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      • id569
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      • abstract_of_study<p>\n SYNOPSIS A Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo. The sponsor, in collaboration with Bavarian Nordic (BN) and Walter Reed Army Institute of Research (WRAIR), is investigating the potential of a prophylactic Ebola vaccine regimen comprised of the following 2 candidate Ebola vaccines: Ad26.ZEBOV is a monovalent vaccine expressing the full length Ebola virus (EBOV, formerly known as Zaire ebolavirus) Mayinga glycoprotein (GP), and is produced in the human cell line PER.C6®. MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN-Filo®, is a multivalent vaccine expressing the Sudan virus (SUDV) GP, the EBOV GP, the Marburg virus (MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein (NP), and is produced in chicken embryo fibroblast cells. The EBOV GP expressed by MVA-BN-Filo has 100% homology to the one expressed by Ad26.ZEBOV. Two populations will be studied in this protocol: healthy adults and human immunodeficiency virus (HIV)-infected adults, ages 18-70 years inclusive, will be enrolled. Ad26.ZEBOV and MVA-BN-Filo will be evaluated as a heterologous prime-boost regimen. The first schedule to be evaluated is prime vaccination with MVA-BN-Filo followed by a boost with Ad26.ZEBOV 14 days later. In the second schedule, Ad26.ZEBOV is used to prime a filovirus-specific immune response and MVA-BN-Filo is used to boost the immune response 28 days later. The EBOV GP that is currently circulating in West Africa has 97% homology to the EBOV GP used in this vaccine regimen. STUDY RATIONALE • Enlarge the safety and immunogenicity database for the Ad26.ZEBOV/MVA-BN-Filo 1, 29-day prime-boost regimen in healthy adults. • Assess the safety and immunogenicity of Ad26.ZEBOV/MVA-BN-Filo 1, 29-day prime-boost regimen in HIV-infected subjects and determine the effect of vaccination on HIV disease. • Enlarge the safety and immunogenicity database for MVA-BN-Filo/Ad26.ZEBOV 1, 15 day prime-boost regimen in healthy adults and HIV-infected adults.</p>\n<p>\n  </p>\n
      • study_title<p>\n A Randomized, Observer-blind, Placebo-controlled, Two part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo</p>\n
      • laymans_summary<p>\n Ebola virus disease is caused by an infection with a virus known as the Ebolavirus. The disease is characterized by symptoms such as fever, body aches, diarrhoea, bleeding, and vomiting. According to the World Health Organization, the number of people who die among the population having Ebola virus disease ranges from 25% to 90%. Vaccination is one of the most effective ways to prevent illness caused by viruses. A vaccine contains a non-functional part of the virus that is recognized by the body's protective immune system. The body then produces a response that prevents illness if the person is exposed to that virus again. This process is known as an immune response. The investigational treatment consists of a 2 dose vaccine regimen, 1 dose of Ad26.ZEBOV and 1 dose of MVA-BN-Filo vaccine, for the prevention of Ebola virus disease (Zaire ebolavirus species). This combination will be given at 2 different intervals between the 2 vaccine doses. The first schedule will include MVA-BN-Filo as the first dose followed by Ad26.ZEBOV as the second dose. The second schedule will include Ad26.ZEBOV as the first dose followed by MVA-BN-Filo as the second dose. In this study, researchers want to know the safety of the Ebola vaccine regimen in healthy adults and in human immunodeficiency virus (HIV*)-infected adults when administered using different vaccination schedules and interval. In addition, researchers want to understand the immune responses induced by the Ebola vaccine regimen by performing some tests. *HIV infection affects cells of the immune system and decreases their ability to fight infections. Participants can take part in this study if they have never received an Ebola vaccine, have not been diagnosed with Ebola virus disease, and have not travelled to any place where Ebola virus disease was confirmed up to 1 month before the study starts. Participants in the HIV-infected cohort should have a documented HIV infection within 6 months before the study start and be taking medicines for the treatment of HIV infection for the duration of the study. During the study, all participants will go through screening to confirm if they can take part in the study. Once enrolled, participants will be divided into 2 groups, healthy adults and participants with HIV infection between 18 to 70 years of age. All participants will receive either study vaccine (Ad26.ZEBOV, MVA-BN-Filo) or placebo, which does not contain the study vaccine, but looks like it. All vaccines will be given as an injection in the muscle. This study will be conducted in 2 parts: • • In Part 1 performed in the USA, participants will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15. • • In Part 2 performed in Africa, participants will be further divided into 2 groups. • o Participants in Group 1 will receive Ad26.ZEBOV or placebo on Day 1 followed by MVA-BN-Filo or placebo on Day 29. • o Participants in Group 2 will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15. During the study, participants will undergo different study assessments and tests. These include blood tests, vital signs (such as pulse, blood pressure, and temperature), electrocardiograms, physical exams, and pregnancy test for women. Any side effects reported by the participants will also be recorded throughout the study. Blood samples will be taken at several time points to understand how many participants responded to the vaccine regimen and to what extent. There will be a follow-up phase up to 1 year after the second dose to monitor the participants’ health and to collect blood samples for immune response assessments. The overall duration of the study will be approximately 3 years.</p>\n
      • short_titleRV456
      • protocol_noECCT/16/11/04
      • version_noAmendment 2
      • date_of_protocol08-03-2016
      • study_drugAd26.ZEBOV and MVA-BN-Filo
      • disease_conditionEBOLA
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
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      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmargaretodongo@usamru-k.org
      • applicant_covering_letter1
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      • applicant_registration_ctr(null)
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      • declaration_applicantSTACEY MAUREEN OKALLO GONDI
      • declaration_date114-11-2016
      • declaration_principal_investigatorDR JANET OYIEKO
      • declaration_date214-11-2016
      • placebo_presentYes
      • study_objectives<p>\n The purpose of this study is to assess the safety, tolerability and immunogenicity of different vaccination schedules of Ad26.ZEBOVand MVA-BN-Filo administered intramuscularly (IM) as 2-dose heterologous regimens in healthy and in HIV-infected adults.</p>\n
      • principal_inclusion_criteria<p>\n 4.1. Inclusion Criteria 4.1.1. Inclusion Criteria for Healthy Adult Subjects Each potential subject must satisfy all of the following criteria to be enrolled in the study. 1. Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. In case the subject cannot read or write, the procedures must be explained and informed consent must be witnessed by a literate third party not involved with the conduct of the study. 2. Subject must be a man or woman aged 18 to 70 years of age, inclusive at screening. 3. Subject must be healthy in the investigator’s clinical judgment on the basis of medical history, physical examination and vital signs performed at screening. 4. Subject must be healthy on the basis of clinical laboratory tests and ECG (only in subjects >50 years) performed at screening. If the results of the laboratory screening tests and ECG are outside the institutional normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator. However, the subject should not be included when hemoglobin is lower than the institutional normal reference range (or below the values in Attachment 3 when that range is not available). Note: The safety laboratory assessments at screening are to be performed within 28 days prior to the prime vaccination and may be repeated if they fall outside this time window. Note: In case of menstruation, urinalysis must be postponed but a result should be available before the prime vaccination. All urinalyses should be collected as freshly voided, mid-stream, clean catch samples obtained after proper cleansing. Note: If laboratory screening tests are out of range and deemed clinically significant, repeat of screening tests is permitted only once using an unscheduled visit during the screening period to assess eligibility. 5. Before randomization (on Day 1), a woman must be either: − Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies, beginning at least 28 days prior to vaccination until at least 3 months after the boost vaccination. The sponsor considers the following methods of birth control to be highly effective: established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods (condom or occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository); male partner sterilization (the vasectomized partner should be the sole partner for that subject). More restrictive measures may be required by the site. Note: Reliance on abstinence or natural family planning are not acceptable birth control methods for sexually active women of child-bearing potential. VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B]) Clinical Protocol VAC52150EBL2003 Amendment 2 49 Status: Approved, Date: 8 March 2016 OR − Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 2 years) or permanently sterilized (eg, bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy. Note: If the social situation of a woman changes after start of the study (eg, woman who is not heterosexually active becomes active), she must begin a highly effective method of birth control, as described above. 6. A woman of childbearing potential must have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test immediately prior to each study vaccine administration. Note: If the pregnancy test result is positive, in order to maintain subject confidentiality, the investigator will ensure adequate counseling and follow-up will be made available. 7. A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to prime vaccination until at least 3 months after the boost vaccination, unless a vasectomy was performed more than 1 year prior to screening. 8. Subject must be available and willing to participate for the duration of the study visits and follow-up. 9. Subject must be willing and able to comply with the protocol requirements, including the Prohibitions and Restrictions specified in Section 4.3. 10. Subject must be willing to provide verifiable identification. 11. Subject must have a means to be contacted. 12. Subject must pass the test of understanding (TOU) (passing score: ≥90%) (Attachment 1).</p>\n
      • principal_exclusion_criteria<p>\n 1. Has received any candidate Ebola vaccine. 2. Diagnosed with Ebola virus disease, or prior exposure to EBOV, including travel to epidemic Ebola areas less than 1 month prior to screening. Note: Participation of international volunteers to Ebola operations is allowed, but they should comply with the prohibitions and restrictions as specified in Section 4.3. 3. Has received any experimental candidate Ad26- or MVA-based vaccine in the past or received any other investigational drug or investigational vaccine or used an invasive investigational medical device within 3 months prior to screening. Note: Receipt of any approved vaccinia/smallpox vaccine or Ad-based candidate vaccine other than Ad26 at any time prior to study entry is allowed. 4. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines [eg, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-Filo vaccine]), including known allergy to egg, egg products and aminoglycosides. VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B]) Clinical Protocol VAC52150EBL2003 Amendment 2 51 Status: Approved, Date: 8 March 2016 5. Subject with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded from prime vaccination at that time, but may be rescheduled for prime vaccination at a later date. 6. HIV type 1 or type 2 infection. Note: If the HIV test result is positive, in order to maintain subject confidentiality, the investigator will ensure adequate counseling and follow-up will be made available. 7. A woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study or within at least 3 months after the boost vaccination. 8. Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, other systemic infections) or clinically significant findings during screening of medical history, ECG (only in subjects >50 years), physical examination, vital signs or laboratory testing for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments. Note: Subjects who have recently received treatment for acute, uncomplicated malaria are eligible for participation if at least 3 days have elapsed from the conclusion of a standard, recommended course of therapy for malaria; subjects who are acutely ill with malaria at the time of screening should complete therapy and wait an additional 3 days after completion before screening for the study. Note: Subjects with sickle cell trait can be included. 9. History of or underlying liver or renal insufficiency, or significant cardiac, vascular, pulmonary (eg, persistent asthma), gastrointestinal, endocrinic, neurologic, hematologic, rheumatologic, psychiatric or metabolic disturbances or eczema. 10. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered cured. Subjects with malignancies who are currently being treated or are not surgical cures are excluded. 11. Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening or planned major surgery through the course of the study (from screening until completion of the study, see Section 10.1). 12. Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive therapy. 13. Receipt of any disallowed therapies as noted in Section 8 before the planned administration of the prime vaccine on Day 1. 14. Is currently participating in or planning to participate in another clinical study during the study. Note: Participation in an observational clinical study is allowed. VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B]) Clinical Protocol VAC52150EBL2003 Amendment 2 52 Status: Approved, Date: 8 March 2016 15. Donation of a unit of blood within 8 weeks before Day 1 or plan to donate blood until 42-days post-boost. 16. Receipt of blood products or immunoglobulin within 3 months prior to screening and during participation in the study. 17. Current or past abuse of alcohol, recreational or narcotic drugs, which in the investigator’s opinion would compromise the subject’s safety and/or compliance with the study procedures. 18. History of chronic urticaria (recurrent hives). 19. Subject cannot communicate reliably with the investigator. 20. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study. 21. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.</p>\n
