling - Recruitment Officer</p>\n<p>\n Beatrice Jakait, B Pharm- Back-up Pharmacist</p>\n<p>\n Zipporah Sambili, Dip Pharm- Back-up Pharmaceutical Technologist</p>\n<p>\n Chris Sande, KHRCN- Study Nurse</p>\n
      • other_details_explanation<p style=\"margin-left:36.0pt;\">\n The ultimate objective of this study is to determine whether an oral regimen (e.g., fluconazole alone) is acceptably potent and well tolerated for the treatment of HIV-associated CM.  A phase III clinical trial to compare the selected dose of fluconazole with a standard ampho B-based regimen would be of interest to providers where ampho B is available and should follow this study. In settings where use of an ampho B-based regimen is not feasible, fluconazole is often used at suboptimal doses. Establishing whether doses of fluconazole of 1200 mg or greater are tolerable and more effective than lower doses would be immediately applicable to patient care in these settings.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Moi University, Moi Teaching and Referral Hospital Institutional Research and Ethics committee. Granted continuing approval on 30th May 2013 for the Eldoret site.</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration48 weeks after enrolment of the last participant
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of care i.e. amp
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states7 (seven)
      • number_of_sites2
      • multi_country_listKenya, India, Thailand, South Africa, Peru, Zimbabwe, U.S.A
      • data_monitoring_committeeYes
      • total_enrolment_per_siteUnknown
      • total_participants_worldwide192
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameN/A
      • investigator1_middle_name
      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailamsiika@africaonline.co.ke
      • organisations_transferred_No
      • number_participants30 at Eldoret site
      • notification
      • approval_date11-05-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-06-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This study achieved its international accrual target of 168 participants at the end of 2016. Of these, 26 were from the MUCRC in Eldoret. Given the short 24 week follow up period, the last participant on study exited on January 31, 2017. Data analysis is currently ongoing and results will be sent to ECCT and disseminated to participants once they become available. All activities at the site for this study have been completed.</p>\n<p>\n  </p>\n
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-12-07 10:52:47
      • created2013-06-04 11:44:11
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id88
        • application_id143
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP O Box, 4606-30100, Eldoret
        • telephone0721280785
        • emailamsiika@africaonline.co.ke
        • created2013-06-04 12:34:53
        • modified2013-06-07 12:25:39
    • SiteDetail(array)
      • 0(array)
        • id110
        • application_id143
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressAMPATH at MTRH, Nandi Road, Eldoret
        • contact_detailsP O Box 4606 Eldoret
        • contact_personAllan Sudoi
        • site_capacity(null)
        • misc(null)
        • created2013-06-04 12:34:53
        • modified2013-06-07 12:25:39
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id69
        • application_id143
        • sponsorThe National Institute of Allergy and Infectious Diseases
        • sponsor_type(null)
        • contact_personUmesh G. Lalloo, MD, FRCP
        • addressNelson R. Mandela School of Medicine Private Bag 7 Congella Durban 4013
        • telephone_number27 31 260 4637
        • fax_number
        • cell_number27 31 260 4637
        • email_addresslalloo@nu.ac.za
        • created2013-06-04 12:34:53
        • modified2013-06-07 12:25:39
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • trial_human_pharmacology1
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php