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    • Application(array)
      • id664
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      • trial_status_id5
      • abstract_of_study<div>\n <p>\n Environmental enteric dysfunction (EED) is an intestinal disorder common among people living in low-resource settings (LRS), which in children has been associated with increased risk of growth stunting, reduced cognitive development, and reduced oral vaccine responsiveness. An effective EED therapeutic would offer an opportunity to improve child growth and development in LRS. One promising intervention, enterade® (an amino acid–based oral rehydration solution [AA-ORS]), is a medical food product already sold in the United States. It consists of oral rehydration salts and a proprietary blend of amino acids designed to restore gut function, improve nutrient and electrolyte absorption, and improve barrier integrity. There is evidence that this AA-ORS reduces inflammation and promotes healing of damaged intestinal epithelium in murine models of intestinal damage (irradiated gut), and it may provide benefit to pediatric EED patients. Supplementation of amino acids may lessen or improve intestinal injury related to enteric illnesses commonly experienced in settings of poor hygiene and sanitation infrastructure. We will conduct a randomized, double-blinded, placebo-controlled pilot study in Kakamega County, Kenya, to assess the safety, feasible dosage, and acceptability/tolerability of the product in the target population (children aged 12–24 months) and their caregivers.</p>\n</div>\n<p>\n  </p>\n
      • study_title<h2 align=\"center\">\n Safety, Acceptability, and Feasibility of enterade® in children at risk for environmental enteric dysfunction in Kakamega County, Kenya</h2>\n
      • laymans_summary<div>\n <p>\n Environmental enteric dysfunction (EED) is an intestinal disorder common among people living in low-resource settings (LRS), which in children has been associated with increased risk of growth stunting, reduced cognitive development, and reduced oral vaccine responsiveness. An effective EED therapeutic would offer an opportunity to improve child growth and development in LRS. One promising intervention, enterade® (an amino acid–based oral rehydration solution [AA-ORS]), is a medical food product already sold in the United States. It consists of oral rehydration salts and a proprietary blend of amino acids designed to restore gut function, improve nutrient and electrolyte absorption, and improve barrier integrity. There is evidence that this AA-ORS reduces inflammation and promotes healing of damaged intestinal epithelium in murine models of intestinal damage (irradiated gut), and it may provide benefit to pediatric EED patients. Supplementation of amino acids may lessen or improve intestinal injury related to enteric illnesses commonly experienced in settings of poor hygiene and sanitation infrastructure. We will conduct a randomized, double-blinded, placebo-controlled pilot study in Kakamega County, Kenya, to assess the safety, feasible dosage, and acceptability/tolerability of the product in the target population (children aged 12–24 months) and their caregivers.</p>\n</div>\n<p>\n  </p>\n
      • short_titleSafety, Acceptability, and Feasibility of enterade® (SAFE)
      • protocol_noECCT/18/06/01
      • version_no1.5
      • date_of_protocol07-05-2018
      • study_drugenterade
      • disease_conditionEnvironmental enteric dysfunction
      • product_type_biologicals0
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameAmino Acid-based Oral Rehydration Solution (AA-ORS)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressMArndt@path.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_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_applicantJames Mukabi
      • declaration_date106-06-2018
      • declaration_principal_investigatorMichael Arndt (co-PI)
      • declaration_date206-06-2018
      • placebo_presentYes
      • study_objectives<div>\n <p>\n Primary Objective: To determine the safety of AA-ORS among children with mild to moderate stunting, administered as a daily dose over 2 weeks, ad libitum up to 237 ml in 3 hours.</p>\n <p>\n <em>Safety assessment in children will compare adverse event (AE) and serious adverse event (SAE) rates and changes to dietary and digestive habits between children receiving AA-ORS versus an inactive placebo solution containing no amino acids.</em></p>\n <p>\n Primary Objective: To determine the feasibility and well-tolerated dose of AA-ORS among children with mild to moderate growth stunting administered as a daily dose over 2 weeks, ad libitum up to 237 ml in 3 hours.</p>\n <p>\n <em>User preferences among children include average daily volume consumed over days, trends in volume consumed, and factors that influence children’s willingness and ability to ingest the product as intended.</em></p>\n <p>\n Secondary Objective: To determine the perceptions among caregivers on the use and acceptability of this product as a potential intervention for EED.</p>\n <p>\n <em>Acceptability by caregivers includes factors that influence their willingness to have the product used by their children and their perception of their child’s response to its consumption.</em></p>\n <p>\n Exploratory Objective: To determine the impact of AA-ORS on gut dysfunction, metabolism, gut and systemic inflammation, and micronutrient status.</p>\n <p>\n <em>Impact of AA-ORS on gut dysfunction, systemic inflammation, and micronutrient status</em><em> will be assessed by comparing non-invasive biomarker levels in blood samples collected following the intervention. These biomarkers will be assessed in both groups at baseline in order to have setting-specific descriptive data with which to power a future EED efficacy trial.