      • primary_end_points<p>\n Primary Endpoints The primary endpoints are: • Safety as determined by: − Adverse events, collected until the 42-day post-boost visit. − Serious adverse events, collected until the end of the study. − Solicited local and systemic adverse events (reactogenicity), collected until 7 days after each vaccination. • Magnitude, kinetics and durability of humoral immune response against the EBOV GP by determining binding antibody levels using ELISA (in ELISA units/mL and/or endpointtiters) until the 21-day post-boost visit.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • 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 The KEMRI/WRP Kombewa Clinical Research Center(KCRC) is designed for large clinical trials and has a full clinical laboratory including microbiology capability.Over the years the site has carried out vaccine, drug and epidemiologicalThe KCRC has been recognized (report of the George Institute, 2007) as one of the premier sites in Africa to conduct clinical trials.</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • 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_duration2 YEARS
      • 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
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKOMBEWA CLINICAL RESEARCH CENTRE
      • single_site_physical_addressOFF KISUMU BONDO ROAD, OPPOSITE KOMBEWA SUB COUNTY HOSPITAL
      • single_site_contact_personDR JANET OYIEKO
      • single_site_telephoneTEL +25471996988
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesNumber countries 6
      • number_of_sites
      • multi_country_listKenya, Uganda, Tanzania, Mozambique, Nigeria, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKombewa Site 50
      • total_participants_worldwide575
      • 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_elderlyYes
      • 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
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      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJANET
      • investigator1_middle_name
      • investigator1_family_nameOYIEKO
      • investigator1_qualificationMD, MMed (Paeds)
      • investigator1_professional_addressP.O BOX 54
      • investigator1_telephone+254721996988
      • investigator1_emailjanet.oyieko@usamru-k.org
      • organisations_transferred_No
      • number_participantsKombewa Site 50
      • notification
      • approval_date28-01-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted23-04-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div>\n This study was conducted in the USA (Part 1) and Africa (Part 2) and evaluated the safety, tolerability and immunogenicity of 2-dose heterologous vaccination regimens using Ad26.ZEBOV (5×1010 vp) and MVABN-Filo (1×108 Inf.U) in HIV-uninfected and HIV-infected adult participants. One regimen consisted of Ad26.ZEBOV on Day 1 (dose 1) followed by MVA-BN-Filo (dose 2) 28 days later (Part 2, Group 1), and one regimen consisted of MVA-BN-Filo on Day 1 (dose 1) followed by Ad26.ZEBOV (dose 2) 14 days later (Part 1 and Part 2, Group 2). Both regimens evaluated in this study were well-tolerated and no safety concerns were identified. Overall, adverse events reported post vaccination were mild in the majority of participants and transient in nature. No deaths or serious adverse events considered to be related to study vaccine were reported. There were no immediate reportable events, and only 1 participant did not receive dose 2 due to an adverse event of transient grade 1 leukocytosis considered possibly related to study vaccine by the investigator. Both regimens used in this study induced binding antibody responses (FANG ELISA) at 21 days post</div>\n<div>\n dose 2 in almost all (96% to 99%) participants in Part 1 and Part 2. Pooled FANG ELISA data for theMVA-BN-Filo, Ad26.ZEBOV 14-day interval schedule in Part 1 and Part 2 were generally similar to those from either study part alone. At 21 days post dose 2, the GMC in HIV-uninfected participants was higher than the GMC in HIV-infected participants. In both groups (HIV-uninfected and HIV-infected), responses were observed until the last assessment 1 year post dose 2, when a difference between the GMCin HIV-uninfected vs. HIV-infected participants was still present for the MVA-BN-Filo, Ad26.ZEBOV</div>\n<div>\n regimen. At 21 days post dose 2 in Part 1, EBOV GP-specific CD4+ T-cell responses were observed in 52% of HIV-uninfected and 39% of HIV-infected participants. EBOV GP-specific CD8+ T-cell responses were observed at this timepoint in 30% of HIV-uninfected and 22% of HIV-infected participants.</div>\n
      • implication_results<div>\n In summary, this is the first study to demonstrate safety and EBOV GP-specific immunogenicity in PLWH with an Ebola vaccination regimen of MVA-BN-Filo followed by</div>\n<div>\n Ad26.ZEBOV 14 days later. These results show that an accelerated vaccination schedule is well tolerated in both PWOH and PLWHand induces a broad array of durable humoral and cellular immune responses. These findings support continued consideration for accelerated regimen development for rapid deployment among outbreak responders and relevant global populations at immediate risk.</div>\n
      • quantity_imported210
      • quantity_dispensed153
      • quantity_destroyed57
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2025-02-17 16:23:33
      • created2016-11-14 11:11:48
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id368
        • application_id569
        • given_nameJANET
        • middle_name
        • family_nameOYIEKO
        • qualificationMD, MMed (Paeds)
        • professional_addressP.O BOX 54
        • telephone+254721996988
        • emailjanet.oyieko@usamru-k.org
        • created2016-11-14 11:31:40
        • modified2020-04-23 12:12:13
    • SiteDetail(array)
      • 0(array)
        • id449
        • application_id569
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-11-14 11:31:40
        • modified2020-04-23 12:12:13
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id294
        • application_id569
        • sponsorCrucell Holland B.V.
        • sponsor_typeIndustry
        • contact_personCynthia B. Robinson, MD
        • addressP.O. Box 2048 2301 CA Leiden The Netherlands
        • telephone_number +1 215 793-7681
        • fax_number +1 215 986-1027
        • cell_number +1 215 793-7681
        • email_addressCRobins6@its.jnj.com
        • created2016-11-14 11:31:40
        • modified2020-04-23 12:12:13
  • 1(array)
    • Application(array)
      • id568
      • user_id613
      • trial_status_id5
      • abstract_of_study<p>\n The abstract/synopsis of this protocol is detailed on Page 15 of the protocol attached.</p>\n
      • study_title<p>\n A randomized, obsever-blind, placebo controlled, two-part, Phase 2 study to evaluate the Safety, Tolerability and Immunogenicity of Two prime-boost regimen of the candidate Prophylactic vaccines for Ebola Ad26-ZEBOV and MVA-BN Filo.</p>\n
      • laymans_summary<div>\n The sponsor, in collaboration with Bavarian Nordic GmbH (BN) and Walter Reed Army Institute of Research (WRAIR), is investigating the potential of a prophylactic Ebola vaccine regimen comprised of the following 2 candidate Ebola vaccines: Ad26.ZEBOV is a monovalent vaccine expressing the full length Ebola virus (EBOV, formerly known as Zaire ebolavirus) Mayinga glycoprotein (GP), and is produced in the human cell line PER.C6®. MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN-Filo®, is a multivalent vaccine expressing the Sudan virus (SUDV) GP, the EBOV GP, the Marburg virus (MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein (NP), and is produced in chicken embryo fibroblast cells. The EBOV GP expressed by MVA-BN-Filo has 100%</div>\n<div>\n homology to the one expressed by Ad26.ZEBOV.</div>\n<div>\n Two populations will be studied in this protocol: healthy adults and human immunodeficiency virus (HIV)-infected adults, ages 18-70 years inclusive, will be enrolled.</div>\n
      • short_titleRV 456: Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo
      • protocol_noECCT/16/11/05
      • version_noApproved version dated 08 March 2016
      • date_of_protocol08-03-2016
      • study_drugEbola Ad26.ZEBOV and MVA-BN-Filo vaccines
      • disease_conditionEbola
      • 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
      • comparatorYes
      • comparator_nameNormal Saline Placebo
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosphat.kosgei@usamru-k.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_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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Josphat Kosgei
      • declaration_date114-11-2016
      • declaration_principal_investigatorDr Fredrick Sawe
      • declaration_date214-11-2016
      • placebo_presentYes
      • study_objectives<div>\n Primary Objectives</div>\n<div>\n • To assess the safety and tolerability of different vaccination schedules of Ad26.ZEBOV and</div>\n<div>\n MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost regimens in healthy</div>\n<div>\n adults and in HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination</div>\n<div>\n on Days 1 and 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on</div>\n<div>\n Days 1 and 15, respectively.</div>\n<div>\n • To assess the immune responses to the EBOV GP (as measured by [enzyme-linked immunosorbent</div>\n<div>\n assay] ELISA antibody concentration) of different vaccination schedules of Ad26.ZEBOV and</div>\n<div>\n MVA-BN-Filo administered IM as heterologous prime-boost regimens in healthy adults and in</div>\n<div>\n HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on Days 1 and</div>\n<div>\n 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on Days 1 and 15,</div>\n<div>\n respectively.</div>\n
      • principal_inclusion_criteria<p>\n Healthy adults, both HIV negative and positive, aged 18 to 70 years.</p>\n
      • principal_exclusion_criteria<p>\n Recepient of Ebola vaccine previosly.</p>\n<p>\n Has been diagnosed with Ebola virus infection.</p>\n
      • primary_end_points<p>\n Safety, as assessed by adverse events.</p>\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_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • 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 The site has the capacity to conduct the study, in terms of human resources, infrastructure, experience, emergency facilities. This is well detailed in the Site Specific Addendum attached.</p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None.</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU approved on October 17 2016.</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable.</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable.</p>\n
      • estimated_duration64 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
      • 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_states6
      • number_of_sites2
      • multi_country_listUSA, Kenya, Nigeria, Uganda, Tanzania, Mozambique
      • data_monitoring_committeeYes
      • total_enrolment_per_site100 in Kericho and 50 in Kombewa, Kisumu
      • total_participants_worldwide575
      • 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_elderlyYes
      • 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_nameElizabeth
      • investigator1_middle_nameChebet
      • investigator1_family_nameNgetich
      • investigator1_qualificationBSc (Nursing), CRA
      • investigator1_professional_addressKEMRI/WRP Kericho
      • investigator1_telephone+254 713 603 217
      • investigator1_emailelizabeth.ngetich@usamru-k.org
      • organisations_transferred_Yes
      • number_participants150
      • notification
      • approval_date02-03-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This study was a  Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Fil. The primary objectives of this study were to  assess the safety and tolerability of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost regimens in healthy adults and in HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on Days 1 and 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on Days 1 and 15, respectively.</p>\n<p>\n People without HIV (PWOH) and people living with HIV (PLWH) aged 18-70 years were enrolled at six sites in five African countries: Kenya, Mozambique, Nigeria, Tanzania, and Uganda. A CD4+ cell count >200 cells/μL at screening was an eligibility requirement for PLWH, and those with a screening CD4+ cell count >200 to <350 cells/μL must have been on stable antiretroviral therapy (ART; no regimen change in the four weeks preceding screening). All participants provided written informed consent. The RV 456b study enrolled healthy subjects and HIV-infected subjects, both male and female (aged 18 to 70 years inclusive). There are no changes from the anticipated population.</p>\n<p>\n No study-related SAE was reported for the RV 456b during the study. The majority of solicited AEs across all sites were of mild-to-moderate severity in the 14- and 28-day interval groups. Additionally, most solicited AEs were ≤3 days in duration (61% and 91% of solicited local AEs in the vaccine and placebo groups, respectively, and 53% and 50% of solicited systemic AEs, respectively). The most frequent (occurring in >20% of participants) solicited local AEs were injection-site pain and injection-site pruritus, while the most frequent (occurring in >40% of participants) solicited systemic AEs were fatigue, headache, and myalgia. All SAEs were considered unrelated to the study vaccine. No deaths were reported.</p>\n<p>\n  </p>\n
      • implication_results<p>\n This is the first study to demonstrate safety and EBOV GP-specific immunogenicity in PLWH with an Ebola vaccination regimen of MVA-BN-Filo followed by Ad26.ZEBOV 14 days later. These results show that an accelerated vaccination schedule is well tolerated in both PWOH and PLWH and induces a broad array of durable humoral and cellular immune responses. These findings support continued consideration for accelerated regimen development for rapid deployment among outbreak responders and relevant global populations at immediate risk.</p>\n<p>\n The following publications resulted from this study:</p>\n<ul>\n <li>\n Ake, J.A.; Paolino, K.; Hutter, J.N.; Cicatelli, S.B.; Eller, L.A.; Eller, M.A.; Costanzo, M.C.; Paquin-Proulx, D.; Robb, M.L.; Tran, C.L.; et al. <em><strong>Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Tria</strong></em>l. Vaccines 2024, 12, 497. https://doi.org/10.3390/vaccines12050497</li>\n <li>\n Betty Mwesigwa, Fredrick Sawe, Janet Oyieko, Joel Mwakisisile, Edna Viegas, Gideon Akindiran Akintunde, Josphat Kosgei, Afoke Kokogho, Nyanda Ntinginya, Ilesh Jani, Georgi Shukarev, Jay W Hooper, Steven A Kwilas, Lucy A Ward, Janice Rusnak, Callie Bounds, Rachel Overman, Christopher S Badorrek, Leigh Anne Eller, Michael A Eller, Christina S Polyak, Amber Moodley, Chi L Tran, Margaret C Costanzo, David J Leggat, Dominic Paquin-Proulx, Prossy Naluyima, Dickson Nkafu Anumendem, Auguste Gaddah, Kerstin Luhn, Jenny Hendriks, Chelsea McLean, Macaya Douoguih, Hannah Kibuuka, Merlin L Robb, Cynthia Robinson, Julie A Ake, <em><strong>Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa</strong></em>, Clinical Infectious Diseases, 2024;, ciae215, https://doi.org/10.1093/cid/ciae215</li>\n</ul>\n<p>\n  </p>\n<p>\n  </p>\n
      • quantity_importedFind attached RV 456 Study Product Recovery Reports
      • quantity_dispensedFind attached RV 456 Study Product Recovery Reports
      • quantity_destroyedFind attached RV 456 Study Product Recovery Reports
      • quantity_exportedFind attached RV 456 Study Product Recovery Reports
      • balance_siteFind attached RV 456 Study Product Recovery Reports
      • final_date0000-00-00
      • modified2024-10-17 16:17:40
      • created2016-11-14 06:53:35
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id367
        • application_id568
        • given_nameFredrick
        • middle_nameKipyego
        • family_nameSawe
        • qualificationMBChB, MMED
        • professional_addressKEMRI/WRP Kericho
        • telephone+254 703 247 902
        • emailfredrick.sawe@usamru-k.org
        • created2016-11-14 07:06:27
        • modified2020-03-18 07:52:01
    • SiteDetail(array)
      • 0(array)
        • id447
        • application_id568
        • county_id35
        • site_nameKEMRI/WRP Kericho
        • physical_addressKericho
        • contact_detailsP.O. Box 1357-20200
        • contact_personDr Fredrick Sawe
        • site_capacity(null)
        • misc(null)
        • created2016-11-14 07:06:27
        • modified2020-03-18 07:52:01
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 1(array)
        • id448
        • application_id568
        • county_id42
        • site_nameKEMRI/WRP Kombewa, Kisumu
        • physical_addressKombewa
        • contact_details+254 721 996 988
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2016-11-14 07:44:29
        • modified2020-03-18 07:52:01
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id293
        • application_id568
        • sponsorCrucell Holland B.V., a Janssen pharmaceutical company of Johnson & Johnson
        • sponsor_typeIndustry
        • contact_person
        • addressArchimedesweg 4, 2333 CN Leiden, Netherlands
        • telephone_number+31715199100
        • fax_number
        • cell_number+31715199100
        • email_addressJanssenIDVNL@its.jnj.com
        • created2016-11-14 07:06:27
        • modified2020-03-18 07:52:01
  • 2(array)
    • Application(array)
      • id682
      • user_id85
      • trial_status_id(null)
      • abstract_of_study<div>\n SYNOPSIS</div>\n<div>\n Protocol title:<span style=\"white-space:pre\"> </span>A Randomized, Open label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel (OZ439) given in combination with Ferroquine (FQ) and FQ alone, in African Patients with Uncomplicated Plasmodium falciparum Malaria</div>\n<div>\n Short title:<span style=\"white-space:pre\"> </span>A Randomized, Open, Parallel-group, Single Dose, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel in combination with Ferroquine (FQ) and FQ alone, in African Patients with Uncomplicated Plasmodium falciparum Malaria</div>\n<div>\n Rationale:</div>\n<div>\n Plasmodium falciparum (P. falciparum) malaria remains a deadly endemic parasitic disease, with 212 million new cases and over 429,000 deaths reported in 2015. World Health Organization (WHO) guidelines recommend that artemisinin-based combination therapies (ACT) are used to treat uncomplicated P. falciparum malaria, which is administrated in a 3-day regimen. Sanofi and Medicines for Malaria Venture (MMV) are co-developing a fixed dose combination (FDC) of FQ and artefenomel (OZ439) for a single dose treatment of uncomplicated malaria in adults and children. Per Food and Drug Administration (FDA) guidance for co-development of 2 new investigational drugs for use in combination, it is recommended to demonstrate the contribution of each individual component to the effect of the combination. This phase 2a study will test clinical and parasiticidal activity, pharmacokinetics (PK) and safety of 3 doses of OZ439 associated with a fixed dose of FQ and FQ alone.</div>\n<div>\n  </div>\n
      • study_title<p>\n A Randomized, Open label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel (OZ439) given in combination with Ferroquine (FQ) and FQ alone, in African Patients with Uncomplicated Plasmodium falciparum Malaria</p>\n
      • laymans_summary<p>\n The WHO recommends a 3-day regimen of drugs called artemisinin-based combination therapy (ACT) to treat uncomplicated malaria caused by the <em>P. falciparum</em> malaria parasite (1). However, some patients, particularly children, may not take the treatment on all 3 days (2). A single dose could be a better treatment since only one dose is required.</p>\n<p>\n  </p>\n<p>\n This clinical study was carried out in 5 sub-Saharan African countries. Recruited patients were randomly (treatment allocated by chance, similar to flipping a coin) given one of 4 treatments: 400 mg ferroquine (FQ) alone or in combination with another drug, artefenomel, at doses of 300, 600 or 1000 mg. Patients were between 14 and 69 years of age with uncomplicated <em>P. falciparum</em> malaria and parasite numbers between 3,000 and 50,000 per μL of blood.</p>\n<p>\n The primary objective of the study was to see if a relationship could be detected between the amount of artefenomel in the blood following administration of the different doses of artefenomel (in combination with FQ), or FQ administered alone, and the number of patients who were cured or not cured of their original infection, as measured by the absence or presence of parasites in the blood 28 days after treatment.</p>\n<p>\n 140 patients entered the study and were given treatment.</p>\n<p>\n FQ alone, and in combination with artefenomel was well tolerated with safety findings aligned with what was known about the drugs from previous studies. Seven patients had an increase in some biological measurements which could reflect a muscle problem, although no symptoms of actual muscle problems such as weakness, tenderness or pain were seen. There was no clinically relevant effect of the drug treatments on the function of the heart.</p>\n<p>\n 1. World Health Organization (WHO). Guidelines for the treatment of Malaria. Third edition. 2015. ISBN: 978 92 4 154912 7.</p>\n<p>\n 2. World Health Organization (WHO). Management of severe malaria: a practical handbook. Third edition. 2012. ISBN: 978924154852 6.</p>\n
      • short_titleA Randomized, Open, Parallel-group, Single Dose, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel in combination with Ferroquine (FQ) and FQ alone, in African Patients with Unc
      • protocol_noECCT/18/07/07
      • version_no3
      • date_of_protocol13-11-2017
      • study_drugOZ439 (artefenomel) and SSR97193 (ferroquine)
      • disease_conditionUncomplicated Plasmodium falciparum Malaria
      • 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_nameOZ439 (artefenomel) and SSR97193 (ferroquine)
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressezekiel.muinde@yahoo.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_countries1
      • applicant_addendum1
      • 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_applicantEZEKIEL MUINDE
      • declaration_date106-08-2018
      • declaration_principal_investigatorDr Grace K. Kaguthi
      • declaration_date206-08-2018
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n List them here: in Appe</div>\n<div>\n Age</div>\n<div>\n I 01. Participants must be 14 to 69 years of age inclusive, at the time of signing the informed consent.</div>\n<div>\n  </div>\n<div>\n Type of participant and disease characteristics</div>\n<div>\n I 02. Participants who present with uncomplicated P. falciparum malaria, with a fever as defined with axillary temperature ≥37.5 degress Celsius (°C) or oral/rectal/tympanic temperature ≥38°C or history of fever in the previous 24 hours (history of fever must be documented), with a mono-infection with P.falciparum and parasitemia (microscopically, blood smear) ≥3,000 and ≤50,000 asexual parasites/µL of blood.</div>\n<div>\n  </div>\n<div>\n Weight</div>\n<div>\n I 03. Body weight within 35 and 90 kg (inclusive).</div>\n<div>\n  </div>\n<div>\n Sex</div>\n<div>\n I 04. Male and Female</div>\n<div>\n         a) Male participants: A male participant must agree to use contraception as detailed in  </div>\n<div>\n             Appendix 5 of the Clinical Trial Protocol version 1 dated 13 November 2017 (CTP) for</div>\n<div>\n            3 months after the last dose of study treatment and refrain from donating sperm during</div>\n<div>\n            this period.</div>\n<div>\n          b) Female participants: A female participant is eligible to participate if she is not pregnant</div>\n<div>\n              (see Appendix 5 of the CTP), not breastfeeding, and at least one of the following</div>\n<div>\n              conditions applies:</div>\n<div>\n -<span style=\"white-space:pre\"> </span>Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of the CTP</div>\n<div>\n OR</div>\n<div>\n -<span style=\"white-space:pre\"> </span>A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 of the CTP for  3 months after the last dose of study treatment.</div>\n<div>\n  </div>\n<div>\n Informed Consent</div>\n<div>\n I 05. Capable of giving signed informed consent (if the patient is ≥age defining majority) as </div>\n<div>\n         Described in Appendix 3 of the CTP, which includes compliance with the requirements</div>\n<div>\n         and restrictions listed in the informed consent form (ICF) and in this protocol. Informed </div>\n<div>\n         consent signed by the legally acceptable representative (LAR) of the minor patient (<18    </div>\n<div>\n          years of age or <other .=\"\" accordance=\"\" age=\"\" defining=\"\" div=\"\" in=\"\" local=\"\" locally=\"\" with=\"\">\n <div>\n         regulation, minor participants with capacity for writing could sign off on an Assent Form. </div>\n <div>\n         For those who are able to understand but with no capacity for writing the Assent Form</div>\n <div>\n         would be read. In that case, an impartial witness could certify the document was read to</div>\n <div>\n         the child.</div>\n <div>\n  </div>\n </other></div>\n
      • principal_exclusion_criteria<p style=\"margin-left:6.3pt;\">\n <strong>Medical conditions</strong></p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 01.</strong> Presence of severe malaria.</p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 02. </strong>Known history or evidence of clinically significant gastrointestinal, cardiovascular,</p>\n<p style=\"margin-left:6.3pt;\">\n           hepatic, renal, hematological, respiratory, endocrine, immunological, infectious,</p>\n<p style=\"margin-left:6.3pt;\">\n           neurological (in particular convulsions), malignancy, psychiatric disease or symptoms</p>\n<p style=\"margin-left:6.3pt;\">\n           which, in the judgement of the investigator, might confuse the interpretation of the</p>\n<p style=\"margin-left:6.3pt;\">\n          safety information.</p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 03.</strong> Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in the</p>\n<p style=\"margin-left:6.3pt;\">\n           study or inability to tolerate oral treatment or severe diarrhea defined as 3 or more</p>\n<p style=\"margin-left:6.3pt;\">\n           watery stools per day.</p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 04.</strong> Severe malnutrition defined as a body mass index of less than 16 kg/m² for adults and</p>\n<p style=\"margin-left:6.3pt;\">\n           for children Z-score <-3 or weight for age (%) of the median <60.</p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 05.</strong> Splenectomized participants or presence of surgical scar on left hypochondrium.</p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 06. </strong>Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other</p>\n<p style=\"margin-left:6.3pt;\">\n          amino quinolones or to OZ439 or OZ277 or any of the excipients.</p>\n<p style=\"margin-left:6.3pt;\">\n  </p>\n<p style=\"margin-left:6.3pt;\">\n <strong>Prior/concomitant therapy</strong></p>\n<p style=\"margin-left:6.3pt;\">\n <strong>E 07. </strong>Participant treated with anti-malarial treatment:</p>\n<ul>\n <li>\n With PQP-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine within the previous 6 weeks.</li>\n <li>\n With amodiaquine or choroquine within the previous 4 weeks.</li>\n <li>\n With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.</li>\n <li>\n With any herbal products or traditional medicines, within the past 7 days.