</em></p>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n <u>Pediatric and caregiver pairs (must meet inclusion criteria for both categories):</u></p>\n<p>\n Child:</p>\n<ol>\n <li>\n Is between 12 and 24 months of age.</li>\n <li>\n LAZ between –1 and –3 SD.</li>\n <li>\n At least one week post routine immunization or vitamin A supplementation visit at the study site.</li>\n <li>\n Has a parent or legally acceptable representative willing and able to provide informed consent.</li>\n <li>\n No plans for travel outside of the community for the duration of the study.</li>\n</ol>\n<p>\n Caregiver of child:</p>\n<ol>\n <li>\n Is a parent or legally accepted representative of a child eligible for this study.</li>\n <li>\n Is 18 years of age or older.</li>\n <li>\n Has a working mobile phone.</li>\n <li>\n Is willing and able to provide informed consent.</li>\n <li>\n If illiterate—there is at least one literate adult living in the child’s household.</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n <u>Pediatric and caregiver pairs (must meet none of the exclusion criteria for either category):</u></p>\n<p>\n Child:</p>\n<p style=\"margin-left:.25in;\">\n 1.       Has any sign of acute illness, including but not limited to fever, cough, and diarrhea.</p>\n<p style=\"margin-left:.25in;\">\n 2.       Is wasted (weight for length z-score < –2 or mid-upper arm circumference [MUAC] < 12.4 cm) or has pitting edema.</p>\n<p style=\"margin-left:.25in;\">\n 3.       Is exclusively breastfed.</p>\n<p style=\"margin-left:.25in;\">\n 4.       Is seeking medical attention at the health facility other than for routine, preventative care (e.g., immunization visit, vitamin supplementation).</p>\n<p style=\"margin-left:.25in;\">\n 5.       Has suffered within the prior week from illnesses that might impact nutritional status (e.g., severe diarrhea or pneumonia; vomiting; persistent diarrhea; cleft lip or palate; blindness; tuberculosis; jaundice; renal or cardiac disease; cerebral palsy; known metabolic disorders; and chromosomal disorders, including trisomy 21).</p>\n<p style=\"margin-left:.25in;\">\n 6.       Medical history of chronic health condition (i.e., HIV, hepatitis B or C, end stage renal disease, severe liver disease—absence of a diagnosis is sufficient).</p>\n<p style=\"margin-left:.25in;\">\n 7.       Participating in any other clinical trials.</p>\n<p style=\"margin-left:.25in;\">\n 8.       Recent (prior 2 weeks) use of antibiotics or any other medical treatments (including ORT, but not including vaccines or vitamin/mineral supplementation).</p>\n<p style=\"margin-left:.25in;\">\n 9.       Cannot give the necessary biological (blood) sample.</p>\n<p>\n Caregiver:</p>\n<p>\n Reports diarrhea in the household in the prior 7 days.</p>\n
      • primary_end_points<p>\n <strong>Primary:</strong> Adverse events and serious adverse events through 28 days of follow-up, and changes to dietary and digestive habits through day 21 of follow-up.</p>\n<p>\n <strong>Primary:</strong> Average product volume consumed daily through 21 days of follow-up, time trends in average daily volume consumed, and factors that influence children’s willingness and ability to ingest the product as intended.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • 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_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyThis study will provide critical information about the safety of commercially available AA-ORS in this at-risk pediatric population and qualitative and quantitative information on the user-preferred product volume for this age group, palatability, and ease of administration.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <p>\n Kakamega CGH is a Level 5 Hospital that offers maternal services, comprehensive care center (CCC) services, maternal and child health unit, comprehensive emergency obstetric care, curative in-patient services, curative outpatient services, family planning, growth monitoring and promotion, HIV counselling and testing, rural health training centre / rural health demonstration centre, Tuberculosis services, laboratory services.</p>\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"547\">\n <tbody>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Consultants </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p>\n 19, two (2) of which are Pediatricians and two (2) are obstetrician/Gynecologists.</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n General Doctors/Registrars</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 43</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Pharmacists</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 7</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Pharmaceutical Technologists </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 6</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Medical Laboratory Technologists</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 25</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Dental Officers </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Clinical Officers </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 29</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Nutritionists </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 3</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Nursing Officers </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 261</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Public Health officers </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Health Promotion Officers </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Plaster Technologists </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Medical Social Worker </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Health Administrator </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:5px;\">\n <p>\n Orthopedic Technologists </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:5px;\">\n <p align=\"right\">\n 