</li>\n</ul>\n<p>\n <strong>E 08. </strong>Previous treatment within 5 times the half-life or within the last 14 days, whichever the</p>\n<p>\n          Longest, which are: strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but</p>\n<p>\n          Inhibiting both CYP2C and CYP3A and/or CYP inducers (see <em>Appendix 6 of the CTP)</em>.</p>\n<p>\n <strong>E 09. </strong>Any treatment known to induce a prolongation of QT interval (see <em>Appendix 6 of the CTP</em></p>\n<p>\n  </p>\n<p>\n <strong>Prior/concurrent clinical study experience</strong></p>\n<p style=\"margin-left:34.6pt;\">\n <strong>E 10. </strong>Participated in any trial investigating OZ439 and/or FQ compounds.</p>\n<p style=\"margin-left:34.6pt;\">\n <strong>E 11. </strong>Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance</p>\n<p>\n <strong>E 12. </strong>Enrolled in another clinical trial within the past 4 weeks or during the study period</p>\n<p>\n  </p>\n<p>\n <strong>Diagnostic assessments</strong></p>\n<p style=\"margin-left:34.6pt;\">\n <strong>E 13. </strong>Mixed <em>Plasmodium</em> infection.</p>\n<p style=\"margin-left:34.6pt;\">\n <strong>E 14.</strong> Presence of Hepatitis A – immunoglobulin M (HAV-IgM), Hepatitis B surface antigen (HBs Ag) or Hepatitis C virus antibody (HCV Ab) and/or known to have active Hepatitis C virus RNA (HCV RNA)</p>\n<p style=\"margin-left:34.6pt;\">\n <strong>E 15.</strong> Laboratory parameters with abnormalities deemed clinically significant by the investigator.</p>\n<p>\n <strong>E 16.</strong> Abnormal LFT: aspartate transferase (AST) >2 upper limit of normal range (ULN), or alanine transferase (ALT) >2 ULN or total bilirubin >1.5 ULN</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:677px;height:314px;\">\n <p style=\"margin-left:34.6pt;\">\n <strong>E 17.  </strong>Positive pregnancy test at study screening for female participants of childbearing potential</p>\n <p style=\"margin-left:34.6pt;\">\n <strong>E 18.  </strong>QTcF >450 ms at screening or pre-dose</p>\n <p style=\"margin-left:34.6pt;\">\n <strong>E 19.  </strong>Hypokalemia (<3.5 mmol/L), hypocalcemia (<2.0 mmol/L) or hypomagnesemia (<0.5 mmol/L) at screening or pre-dose</p>\n <p style=\"margin-left:34.6pt;\">\n  </p>\n <p style=\"margin-left:34.6pt;\">\n <strong>Other exclusions</strong></p>\n <p>\n <strong>E 20. </strong>Any country-related specific regulation that would prevent the subject from entering the study - see <em>Appendix 9 of the CTP </em>(country specific requirements)</p>\n <p>\n <strong>E 21. </strong>Family history of sudden death or of congenital prolongation of the QT interval or known congenital prolongation of the QT-interval or any clinical condition known to prolong the QT interval e.g., participants with a history of symptomatic cardiac arrhythmias including atrial fibrillation (AF) or with clinically relevant bradycardia</p>\n <p>\n <strong>E 22.  </strong>Patient not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures or unable to drink</p>\n <p style=\"margin-left:34.6pt;\">\n  </p>\n <p style=\"margin-left:3.0pt;\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:677px;height:242px;\">\n <p style=\"margin-left:6.3pt;\">\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • primary_end_points<p style=\"margin-left:6.3pt;\">\n <strong>12.0 PRIMARY END POINT(S) :</strong></p>\n<p style=\"margin-left:6.3pt;\">\n  </p>\n<p style=\"margin-left:6.3pt;\">\n <strong>List them here:</strong></p>\n<p style=\"margin-left:6.3pt;\">\n  </p>\n<p style=\"margin-left:6.3pt;\">\n <strong>Primary Objective:</strong></p>\n<p style=\"margin-left:6.3pt;\">\n To show the contribution of OZ439 to the clinical and parasiticidal effect of OZ439/FQ combination by analyzing exposure-response of OZ439 measured by Day 28 PCR-corrected ACPR for the effect and the AUC of OZ439 as PK predictor.</p>\n<p style=\"margin-left:6.3pt;\">\n  </p>\n<p style=\"margin-left:6.3pt;\">\n <strong>Primary Endpoint:</strong></p>\n<p>\n Day 28 PCR-corrected ACPR (see <em>Section 10.3.1.1 of the CTP</em> for details</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic1
      • scope_pharmacogenomic1
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • 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 CLINICIANS-3</p>\n<p>\n LAB TECHNOLOGISTS-3</p>\n<p>\n PHARMACIST/PHARM TECH-3</p>\n<p>\n NURSES-5</p>\n<p>\n FIELD WORKERS-3</p>\n<p>\n COORDINATORS-2</p>\n<p>\n SET UP IN A FULL HOSPITAL FACILITY-SIAYA DISTRICT HOSPITAL/ KEMRI KISUMU</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Europe is a non-endemic Malaria zone. There are only imported malaria cases in <strong>Europe</strong>. In <strong>France, 3,560 imported cases were reported in 2011</strong>.</p>\n<p>\n Source: <a href=\"https://www.pasteur.fr/en/medical-center/disease-sheets/malaria\">https://www.pasteur.fr/en/medical-center/disease-sheets/malaria</a></p>\n<p>\n  </p>\n<p>\n Malaria, which was eliminated first from Metropolitan France (mainland and Corsica), then in the French West Indies and the Reunion Island during the 20^th century. <a href=\"https://www.sciencedirect.com/science/article/pii/S0399077X11000576?via%3Dihub\">https://www.sciencedirect.com/science/article/pii/S0399077X11000576?via%3Dihub</a></p>\n<p>\n  </p>\n<p>\n More information:</p>\n<p>\n Per WHO data, France is a non-endemic malaria zone.</p>\n<p>\n WHO report (2016): <a href=\"http://apps.who.int/iris/bitstream/10665/254913/1/WHO-HTM-GMP-2017.4-fre.pdf?ua=1\">http://apps.who.int/iris/bitstream/10665/254913/1/WHO-HTM-GMP-2017.4-fre.pdf?ua=1</a></p>\n<p>\n Additional WHO sources:</p>\n<p>\n <a href=\"http://www.who.int/gho/malaria/malaria_003.jpg?ua=1\">http://www.who.int/gho/malaria/malaria_003.jpg?ua=1</a> (image attached)</p>\n<p>\n <a href=\"http://gamapserver.who.int/gho/interactive_charts/malaria/cases/atlas.html\">http://gamapserver.who.int/gho/interactive_charts/malaria/cases/atlas.html</a> :</p>\n
      • other_details_regulatory_notapproved<div>\n Benin submitted 15 February 2018, outcome pending.</div>\n<div>\n Burkino-Faso – Submission date to be confirmed</div>\n<div>\n Uganda submitted 04 December 2017, outcome pending</div>\n<div>\n  </div>\n
      • other_details_regulatory_approved<p>\n Gabon submitted 02 March 2017, approved 02 April 2017      </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationStudy will last for up to 32 days for each participant: • Up to 1 day screening period before the single-dose treatment • 5 days of post-treatment surveillance, including 2 to 4 days hospitalization • 24±2 days follow-up
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNONE
      • 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_states5
      • number_of_sites2
      • multi_country_listBenin, Burkina-Faso, Gabon, Uganda and Kenya.
      • data_monitoring_committeeNo
      • total_enrolment_per_siteTotal enrolment in each Kenyan site: (if competitive enrolment, state minimum and maximum number per site.) 14 per site. Recruitment is competitive world-wide and there is no minimum or maximum number set per site. However, prior approval from the Sponsor is required before a site could recruit more participants above the estimated 14.\n\n
      • total_participants_worldwide140
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • 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_nameVIDELIS
      • investigator1_middle_nameNDUBA
      • investigator1_family_nameNZIOKA
      • investigator1_qualificationMBchB
      • investigator1_professional_addressKEMRI
      • investigator1_telephone0724522474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants28
      • notification<p>\n We paid for an expedited review.</p>\n
      • approval_date04-10-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted10-08-2018
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n The WHO recommends a 3-day regimen with artemisinin-based combination therapy (ACT) to treat uncomplicated <em>P. falciparum</em> malaria (1), however compliance is not optimal, particularly in children (2). A single dose treatment could offer the potential for optimal adherence.</p>\n<p>\n This was a randomized open label, parallel-group Phase 2a study in 5 sub-Saharan African countries. Single dose regimens of 3 dose levels of artefenomel (300, 600 and 1000 mg) in combination with 400 mg ferroquine (FQ), and 400mg FQ alone were administered to patients ≥ 14 to ≤69 years of age with uncomplicated <em>P. falciparum</em> malaria (≥3,000 to ≤50,000 asexual parasites/μL of blood by microscopy).</p>\n<p>\n The primary objective was to show the contribution of artefenomel to the adequate clinical and parasiticidal response (ACPR) of artefenomel/FQ combination by analyzing exposure-response of artefenomel on Day 28 polymerase chain reaction (PCR)-corrected ACPR by logistic regression analysis, using the area under the concentration curve (AUC(0-∞)) of artefenomel as the pharmacokinetic (PK) predictor. Key secondary objectives included evaluation of the exposure-response on crude Day 28 ACPR and evaluation of the safety and tolerability.</p>\n<p>\n 140 patients were randomized. The full PKPD efficacy population consisted of 132 patients and 121 patients were analyzed for PCR-corrected ACPR28 (cases of reinfection were considered excluded).</p>\n<p>\n The contribution of artefenomel exposure (AUC(0-∞)) to PCR-corrected ACPR28 could not be demonstrated for the artefenomel/FQ combination. After including FQ exposure (AUC(0-day28)), baseline parasitemia and study center as covariates in the model, no statistically significant relationship between artefenomel exposure and PCR-corrected ACPR was established (odds ratio 1.1; <em>p</em> 0.245). Similarly, the contribution of artefenomel exposure to crude ACPR28, could not be demonstrated. Even though 3 dose levels of artefenomel and FQ alone was studied and graphical explorations suggested a relationship between artefenomel concentration and efficacy, the study was probably under-powered to identify this effect. This may be due to the observed efficacy response for FQ alone being larger than that predicted in the clinical trial simulations, resulting in a smaller window to observe the artefenomel contribution. PCR-corrected ACPR28 was 80.8% (95% CI: 62.1-91.5%) for FQ alone and 90.3% (75.1-96.7%), 90.9% (76.4-96.9%) and 87.1% (71.1-94.9%) for FQ plus 300mg, 600 mg and 1000 mg of artefenomel respectively.</p>\n<p>\n FQ alone and in combination with artefenomel was overall well tolerated with safety findings aligned with previous findings. No new safety signals were identified.  7 patients presented with isolated clinically relevant creatinine phosphokinase increases (all less than 10 xULN with no clinical consequences). The concentration/ ECG analysis indicated a non-clinically significant artefenomel concentration-dependent QTcB prolongation. There was no effect of FQ on QTcB.</p>\n<p>\n 1. World Health Organization (WHO). Guidelines for the treatment of Malaria. Third edition. 2015. ISBN: 978 92 4 154912 7.</p>\n<p>\n 2. World Health Organization (WHO). Management of severe malaria: a practical handbook. Third edition. 2012. ISBN: 978924154852 6.</p>\n<p>\n  </p>\n
      • implication_results<p>\n The results of Study ACT14655 do not have any direct implications for current clinical practice. The study was not designed to achieve optimal efficacy, and as such this study may be viewed as a pharmacodynamic rather than an efficacy study.</p>\n<p>\n The study was designed to maximize the likelihood of achieving the primary objective of the study which was to evaluate the contribution of artefenomel to the overall clinical and parasiticidal effect of the artefenomel/FQ combination, by demonstrating a statistically significant relationship between artefenomel exposure and clinical efficacy. A relatively low dose of 400 mg of ferroquine (FQ) was tested alone, and in combination with 3 dose levels of artefenomel (300, 600 and 100 mg) to maximize the likelihood of demonstrating this relationship.</p>\n<p>\n Adults and adolescents aged 14 years to 69 years of age inclusive, who presented with uncomplicated <em>P. falciparum</em> malaria were recruited. Children aged <14 years were excluded from study to avoid administration of sub-therapeutic doses to the younger population which is inherently more susceptible to progression to severe malaria.</p>\n<p>\n Baseline parasitemia is a strong covariate of clinical efficacy with higher parasitaemia levels requiring higher drug exposure to achieve cure, therefore the entry criterion for baseline parasitaemia was restricted to patients with ≥3,000 to ≤50,000 asexual parasites/μL of blood by microscopy.</p>\n<p>\n Given that the study failed to show a statistically significant contribution of artefenomel to the effect of the combination, the results of Study ACT14655 provide learning for the design of future studies with this objective. The dose of the fixed component of the combination must be selected to achieve sufficiently low efficacy to ensure that the effect of the exposure of the partner drug on efficacy can be detected. Doses of the partner drug must span a wide range of exposures across the steep-part of the exposure-response curve, and simulation used to select the doses, and to estimate sample size must be based on populations with similar patient characteristics to the that to be recruited to the study.</p>\n<p>\n Finally, administration of significantly sub-therapeutic doses required the exclusion of clinically vulnerable patients (as was done in this study) and close monitoring of recruited patients to ensure rescue medication is administered when appropriate.</p>\n
      • quantity_imported279
      • quantity_dispensed36
      • quantity_destroyed279
      • quantity_exported0
      • balance_site 0
      • final_date0000-00-00
      • modified2021-03-23 11:45:35
      • created2018-05-31 14:59:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id434
        • application_id682
        • given_nameGRACE
        • middle_nameKIRINGA
        • family_nameKAGUTHI
        • qualificationMBchB
        • professional_addressKEMRI
        • telephone0729489743
        • emailskiringa@gmail.com
        • created2018-05-31 15:28:28
        • modified2018-08-10 09:49:29
    • SiteDetail(array)
      • 0(array)
        • id551
        • application_id682
        • county_id41
        • site_nameCenter for Respiratory Diseases Research
        • physical_addressSIAYA DISTRICT HOSPITAL
        • contact_detailsPostal Address: P.O. Box 76, Siaya 40600. Telephone: 0722-680162, 0713-989294.