7</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Physiotherapists</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n                11</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Occupational Therapists</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 6</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Dental Technologists/COHO </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 3</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Records Officers </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 11</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Radiographers                </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 11</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Medical Engineers           </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 9</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Secretaries                       </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 2</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Clerical Officers               </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Drivers                              </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 5</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Telephone Operators    </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 2</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Artisans                             </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Mortuary Attendants     </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 6</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Cooks                                </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 2</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n ICT                                     </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 2</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Support Staff                  </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 13</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n Casuals                            </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 99</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:236px;height:20px;\">\n <p>\n TOTAL  </p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:311px;height:20px;\">\n <p align=\"right\">\n 586</p>\n </td>\n </tr>\n </tbody>\n </table>\n <p>\n  </p>\n <p>\n <strong>Number of Beds:</strong> 449</p>\n <p>\n  </p>\n <p>\n <strong>Number of Cots:</strong> 79</p>\n <p>\n  </p>\n <p>\n Research study staff:</p>\n <p style=\"margin-left:30.5pt;\">\n <strong>Dr. James Mukabi, MD<em>. </em></strong>Principal Investigator.</p>\n <p style=\"margin-left:30.5pt;\">\n <strong>Alfred Ochola, MPH.</strong> Project coordinator.</p>\n <p style=\"margin-left:30.3pt;\">\n <strong>Dorothy Brown, Kenya Registered Nurse. </strong>Study nurse.</p>\n <p style=\"margin-left:30.3pt;\">\n <strong>Dr. Nick </strong><strong>Aduro</strong><strong> Kidaha, MBChB, MMed (Paeds). </strong>Study pediatrician.</p>\n <p style=\"margin-left:30.3pt;\">\n <strong>Research assistant(s), to be determined. </strong></p>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The study will be conducted in Kakamega County in Western Kenya. Kakamega county was selected as containing both rural and urban settings and is suitable for this research due to the high prevalence of malnutrition, and PATH Kenya’s established relationships with health facilities in the area. In former Nyanza province, the stunting (LAZ<-2) prevalence in children under 5 years ranges from 2.5% in Migori County to 5.14% in Kisumu County. In neighboring Western province, where Kakamega is located, the prevalence is thought to be much higher. PATH has been involved in the establishment of the APHIA<em>plus </em>program in western Kenya. APHIA<em>plus</em> promotes HIV testing and improved access to ORS for children experiencing diarrhea through ORS corners in several hundred health facilities in the region. Participants will be recruited from Kakamega County General Hospital (CGH). This facility draws from a peri-urban catchment area, has been participating in APHIA<em>plus</em> programming, and has set up an ORS corner for treatment of pediatric diarrhea. Therefore, health care providers in the facility are quite familiar with the use of ORS.</p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p align=\"left\">\n None.</p>\n
      • other_details_regulatory_approved<p>\n None.</p>\n
      • other_details_regulatory_rejected<p>\n None.</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</p>\n
      • estimated_duration4 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo solution
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKakamega County General Hospital (CGH)
      • single_site_physical_addressP.O. Box 15-G.P.O.-50100 Kakamega, Kenya
      • single_site_contact_personVictor Zimbulu, Medical Superintendent
      • single_site_telephone0702930346
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site66
      • total_participants_worldwide66
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren between the ages of 12 and 24 months
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJames
      • investigator1_middle_name
      • investigator1_family_nameMukabi
      • investigator1_qualificationMBChB, MPH
      • investigator1_professional_addressPATH Kakamega- Kenafya Building, Okwemba Road next to Kenya Medical Training College Kakamega 50100
      • investigator1_telephone+254722565432
      • investigator1_emailjmukabi@path.org
      • organisations_transferred_Yes
      • number_participants66