        • contact_personDr grace K. Kaguthi
        • site_capacity(null)
        • misc(null)
        • created2018-05-31 15:28:28
        • modified2018-08-10 09:49:29
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id566
        • application_id682
        • county_id42
        • site_nameKEMRI
        • physical_addressCDC KISUMU
        • contact_detailsP.O Box 20778-00202 Nairobi. Tel: +254 020 2726781, +254 020 2722541, +254 020 2713349, 0722205901, 0733400003.
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2018-08-06 15:12:46
        • modified2018-08-10 09:49:29
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id344
        • application_id682
        • sponsorSanofi-aventis Recherché et Développement
        • sponsor_type(null)
        • contact_personTirhani Maluleke
        • addresssanofi-aventis south Africa (pty) ltd sanofi-aventis house 2 Bond Street Grand Central Ext 1 Midrand South Africa 1685
        • telephone_number27 11 847 5113
        • fax_number27 86 682 2257
        • cell_number27 82 455 0270
        • email_addressinfo@sanofi-aventis.com
        • created2018-05-31 15:28:28
        • modified2018-08-10 09:49:29
  • 3(array)
    • Application(array)
      • id746
      • user_id611
      • trial_status_id3
      • abstract_of_study<p>\n Plasmodium falciparum (P. falciparum) malaria remains a deadly endemic parasitic disease, with 212 million new cases and over 429,000 deaths reported in 2015. World Health Organization (WHO) guidelines recommend that artemisinin-based combination therapies (ACT) are used to treat uncomplicated P. falciparum malaria, which is administrated in a 3-day regimen. Sanofi and Medicines for Malaria Venture (MMV) are co-developing a fixed dose combination (FDC) of FQ and artefenomel (OZ439) for a single dose treatment of uncomplicated malaria in adults and children. Per Food and Drug Administration (FDA) guidance for co-development of 2 new investigational drugs for use in combination, it is recommended to demonstrate the contribution of each individual component to the effect of the combination. This phase 2a study will test clinical and parasiticidal activity, pharmacokinetics (PK) and safety of 3 doses of OZ439 associated with a fixed dose of FQ and FQ alone. This is a phase 2a, randomized, open label, parallel-group study, single-dose regimen, testing 3 dose levels of OZ439 given in combination with FQ and FQ alone in participants with uncomplicated P. falciparum malaria. The primary objective of the study is to show the contribution of OZ439 to the clinical and parasiticidal effect of OZ439/FQ combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the concentration time curve up to infinity (AUC) of OZ439 as PK predictor. Adults up to 69 years old and adolescents as of 14 years old will be included in 4 parallel arms in a 1:1:1:1 randomization ratio. Randomization will occur the day of or up to 1 day after screening procedures. Participants will receive one of the 4 treatments: FQ 400 mg alone or combined with OZ439 300 mg, 600 mg, or 1000 mg. Participants will be hospitalized for the first 48 hours or up to 4 days or longer upon investigator’s judgment. Participants will be screened sequentially as they present to the study facility to achieve 140 randomly assigned to study treatment and 120 evaluable participants for an estimated total of 30 evaluable participants per treatment group. Ahero site we will recruit about 40 patients both males and females. There will be 4 study groups receiving different doses of study drugs. The primary endpoint will be Day 28 PCR-corrected ACPR. The parasite clearance will be determined by microscopy and PK parameters will determined by chromatography techniques while safety parameters will be assessed by clinical evaluation during the study visits and clinical laboratory evaluations.</p>\n
      • study_title<p>\n A Randomized, Open label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel (OZ439) given in combination with Ferroquine (FQ) and FQ alone, in African Patients with Uncomplicated Plasmodium falciparum Malaria</p>\n
      • laymans_summary<p>\n Malaria remains a major public health with great impact on children and pregnant women. In 2015 World health Organization reported 212 million new cases and over 429,000 deaths. WHO currently recommends the use of artemisinin-based combination treatment (ACT) for uncomplicated <em>P. falciparum </em>malaria, administrated in a 3-day dose. However, there is already development of resistance to ACTs in South East Asia and there is worry that this will spread the rest of the world and there is need to develop new combinations treatment regimens for treatment of uncomplicated malaria. Therefore, Sanofi and Medicines for Malaria Venture (MMV) are co-developing a fixed dose combination (FDC) of FQ and artefenomel (OZ439) for a single dose treatment of uncomplicated malaria in adults and children. The study is going to be done in several countries where malaria is common and Kenya is one of them. The sample size will be140 patients with uncomplicated malaria. In Kenya the study will be conducted in Ahero and Siaya County hospitals. In Ahero we will recruit about 40 patients both males and females. The patients will have blood drawn from the arm to check the presence parasites in the blood, check the blood level, kidney, liver functions and drug blood level. The main outcome will be clearance of parasites and no recurrence of infection by 28 days after starting treatment. The potential risks are that this is a new drug and a patient can react to it but so far it has been safe in the previous studies. The other possible risks is that being a new it may not clear malaria infection but the patients will be followed up closely and in case of failure to respond to treatment they will be given rescue treatment. The study will be conducted in line with National and international guidelines for clinical trials. The study will be initiated once all the approvals have been obtained and the sponsor representatives initiates the study site. The data generated will be analysed as per the predesigned statistical analytical plan and will focus on the how well the drug clears malaria parasites from the patients’ blood, how the drug is safe and drug level in the patients’ blood. The results from this study will inform the development of this new treatment of uncomplicated malaria that is needed as there is already resistance to ACTs in Asia. The results from this study will be disseminated to stakeholders in Kisumu County, published in peer reviewed scientific journals, presented at Scientific conferences.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleA Randomized, Open, Parallel-group, Single Dose, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel in combination with Ferroquine (FQ) and FQ alone, in African Patients with Unc
      • protocol_noECCT/19/01/01
      • version_noVersion number: 1
      • date_of_protocol13-11-2017
      • study_drugOZ439 (artefenomel) and SSR97193 (ferroquine)
      • disease_conditionPlasmodium falciparum (P. falciparum) malaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid1
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameOZ439 and SSR97193
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressMshitindo@strathmore.edu
      • 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_countries1
      • 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_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantAMINA SALIM
      • declaration_date116-01-2019
      • declaration_principal_investigatorBERNHARDS OGUTU - PRINCIPAL INVESTIGATOR
      • declaration_date216-01-2019
      • placebo_presentNo
      • study_objectives<p>\n Primary</p>\n<p>\n  </p>\n<ul>\n <li>\n To show the contribution of OZ439 to the clinical and parasiticidal effect of OZ439/FQ combination by analyzing exposure-response of OZ439 measured by Day 28 PCR-corrected ACPR for the effect and the AUC of OZ439 as PK predictor</li>\n</ul>\n<p>\n  </p>\n<p>\n Secondary</p>\n<p>\n  </p>\n<ul>\n <li>\n To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR</li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints </li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone</li>\n</ul>\n<p>\n  </p>\n<p>\n To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood</p>\n<p>\n  </p>\n<p>\n Tertiary/exploratory</p>\n<p>\n  </p>\n<ul>\n <li>\n To explore the impact of study treatment on functional gametocytemia</li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n To evaluate the relationship between parasitemia and concentration of OZ439/FQ</li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n To evaluate the relationship between QTc and concentration of OZ439/FQ</li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n 11.0 INCLUSION CRITERIA Participants are eligible to be included in the study only if all of the following criteria apply: Age Participant must be 14 to 69 years of age inclusive, at the time of signing the informed consent. Type of participant and disease characteristics 1. Participants who present with uncomplicated P. falciparum malaria, with a fever as defined with axillary temperature ≥37.5 degree Celsius (°C) or oral/ rectal/ tympanic temperature ≥38°C or history of fever in the previous 24 hours (history of fever must be documented), with a mono-infection with P. falciparum and parasitemia (microscopically, blood smear) ≥3,000 and ≤50,000 asexual parasites/μL of blood. Weight Body weight within 35 and 90 kg (inclusive). Sex Male and female 1. Male participants: A male participant must agree to use contraception as detailed in Appendix 5 of this protocol for 3 months after the last dose of study treatment and refrain from donating sperm during this period. 2. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies: - Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR - A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 for 3 months after the last dose of study treatment. Informed Consent Capable of giving signed informed consent (if the patient is ≥age defining majority) as described in Appendix 3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Informed consent signed by the legally acceptable representative (LAR) of the minor patient (<18 years of age or</p>\n
      • principal_exclusion_criteria<p>\n 12.0 EXCLUSION CRITERIA Participants are excluded from the study if any of the following criteria apply: Medical conditions 1. Presence of severe malaria 2. Known history or evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, respiratory, endocrine, immunological, infectious, neurological (in particular convulsions), malignancy, psychiatric disease or symptoms which, in the judgment of the investigator, might confuse the interpretation of the safety information. 3. Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in the study or inability to tolerate oral treatment or severe diarrhea defined as 3 or more watery stools per day Severe malnutrition defined as body mass index of less than 16 kg/m² for adults and for children Z-score <-3 or weight for age (%) of the median <60. 4. Splenectomized participants or presence of surgical scar on left hypochondrium 5. Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other amino quinolines or to OZ439 or OZ277 or any of the excipients. Prior/concomitant therapy Participant treated with anti-malarial treatment: 1. With PQP-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine within the previous 6 weeks. 2. With amodiaquine or chloroquine within the previous 4 weeks. 3. With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial 4. treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days. 5. With any herbal products or traditional medicines, within the past 7 days 6. Previous treatment within 5 times the half-life or within the last 14 days, whichever the 7. longest, which are: strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but 8. inhibiting both CYP2C and CYP3A and/or CYP inducers (Appendix 6). Any treatment known to induce a prolongation of QT interval (Appendix 6) Prior/concurrent clinical study experience 1. Participated in any trial investigating OZ439 and/or FQ compounds 2. Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance 3. Enrolled in another clinical trial within the past 4 weeks or during the study period Diagnostic assessments 1. Mixed Plasmodium infection 2. Presence of Hepatitis A – immunoglobulin M (HAV-IgM), Hepatitis B surface antigen 3. (HBs Ag) or Hepatitis C virus antibody (HCV Ab) and/or known to have active Hepatitis 4. C virus RNA (HCV RNA) 5. Laboratory parameters with abnormalities deemed clinically significant by the investigator. 6. Abnormal LFT: aspartate transferase (AST) >2 upper limit of normal range (ULN), or alanine transferase (ALT) >2 ULN or total bilirubin >1.5 ULN 7. Positive pregnancy test at study screening for female participants of childbearing potential 8. QTcF >450 ms at screening or pre-dose 9. Hypokalemia (<3.5 mmol/L), hypocalcemia (<2.0 mmol/L) or hypomagnesemia (<0.5 mmol/L) at screening or pre-dose Other exclusions 1. Family history of sudden death or of congenital prolongation of the QT interval or known congenital prolongation of the QT-interval or any clinical condition known to prolong the QT interval e.g., participants with a history of symptomatic cardiac arrhythmias including atrial fibrillation (AF) or with clinically relevant bradycardia 2. Patient not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures or unable to drink.</p>\n