      • notification<p>\n Dear PPB --</p>\n<p>\n Attached please find PATH’s request for closure of the Safety, Acceptability, and Feasibility of Enterade® (SAFE) study in Children at Risk for Environmental Enteric Dysfunction in Kakamega County, Kenya.</p>\n<p>\n The request includes the following documents:</p>\n<ul>\n <li>\n Cover letter</li>\n <li>\n SAFE Executive Summary Final Report</li>\n <li>\n DSMB Final Meeting Minutes</li>\n</ul>\n<p>\n  </p>\n<p>\n We will be submitting the Clinical Study Report to PPB no later than the July 31, 2020 (180 days following study closure).</p>\n<p>\n  </p>\n<p>\n Kindly let us know if you need additional information.</p>\n<p>\n  </p>\n<p>\n Thank you for the support during the study.</p>\n<div>\n  </div>\n
      • approval_date02-10-2018
      • submitted1
      • deleted0
      • deleted_date2018-04-09 14:53:11
      • deactivated0
      • date_submitted28-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n Environmental enteric dysfunction (EED) is an intestinal disorder common among people living in lowresource settings (LRS), which in children has been associated with increased risk of growth stunting, reduced cognitive development, and reduced oral vaccine responsiveness. Supplementation of amino acids may lessen or improve intestinal injury related to enteric illnesses commonly experienced in settings of poor hygiene and sanitation infrastructure.</p>\n<p>\n We conducted a randomized, double-blinded, placebo-controlled pilot study in Kakamega County, Kenya, to assess the safety, feasible dosage, and caregiver acceptability of enterade®, an amino acid-based oral rehydration solution (AA-ORS), in the target population of children at risk for EED. Children were randomized to to receive AA-ORS or placebo solution (given ad libitum for 3 hours, up to 237 ml) for 14 days, and compare the rate of adverse events (AEs) in the two groups through 21 days of follow up.</p>\n<p>\n enterade® (an amino acid–based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts and a blend of amino acids that drive the uptake of water and electrolytes. The blend of amino acids appears to reduce intestinal damage and promote healing of the intestinal epithelium in irradiated mouse models commonly used to simulate gut damage encountered in inflammatory bowel diseases. This AA-ORS contains water, a proprietary blend of amino acids (L-Valine, L-Aspartic Acid, L-Serine, L-Threonine, and L-Tyrosine), sodium chloride, sodium citrate, potassium chloride, gum acacia, magnesium chloride, calcium chloride, and stevia leaf extract (sweetener).</p>\n<p>\n A total of 12 participants aged 12-24 months with length for age z-score between -1 and -3, from outpatient department at Kakamega County General Hospital in Kakamega, Kenya were enrolled before the study terminated on May 2, 2019. Several rounds of microbial testing on bottles stored at the study site in Kenya and from the manufacturer’s warehouse confirmed that some of the study product bottles were contaminated with potentially pathogenic microorganisms: <em>Burkholderia cepacia, Cryptococcus uniguttulatus,</em> <em>Exophiala dermatitidis, Exophiala heteromorpha</em>, <em>Capronia munkii, Penicillium roqueforti</em>, and <em>Eurotium herbariorum</em> (a.k.a. <em>Aspergillus glaucus</em> OR <em>Eurotium rubrum</em> (a.k.a. <em>A. rubrum</em>).</p>\n<p>\n Following study termination, an additional weekly safety follow-up of all participants that were enrolled in the study for an additional 6 weeks received ethical approvals as a change to research procedures, but not as an amendment to the protocol. In order to inform SAFE study participants about the study product microbial testing findings and proposed safety follow-up, a letter was sent to each enrolled child-caregiver pair. This letter summarized the current study status; known risks of potential exposure to microbial contaminants; what to do in case of any observed adverse event(s), question, or concern; and details of the purposed 6-week safety follow-up. Subsequently, a consent form addendum was signed by caregivers to authorize the additional safety follow-up procedures.</p>\n<p>\n All 12 participants that were enrolled in the study between February 26, 2019 and March 20, 2019 (the date of study suspension) were contacted and consented to the 6-week safety follow-up. The informed consent form allowed for travel reimbursement on an as-needed basis. The additional weekly safety follow-up for all 12 participants that were enrolled in the SAFE study were conducted between November 20, 2019 and January 16, 2020. All research participants completed the procedures done as part of the additional safety follow-up and/or monitoring.</p>\n<p>\n Any adverse events (AEs) that were noticed by participants, however minor, from the time the study was terminated to date were recorded (see Table 1 below). Five out of the 12 participants reported at least one AE following the study. All safety reports of acute illness were reported recovering/resolving or recovered/resolved. Only PT021 experienced two AEs that were ongoing at the end of the study and thus has no end date recorded.</p>\n<p>\n  </p>\n<p>\n Table 1. Details on adverse events reported by participant during additional safety assessment.</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:111px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:69px;\">\n <p>\n <strong>Severity</strong></p>\n </td>\n <td style=\"width:66px;\">\n <p>\n <strong>Start date</strong></p>\n </td>\n <td style=\"width:67px;\">\n <p>\n <strong>End date</strong></p>\n </td>\n <td style=\"width:186px;\">\n <p>\n <strong>Medical action</strong></p>\n </td>\n <td style=\"width:79px;\">\n <p>\n <strong>Resolving/ resolved</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n <strong>PT005</strong></p>\n </td>\n <td style=\"width:69px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:66px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:67px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:186px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:79px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n      Diarrhea</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/17/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 