      • primary_end_points<p>\n 13.0 PRIMARY END POINTS. • To show the contribution of OZ439 to the clinical and parasiticidal effect of OZ439/FQ combination by analyzing exposure-response of OZ439 measured by Day 28 PCR-corrected ACPR for the effect and the AUC of OZ439 as PK predictor. • Day 28 PCR-corrected ACPR.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • 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 19.0 CAPACITY OF AHERO SITE NO NAME ROLE</p>\n<p>\n 1 Dr. Bernhards Ogutu PI (MBChB, MMED ,PhD)</p>\n<p>\n 2 DR. John Michael Ongecha Sub I (MSc ,PhD Immunology)</p>\n<p>\n 3 Dr. Fredrick Olewe Sub I (MBChB)</p>\n<p>\n 4 Nelly Koskei Clinical Research Coordinator</p>\n<p>\n 5 Agnes Onyango Nurse</p>\n<p>\n 6 Maureen Mbija Nurse</p>\n<p>\n 7Mary Atieno Nurse</p>\n<p>\n 8 Jael Aran Nurse</p>\n<p>\n 9 Wycliff Misiayi Nurse</p>\n<p>\n 10 Winny Chepkemoi Clinical Officer</p>\n<p>\n 11 Hellen Nyangasi Clinical Officer</p>\n<p>\n 12 Solomon Otieno Clinical Officer</p>\n<p>\n 13 Kennedy Ogweno Laboratory Technologist</p>\n<p>\n 14 Festus Okute Microscopist</p>\n<p>\n 15 Grace Owino Laboratory Technologist</p>\n<p>\n 16 Cornel Arima Laboratory technologist</p>\n<p>\n 17 Dr. Ruth Wasuna Pharmacist</p>\n<p>\n 18 Mathew onyango Pharmaceutical technologist</p>\n<p>\n 19 Fredrick Otieno Field Coordinator</p>\n<p>\n 20 Florence Amollo Community Health Worker</p>\n<p>\n Ahero Clinical trials Unit is situated within Ahero County Hospital. It has a 7 bed capacity ward for study participants, Laboratory and pharmacy. There is an emergency tray within the wards. All participants who need further medical attention are referred to Jaramogi Oginga Odinga teaching and Referral Hospital.</p>\n
      • other_details_explanation<p>\n Europe is a non-endemic Malaria zone. There are only imported malaria cases in Europe. In France, 3,560 imported cases were reported in 2011.Source: https://www.pasteur.fr/en/medical-center/disease-sheets/malaria</p>\n<p>\n France is a non-endemic malaria zone. WHO report (2016): http://apps.who.int/iris/bitstream/10665/254913/1/WHO-HTM-GMP-2017.4-fre.pdf?ua=1</p>\n
      • other_details_regulatory_notapproved<p>\n Uganda submitted to NDA 11 December 2018, outcome pending</p>\n
      • other_details_regulatory_approved<p>\n The Scientific and Ethics Review Unit (SERU) - KEMRI</p>\n
      • other_details_regulatory_rejected<ol>\n <li>\n Benin submitted 15 February 2018, Approval 25 Sept 2018 (1 site)</li>\n <li>\n Burkino-Faso – 16 April 2018, approved 25 May 2018 (2 sites)</li>\n <li>\n Gabon submitted 14 June 2018, approved 19 June 2018 (2 sites)</li>\n <li>\n Kenya submitted 17 May 2018, approved 03 October 2018 (1 site – Dr Kaguthi)</li>\n</ol>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration1 Year
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNot applicable
      • 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_states5
      • number_of_sites2
      • multi_country_listBenin, Gabon, Kenya, Uganda, Burkina Faso
      • data_monitoring_committeeYes
      • total_enrolment_per_site40 (Ahero)
      • total_participants_worldwide140
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • 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_nameBernhards
      • investigator1_middle_nameOgutu
      • investigator1_family_nameRagama
      • investigator1_qualification MBChB, MMED, PhD
      • investigator1_professional_addressP.O. BOX 54 KISUMU
      • investigator1_telephone+254 733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_No
      • number_participants40 (Ahero)
      • notification
      • approval_date13-08-2019
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted13-05-2020
      • 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)
      • modified2024-01-19 16:57:39
      • created2019-01-07 11:14:08
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id466
        • application_id746
        • given_nameBernhards
        • middle_nameOgutu
        • family_nameRagama
        • qualificationMBChB, MMED, PhD
        • professional_addressP.O. BOX 54 KISUMU
        • telephone+254 733812613
        • emailogutu6@gmail.com
        • created2019-01-07 11:46:21
        • modified2020-05-13 16:57:58
    • SiteDetail(array)
      • 0(array)
        • id588
        • application_id746
        • county_id42
        • site_nameAhero County hospital
        • physical_addressNext To Ahero Police Station, Along Kisumu - Busia Road, Ahero
        • contact_details+254727863357/ 737183162
        • contact_personFred Olewe
        • site_capacity(null)
        • misc(null)
        • created2019-01-07 11:46:21
        • modified2020-05-13 16:57:58
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id589
        • application_id746
        • county_id41
        • site_nameSiaya County Hospital
        • physical_addressn/a
        • contact_detailsn/a
        • contact_personn/a
        • site_capacity(null)
        • misc(null)
        • created2019-01-07 12:25:59
        • modified2020-05-13 16:57:58
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id363
        • application_id746
        • sponsor Sanofi-Aventis R&D
        • sponsor_typeIndustry
        • contact_personTherese Sylvester
        • addresssanofi-aventis South Africa (Pty) Ltd Sanofi House, 44 on Grand Central Office Park, 2 Bond Street, Grand Central Extension 1, Midrand 1685
        • telephone_number+1.330.278.9251
        • fax_numberN/A
        • cell_number+1.330.278.9251
        • email_addresstsylvester@icongphs.com
        • created2019-01-07 11:46:21
        • modified2020-05-13 16:57:58
  • 4(array)
    • Application(array)
      • id1448
      • user_id659
      • trial_status_id(null)
      • abstract_of_study<p>\n <strong><u>Trial Design:</u></strong></p>\n<p>\n This will be a multicenter, open-label, randomized, parallel-group, non-inferiority study in adults and children with uncomplicated P. falciparum malaria (P. falciparum with or without other Plasmodium spp. co-infection). After completion of the Core phase of the study, patients may enter in the Extension phase (single-group).</p>\n<p>\n <strong><u>Purpose:</u></strong></p>\n<p>\n This study aims to confirm the efficacy, safety and tolerability of KLU156, a fixed dose combination of ganaplacide (KAF156) and a solid dispersion formulation of lumefantrine (lumefantrine-SDF), when administered once daily for three days in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection).</p>\n<p>\n In the Extension phase, the safety, tolerability and efficacy of repeated treatment with KLU156 will be assessed for a maximum of two years in patients who did not experience early treatment failure (ETF), who did not experience any study treatment-related SAE (Serious Adverse Event) previously and who gave informed consent to participate in the Extension phase</p>\n<p>\n <strong><u>Study Rationale:</u></strong></p>\n<p>\n This Phase 3 study includes a Core phase and an Extension phase.</p>\n<p>\n The Core phase of this study aims to confirm the efficacy, safety and tolerability of KLU156, a fixed dose combination of ganaplacide (KAF156) and a solid dispersion formulation of lumefantrine (lumefantrine-SDF), when administered once daily for 3 days in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection) in order to support marketing authorization application for KLU156. There is an unmet medical need for anti-malarial combination treatment including a partner drug with a new mechanism of action to counter the emergence of resistance to artemisinin.</p>\n<p>\n The Extension phase is designed to assess the safety, tolerability and efficacy of repeated treatment with KLU156 for a maximum of two years in patients who have completed the Core phase without experiencing early treatment failure (ETF) nor any study treatment-related SAE and who consent to participate in the Extension phase.</p>\n<p>\n  </p>\n<p>\n <strong><u>P</u></strong><strong><u>rimary objective(s) </u></strong></p>\n<p>\n ● Core phase:</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n To confirm the efficacy of KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P.falciparum (with or without other Plasmodium spp. coinfection) by demonstrating that KLU156 is noninferior to Coartem (non‑inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29.</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong><u>Secondary objective(s)</u></strong></p>\n<p>\n ● Core phase:</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Key secondary objective: To further confirm the efficacy of KLU156 by demonstrating non-inferiority of KLU156 to Coartem (NI margin 7.5%) based on the uncorrected ACPR at Day 29</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong><u>●</u></strong><strong><u> Extension phase:</u></strong></p>\n<ul style=\"list-style-type:circle;\">\n <li>\n To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by <em>P. falciparum </em>(with or without other <em>Plasmodium </em>spp<em>. </em>co-infection) for a maximum of 2 years.</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To evaluate efficacy over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by <em>P. falciparum </em>(with or without other <em>Plasmodium </em>spp<em>. </em>co-infection) for a maximum of 2 years.</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong><u>Exploratory objective(s)</u></strong></p>\n<p>\n ● <strong>Core phase:</strong></p>\n<ul style=\"list-style-type:circle;\">\n <li>\n To explore the transmission-blocking activity of KLU156 (direct membrane feeding assay (DMFA)) at selected sites</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To quantify parasites that are below the detection level of microscopy using quantitative PCR (qPCR) as a diagnostic tool.</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To explore the impact of PCR methods on efficacy estimates.</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To assess <em>in vitro </em>susceptibility profile of tested parasites at selected sites (if feasible).</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To assess the effect of the main ADME gene factors on ganaplacide PK at selected sites (if feasible).</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To assess the pharmacokinetics of ganaplacide and lumefantrine in malaria patients.</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n To explore the acceptability, palatability and ease of administration of KLU156.</li>\n</ul>\n<p>\n Ø  To explore the emergence of drug resistance markers and the relationship between parasite genotypes of interest and parasite clearance kinetics/efficacy.</p>\n<p>\n  </p>\n<p>\n ● <strong>Extension phase:</strong></p>\n<p>\n Ø  To assess the efficacy over repeated treatment with KLU156.</p>\n<p>\n To explore the emergence and/or selection of drug resistance markers and the relationship between parasite genotypes of interest and parasite clearance kinetics/efficacy, upon repetitive treatment.</p>\n<p>\n  </p>\n<p>\n <strong>Study Population:</strong></p>\n<p>\n The study population will consist of male and female patients ≥ 5 kg of body weight and ≥ 2 months of age with confirmed uncomplicated <em>P. falciparum </em>malaria. Only patients with malaria symptoms and a <em>P. falciparum </em>count ≥ 1,000 parasites/μL and ≤ 200,000 parasites/μL (with or without other <em>Plasmodium </em>spp. co-infection) will be included in the study. Approximately 1,500 patients will be enrolled in the study (see <strong><u>Section 9.9 of the Protocol v00</u></strong> for more details on sample size determination).</p>\n
      • study_title<p>\n A randomized, open-label, multicenter study to compare efficacy, safety and tolerability of KLU156 with Coartem® in the treatment of uncomplicated Plasmodium falciparum malaria in adults and children ≥ 5 kg body weight followed by an Extension phase with repeated KLU156 treatment </p>\n
      • laymans_summary<p>\n Analysis of the efficacy, safety and tolerability of a new combination of ganaplacide and lumefantrine in adults and children with uncomplicated malaria</p>\n
      • short_titleKALUMA Study
      • protocol_noECCT/24/08/06
      • version_no00
      • date_of_protocol14-06-2022
      • study_drugKLU156 (Ganaplacide/Lumefantrine Solid Dispersion Formulation)
      • disease_conditionUncomplicated Plasmodium falciparum malaria
      • 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_nameKLU156 (Ganaplacide/Lumefantrine Solid Dispersion Formulation)
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameCoartem/Riamet Dispersible & Comparator. Coartem/Riamet 80/480mg
      • comparator_registeredyes
      • comparator_countriesCountry Local Brand Name Marketing Authorization Holder – Company name \nBenin Coartem Novartis Pharma AG \nBotswana Riamet Novartis Pharma Services AG \nBurkina Faso Coartem Novartis Pharma AG \nCameroon Coartem Novartis Pharma AG \nCongo (Brazzaville) Coartem Novartis Pharma AG \nCongo, Democratic Republic Coartem Novartis Pharma AG \nEthiopia Coartem Novartis Pharma Schweiz AG \nGabon Coartem Novartis Pharma AG \nGhana Coartem Novartis Pharma Services AG \nGuinea Coartem Novartis Pharma AG \nIvory Coast Coartem Novartis Pharma AG \nKenya Coartem NVS Kenya Ltd \nLiberia Coartem Novartis Pharma Services AG \nMadagascar Riamet Novartis Pharma Services AG \nMalawi Riamet Novartis Pharma Services AG \nMali Coartem Novartis Pharma AG \nMozambique Riamet Medis Farmaceutica Lda \nNamibia Coartem Novartis Pharma Services AG \nNiger Coartem Novartis Pharma AG \nNigeria Coartem Novartis Nigeria Limited \nSenegal Coartem Novartis Pharma AG \nSudan Coartem Novartis Pharma Schweiz AG \nTanzania Riamet NVS Kenya Ltd \nTogo Coartem Novartis Pharma AG \nUganda Riamet NVS Kenya Ltd \nZambia Riamet Novartis Pharma Services AG \nZimbabwe Riamet Novartis Pharma Services AG \n
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressraps.clinicaltrials@novartis.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_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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDenish Maisiba
      • declaration_date121-08-2024
      • declaration_principal_investigatorBernhards Ogutu
      • declaration_date221-08-2024
      • placebo_presentNo
      • study_objectives<p>\n <strong><u>P</u></strong><strong><u>rimary objective(s) </u></strong></p>\n<p>\n ● Core phase:</p>\n<p>\n Ø  To confirm the efficacy of KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P.falciparum (with or without other Plasmodium spp. coinfection) by demonstrating that KLU156 is noninferior to Coartem (non‑inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29.</p>\n<p>\n  </p>\n<p>\n <strong><u>Secondary objective(s)</u></strong></p>\n<p>\n ● Core phase:</p>\n<p>\n Ø  Key secondary objective: To further confirm the efficacy of KLU156 by demonstrating non-inferiority of KLU156 to Coartem (NI margin 7.5%) based on the uncorrected ACPR at Day 29</p>\n<p>\n Ø  To confirm the efficacy of KLU156 by assessing uncorrected and PCR-corrected ACPR at additional time points, as well as fever and parasite clearance times (FCT and PCT), gametocyte carriage over time between the two treatment arms.</p>\n<p>\n Ø  To compare the safety and tolerability profile of the two treatment arms on AEs, general laboratory, vital signs and ECG measurements.</p>\n<p>\n  </p>\n<p>\n ● <strong>Extension phase:</strong></p>\n<p>\n Ø  To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by <em>P. falciparum </em>(with or without other <em>Plasmodium </em>spp<em>. </em>co-infection) for a maximum of 2 years.</p>\n<p>\n Ø  To evaluate efficacy over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by <em>P. falciparum </em>(with or without other <em>Plasmodium </em>spp<em>. </em>co-infection) for a maximum of 2 years.</p>\n<p>\n  </p>\n<p>\n <strong><u>Exploratory objective(s)</u></strong></p>\n<p>\n  </p>\n<p>\n ● <strong>Core phase:</strong></p>\n<p>\n Ø  To explore the transmission-blocking activity of KLU156 (direct membrane feeding assay (DMFA)) at selected sites</p>\n<p>\n Ø  To quantify parasites that are below the detection level of microscopy using quantitative PCR (qPCR) as a diagnostic tool.</p>\n<p>\n Ø  To explore the impact of PCR methods on efficacy estimates.</p>\n<p>\n Ø  To assess <em>in vitro </em>susceptibility profile of tested parasites at selected sites (if feasible).</p>\n<p>\n Ø  To assess the effect of the main ADME gene factors on ganaplacide PK at selected sites (if feasible).</p>\n<p>\n Ø  To assess the pharmacokinetics of ganaplacide and lumefantrine in malaria patients.</p>\n<p>\n Ø  To explore the acceptability, palatability and ease of administration of KLU156.</p>\n<p>\n Ø  To explore the emergence of drug resistance markers and the relationship between parasite genotypes of interest and parasite clearance kinetics/efficacy.</p>\n<p>\n  </p>\n<p>\n ● <strong>Extension phase:</strong></p>\n<p>\n Ø  To assess the efficacy over repeated treatment with KLU156.</p>\n<p>\n To explore the emergence and/or selection of drug resistance markers and the relationship between parasite genotypes of interest and parasite clearance kinetics/efficacy, upon repetitive treatment</p>\n
      • principal_inclusion_criteria<p>\n <strong>Key Inclusion criteria (Core phase):</strong></p>\n<p>\n 1. Male or female patients ≥ 5 kg of body weight and ≥ 2 months of age</p>\n<p>\n 2. Microscopically confirmed diagnosis of uncomplicated <em>P. falciparum </em>malaria with an asexual <em>P. falciparum </em>parasitemia ≥ 1,000 and ≤ 200,000 parasites/μL at the time of pre-screening with or without other <em>Plasmodium </em>spp. co-infection.</p>\n<p>\n 3. Axillary temperature ≥ 37.5 ºC or oral temperature ≥ 38.0 ºC or tympanic/rectal temperature ≥ 38.5 ºC; or history of fever during the previous 24 hours (at least documented verbally)</p>\n<p>\n 4. Negative pregnancy test for patients of childbearing potential</p>\n<p>\n 5. Signed informed consent must be obtained before any assessment is performed; for minors, signed informed consent must be obtained from parent/legal guardian. If the parent/legal guardian is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients who are capable of providing assent, must provide it along with parent/legal guardian consent or as per local ethical standards</p>\n<p>\n 6. The patient and/or their parent/legal guardian is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.</p>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n <strong>Key Exclusion criteria (Core phase)</strong></p>\n<p>\n 1. Signs and symptoms of severe malaria according to WHO 2015 (World Health Organization)</p>\n<p>\n 2. Concurrent febrile illnesses (e.g., typhoid fever, known or suspected dengue fever, known COVID19)</p>\n<p>\n 3. Severe malnutrition. For patients ≥ 12 years: body mass index (BMI) < 16.0. For children < 12 years: less than 70% of median normalized WHO reference weight or very low midupper arm circumference (MUAC < 115 mm)</p>\n<p>\n 4. Repeated vomiting (defined as > 3 times in the 24 hours prior to start of screening) or severe diarrhea (defined as > 3 watery stools in the 24 hours prior to start of screening)</p>\n<p>\n 5. Clinically relevant abnormalities of electrolyte balance which require correction, e.g.,hypokalemia, hypocalcemia or hypomagnesemia</p>\n<p>\n 6. Anemia (hemoglobin level <7 g/dL)</p>\n<p>\n 7. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (e.g., Human immunodeficiency virus (HIV) patients on antiretroviral therapy (ART) or tuberculosis (TB) patients on treatment),</p>\n<p>\n or which may jeopardize the patient in case of participation in the study.</p>\n<p>\n 8. Any of the following:</p>\n<p style=\"margin-left:.2in;\">\n • Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT) > 3 x the upper limit of normal (ULN), regardless of the</p>\n<p style=\"margin-left:.2in;\">\n     level of total bilirubin</p>\n<p style=\"margin-left:.2in;\">\n • Total bilirubin > 3 x ULN</p>\n<p style=\"margin-left:.2in;\">\n • Resting QT interval corrected by Fridericia’s formula (QTcF) > 450 ms at screening</p>\n<p>\n 9. Prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five plasma half-lives (or within 4 weeks of screening if half-life is unknown)</p>\n<p>\n 10. History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease</p>\n<p>\n 11. Pregnant or nursing (lactating) patients.</p>\n<p>\n  </p>\n
      • primary_end_points<p>\n <strong><u>Endpoint(s) for primary objective(s)</u></strong></p>\n<p>\n PCR-corrected adequate clinical and parasitological response (ACPR) at Day 29 (i.e., 28 days post-first</p>\n<p>\n dose administration)</p>\n<p>\n  </p>\n<p>\n <strong><u>Endpoint(s) for secondary objective(s)</u></strong></p>\n<p>\n <strong>Core Phase</strong>:</p>\n<p>\n  </p>\n<p>\n Ø  Uncorrected ACPR at Day 29</p>\n<p>\n Ø  PCR-corrected and uncorrected ACPR at Days 22 and 43 (i.e., 21 and 42 days post-first dose administration). Incidence rate of recrudescence and new infection at Days 22, 29 and 43. Parasite and Fever Clearance Times. Proportion of patients with parasitemia at 12, 24, 48 and 72 h after treatment. Disappearance or development of gametocytemia in patients with or without gametocytemia at baseline (pre-first dose administration), respectively.</p>\n<p>\n Ø  Standard safety/tolerability assessments: Adverse event (AE)/serious adverse event (SAE) incidence and severity, laboratory abnormalities and ECG abnormalities.</p>\n<p>\n  </p>\n<p>\n <strong>Extension Phase:</strong></p>\n<p>\n Ø  KLU156-related AE/SAE incidence and severity by malaria episode. AE/SAE incidence and severity, laboratory abnormalities and ECG abnormalities by malaria episode.</p>\n<p>\n Ø  PCR-corrected and uncorrected ACPR at Day 29 by malaria episode. Gametocyte carriage over time by malaria episode.</p>\n<p>\n  </p>\n<p>\n <strong><u>Endpoint(s) for exploratory objective(s)</u></strong></p>\n<p>\n <strong>Core Phase</strong>:</p>\n<p>\n  </p>\n<p>\n Ø  Direct membrane feeding assay will be performed at selected sites to assess the transmission-blocking activity by determining oocyst density and infection prevalence in female <em>Anopheles gambiae </em>mosquito colonies.</p>\n<p>\n Ø  Presence of sub-microscopic density of <em>P.falciparum </em>asexual forms at baseline, Day 1 (6h, 12h), Day 2 (24h, 36h), Day 3 (48h), Days 4, 22, 29, and 43, parasite clearance time using qPCR.</p>\n<p>\n Ø  Proportion of patients with PCR corrected and uncorrected ACPR at Days 22, 29 and 43 using different parasite genotyping methods and algorithms.</p>\n<p>\n Ø  Parasite susceptibility to ganaplacide and lumefantrine <em>in vitro</em>.</p>\n<p>\n Ø  Associations between ganaplacide Day 8 levels and pharmacogene Open Reading Frame (ORF) Diversity.</p>\n<p>\n Ø  Drug concentration at 48 h, 54 h and 168 h.</p>\n<p>\n Ø  Response to questionnaire of acceptability, palatability and ease of administration.</p>\n<p>\n Ø  Presence of parasite specific gene mutations (<em>pfmdr1, pfcrt, pfkelch13, pfcarl</em>, <em>pfugt </em>and additional parasite genes of interest).</p>\n<p>\n  </p>\n<p>\n <strong>Extension Phase:</strong></p>\n<p>\n Ø  Incidence rate of recrudescence and new infections at Day 29 by malaria episode. Incidence rate of malaria episode for a maximum of 2 years.</p>\n<p>\n Presence of parasite specific gene mutations (<em>pfmdr1, pfcrt, pfkelch13, pfcarl</em>, <em>pfugt </em>and additional parasite genes of interest) along the time of trial</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyTolerability
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong><u>Site 1600:</u></strong></p>\n<p>\n KEMRI/CGHR- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya, Off Kisumu-Busia Road, P.O.Box 1578- 40100, Kisumu</p>\n<p>\n The Siaya County Referral Hospital Clinical Research Center</p>\n<p>\n The KEMRI/Centre for Global Health Research facility is situated with the Siaya County Referral Hospital (SCRH). The SCRH is the largest hospital in Siaya County, western Kenya and is designed for care and treatment of all medical (pediatric and adult), surgical and obstetric patients, both in the outpatient and inpatient settings. This is a level four referral facility that provides healthcare to the general public in the whole of Siaya County and some adjacent counties - Busia, Vihiga and Kisumu.</p>\n<p>\n The hospital has a total bed capacity of 420 patients that include 50 in the pediatric inpatient ward and 100 in the adult medical wards (both male and female wards). Additional special units in addition to the traditional inpatient wards include a Renal/Dialysis unit and an intensive care unit with bed capacities of 5 each. Currently, the ICU has only 2 functional beds/ventilators in operation. The hospital is staffed by consultant doctors in all the general disciplines, medical officers, Pharmacists, Dentists, clinical officers, nurses, radiographers and sonographers, laboratory and pharmaceutical technologists. The specialist doctors include two Pediatricians, two Physicians/Internists, three Surgeons, one Psychiatrist, one psychologist and an Obstetrician/Gynecologist.</p>\n<p>\n The site has a waste disposal policy and this in in line with the regulatory requirements of the hospital. There is also a quality assurance policy which is implemented at the hospital according to ISO standards. The hospital has an ISO-accredited laboratory capable of carrying routine tests including biochemistry, hematology, microbiology and basic microscopy.</p>\n<p>\n <strong><u>Site 1601:</u></strong></p>\n<p>\n Kombewa Clinical Research Centre, Off Kisumu-Bondo Road, Opposite Kombewa County Hospital,</p>\n<p>\n P.O. Box 54-40100, Kisumu Kenya</p>\n<p>\n Kombewa CRC has adequate staff and facilities to conduct the trial. The site has the following cadres of staff; 4 pediatrician, 4 medical offices, 1 regulatory officer, 5 study coordinators, 6 clinical officers, 7 Lab technologist, 9 nurses, 1 pharmacist, 2 pharmaceutical technologist, 6 data clerks and 38 filed workers. The unit has two storey building consisting of office space, laboratory, clinical rooms, pharmacy, emergency room, observation room and records storage rooms.</p>\n<p>\n  </p>\n<p>\n <strong><u>Site 1602</u></strong>:</p>\n<p>\n Ahero Clinical Trials Unit. P.O.BOX 54-40100 Kisumu-Kenya</p>\n<p>\n  </p>\n<p>\n Ahero Clinical Trials Unit site is located within the Ahero county hospital in Nyando Sub- County, Kisumu County. Ahero County Hospital is level 4 hospital, with a bed capacity of 40, which receives referral from surrounding peripheral health facilities within Nyando Sub County and is able to accommodate both outpatient and in-patient adults and pediatric patients for several days.</p>\n<p>\n Staffing [ Human Workforce]</p>\n<p>\n The hospital has a total staff of over 100 health workers including, 2 Medical Officers,15 Clinical Officers,1 Pharmacist, 6 pharmaceutical technologists, Laboratory technologists and 40 Nurses.</p>\n<p>\n The Study Site in addition has: 2 Pediatricians,1 Medical Officer,3 Clinical officers,6 nurses,2 Pharmacist ,1 Pharmaceutical technologist ,1 Pharmaceutical technician, 1Field Coordinator, 2 Field Supervisors, 22 Community health workers, 1Data Manager,4 Data Clerks, 5 Laboratory technologist ,1 laboratory technician and microscopists with certificate for malaria microscopy proficiency testing (PT), regulatory officers, quality assurance officers and administrative officer. Some of our investigators are also part of Ethical Committee at SERU.</p>\n<p>\n  </p>\n<p>\n <strong><u>Institutional facilities</u></strong></p>\n<p>\n Ahero Clinical Trials Unit which is within the Ahero County Hospital is mainly used for research related activities including clinical trials. It holds clinical rooms, emergency room with a fully equipped crash cart, temperature-controlled pharmacy and laboratory, data room with stable internet connectivity for 24hours, Active Archival storage space and monitoring room.</p>\n<p>\n There are also several facilities within the hospital, which complement research activities. These include:</p>\n<p>\n •An ISO 15189:2012 accredited laboratory which is well-equipped and that handles both routine and specialized tests including, biochemistry, hematology and microbiology.</p>\n<p>\n •Adult and Pediatric wards that can accommodate any admission referral from the study</p>\n<p>\n •Vital signs equipment is available in both the out-patient and in-patient departments and at the Ahero Clinical Trials Unit site. The study site has also 1 ECG machine as well.</p>\n<p>\n •Continuous supply of oxygen from commercial supply from bulk oxygen cylinder.</p>\n<p>\n  </p>\n<p>\n <strong><u>Waste Management and Handling.</u></strong></p>\n<p>\n The site has established protocols for waste handling and disposal. This is based on sorting the</p>\n<p>\n waste according to the different biohazard level. The waste is then disposed according to protocol.</p>\n<p>\n There is an incinerator at the hospital to assist in the proper destruction and disposal of the waste.</p>\n<p>\n  </p>\n<p>\n <strong><u>Quality assurance policies and protocols.</u></strong></p>\n<p>\n The site has quality assurance SOPs that it follows for all its procedures. The staff are well trained</p>\n<p>\n and refresher courses are offered on a regular basis. Quality control / quality assurance checks and</p>\n<p>\n source data verification happens on the three major levels:</p>\n<p>\n Level 1 – Self Quality Check: Done on completion of study procedures while still seated with the</p>\n<p>\n participant</p>\n<p>\n Level 2 – Quality Control Check: Which entails QC checks that will be performed by the clinic</p>\n<p>\n QA officer/MO/SSC on a real-time basis and any errors picked will be addressed there and then.</p>\n<p>\n Level 3 – Quality Assurance Check: Done level are done at the data entry center by the data entry</p>\n<p>\n team during the receiving of the data from the field, clinics and during entry into the data base</p>\n<p>\n system to assure completeness and legibility.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span class=\"normaltextrun\"><span style=\"font-size: 9pt; line-height: 107%; font-family: Calibri, sans-serif; color: black; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;\">Malaria is not endemic in Switzerland. Hence, the trial cannot be conducted in Switzerland.</span></span><span class=\"eop\"><span style=\"font-size: 9pt; line-height: 107%; font-family: Calibri, sans-serif; color: black; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;\"> </span></span></p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n <strong>Country</strong></p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n <strong>Agency</strong></p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n <strong>HA submission Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;height:20px;\">\n <p>\n Burkina Faso</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n ANRP</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n 17-Oct-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p>\n Gabon</p>\n </td>\n <td style=\"width:160px;\">\n <p>\n ANMAPS</p>\n </td>\n <td style=\"width:160px;\">\n <p>\n 15-May-2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;height:20px;\">\n <p>\n Ghana</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n Ghana FDA</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n 10-Nov-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;height:20px;\">\n <p>\n Rwanda</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n Rwanda FDA</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n 03-May-2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;height:20px;\">\n <p>\n Uganda</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n NDA</p>\n </td>\n <td style=\"width:160px;height:20px;\">\n <p>\n 25-Oct-2023</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>Country</strong></p>\n </td>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>HA approval</strong></p>\n </td>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>No. of sites</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;\">\n <p>\n DRC</p>\n </td>\n <td style=\"width:213px;\">\n <p>\n 30-Oct-2023</p>\n </td>\n <td style=\"width:213px;\">\n <p>\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:20px;\">\n <p>\n India</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 20-Feb-2024</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:22px;\">\n <p>\n Ivory Coast</p>\n </td>\n <td style=\"width:213px;height:22px;\">\n <p>\n 25-Apr-2024</p>\n </td>\n <td style=\"width:213px;height:22px;\">\n <p>\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:20px;\">\n <p>\n Niger</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 07-Mar-2024</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 1</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:20px;\">\n <p>\n Nigeria</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 24-May-2024</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 1</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:20px;\">\n <p>\n Tanzania</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 27-May-2024</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 3</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:20px;\">\n <p>\n Mali</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 18-Mar-2024</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 1</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:20px;\">\n <p>\n Burkina Faso</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 15-Jan-2024</p>\n </td>\n <td style=\"width:213px;height:20px;\">\n <p>\n 1</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>Country</strong></p>\n </td>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>Reason for rejection</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;\">\n <p>\n N/A</p>\n </td>\n <td style=\"width:213px;\">\n <p>\n  N/A</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_halted<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>Country</strong></p>\n </td>\n <td style=\"width:213px;\">\n <p align=\"center\">\n <strong>Reason for halt of trial</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:213px;\">\n <p>\n N/A</p>\n </td>\n <td style=\"width:213px;\">\n <p>\n N/A</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • estimated_durationThe study duration will be 43 days (Core phase) plus 24 months (Extension phase).
      • 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_comparatorCoartem/Riamet
      • 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_states15
      • number_of_sites3
      • multi_country_listBurkina Faso\nIvory Coast\nGabon\nGhana\nIndia\nKenya\nMali\nMozambique\nNiger\nRwanda\nTanzania\nZambia\nDRC\nUganda\nNigeria\n
      • data_monitoring_committeeYes
      • total_enrolment_per_siteA maximum of 60 patients per site across all 3 sites
      • total_participants_worldwideApproximately 1,500 patients
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • 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_consentYes
      • subjects_specifyminors (Children from 2 to 12 years of age) require Legal Guardian / parental signature and approval
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationM Med
      • investigator1_professional_addressStrathmore University – CREATES
      • investigator1_telephone254733966065
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_No
      • number_participants180
      • notification
      • approval_date26-01-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted22-08-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted22-08-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-17 21:02:26
      • created2024-07-26 13:38:14
      • total_sites3
      • ecitizen_invoice322282
    • InvestigatorContact(array)
      • 0(array)
        • id1116
        • application_id1448
        • given_nameDr Patricia
        • middle_nameOdera
        • family_nameOjwang
        • qualificationMBChB, Master of Medicine in Paediatrics and Child health
        • professional_addressKEMRI/CGHR- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya,
        • telephone254 720 487 325
        • emailpattojey@gmail.com or pojwang@kemri.go.ke
        • created2024-07-26 14:27:37
        • modified2024-10-29 11:19:44
      • 1(array)
        • id1119
        • application_id1448
        • given_nameDr. Bernhards
        • middle_name
        • family_nameOgutu
        • qualificationMBChB, MMED Paediatrics and Child health
        • professional_addressKombewa Clinical Research Centre, Off Kisumu-Bondo Road, Opposite Kombewa County Hospital,
        • telephone+254 733 811613 or +254 733 333530
        • emailOgutu6@gmail.com
        • created2024-07-30 03:16:28
        • modified2024-10-29 11:19:44
      • 2(array)
        • id1120
        • application_id1448
        • given_nameDr.Bernhards
        • middle_name
        • family_nameOgutu
        • qualificationMBChB, MMED Paediatrics and Child health
        • professional_addressAhero Clinical Trials Unit. P.O.BOX 54-40100 Kisumu-Kenya
        • telephone+254 733 811613 or +254 733 333530
        • emailOgutu6@gmail.com
        • created2024-07-30 03:16:28
        • modified2024-10-29 11:19:44
    • SiteDetail(array)
      • 0(array)
        • id1758
        • application_id1448
        • county_id41
        • site_nameSite 1600: Kenya Medical Research Institute/Centre for Global Health Research Siaya
        • physical_addressOff Kisumu-Busia Road, Kisumu
        • contact_detailsPhone number: +254 720 487 325 P.O.Box 1578- 40100,
        • contact_personDr. Patricia Ojwang or Dr. Simon Kariuki
        • site_capacity(null)
        • misc(null)
        • created2024-07-26 14:27:37
        • modified2024-10-29 11:19:44
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id1760
        • application_id1448
        • county_id42
        • site_nameSite 1601:Kombewa Clinical Research Centre
        • physical_addressOff Kisumu-Bondo Road, Opposite Kombewa County Hospital, Kisumu Kenya
        • contact_detailsPhone Number: +254 733 811613 or +254733333530 22 P.O. Box 54-40100
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2024-07-30 03:39:20
        • modified2024-10-29 11:19:44
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1761
        • application_id1448
        • county_id42
        • site_nameAhero Clinical Trial Unit
        • physical_addressKisumu -Kenya
        • contact_detailsPhone Number: +254704616214 P.O.BOX 54-40100
        • contact_personDr. Bernhards Ogutu Dr. John Orimbo
        • site_capacity(null)
        • misc(null)
        • created2024-07-30 03:39:20
        • modified2024-10-29 11:19:44
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id766
        • application_id1448
        • sponsorNovartis Pharma AG
        • sponsor_typeIndustry
        • contact_personDr. Yannick Brunner
        • addressNovartis Campus Lichtstrasse 35 CH-4056 Basel Switzerland
        • telephone_number0041 76 360 56 97
        • fax_number
        • cell_number0041 76 360 56 97
        • email_addressyannick.brunner@novartis.com
        • created2024-07-26 14:27:37
        • modified2024-10-29 11:19:44
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • approved2
• $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