11/22/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n ORS and amoxicillin</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n      Fever</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/17/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 11/19/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n Artemether lumefantrine and paracetamol</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n <strong>PT006</strong></p>\n </td>\n <td style=\"width:69px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:66px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:67px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:186px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Cough</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/21/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 11/24/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n Amoxicillin, panadol, piriton</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Runny nose</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/21/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 11/25/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n None</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n <strong>PT016</strong></p>\n </td>\n <td style=\"width:69px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:66px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:67px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:186px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Cough</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/24/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 11/27/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n Septrin, piriton and panadol</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n <strong>PT021    </strong></p>\n </td>\n <td style=\"width:69px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:66px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:67px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:186px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Cough</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/16/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n Ongoing</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n Baby on co-trimoxazole; mother on care</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Night sweats</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 11/16/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n Ongoing</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n None</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n <strong>PT049</strong></p>\n </td>\n <td style=\"width:69px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:66px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:67px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:186px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Diarrhea</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Moderate</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 12/11/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 12/14/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n ORS, piriton, and amoxicillin</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Fever</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Moderate</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 12/11/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 12/12/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n Paracetamol</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:111px;\">\n <p>\n       Vomiting</p>\n </td>\n <td style=\"width:69px;\">\n <p>\n Mild</p>\n </td>\n <td style=\"width:66px;\">\n <p>\n 12/11/19</p>\n </td>\n <td style=\"width:67px;\">\n <p>\n 12/12/19</p>\n </td>\n <td style=\"width:186px;\">\n <p>\n None</p>\n </td>\n <td style=\"width:79px;\">\n <p align=\"center\">\n Y</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n The study closeout visit was conducted once the last participant completed study participation in the additional safety follow-up. The three-day closeout visit was conducted between January 28-30, 2020 by the Independent Study Monitor (ISM). The final DSMB meeting to review additional safety assessment findings and study closeout was held on February 11, 2020.</p>\n<p>\n All study product that were shipped from the study site to the manufacturer and Nelson Laboratories for microbial testing have been discarded. The remaining study product at the study site is accounted for and awaiting destruction in the presence of the Kenyan Pharmacy and Poisons Board (PPB) regulatory representative on February 25-26, 2020.</p>\n<p>\n The completion of biomarker testing of blood samples by staff at the Kenya Medical Research Institute (KEMRI) laboratory in Kilifi is underway to measure enteric dysfunction, systemic inflammation, and micronutrient deficiency in this small pediatric sample. These exploratory analyses are on a small sample size that lacks adequate power for statistical comparisons of the EED outcomes (non-invasive biomarkers); however, the expected results from the exploratory biomarker testing could be useful for understanding EED in this locality and special population and informing study design considerations for future research on AA-ORS and similar EED interventions in LRS. The Environmental Enteric Dysfunction Assessment Tool (MEEDAT) kits to complete the exploratory laboratory assays will measure the average plasma/serum concentrations of gut dysfunction, systemic inflammation, and micronutrient biomarkers will be tested on blood samples that were collected at baseline and day 22 of follow-up. All blood samples following completion of the exploratory laboratory assays by KEMRI will be destroyed.</p>\n
      • implication_results(null)
      • quantity_imported1702
      • quantity_dispensed149
      • quantity_destroyed950
      • quantity_exported471
      • balance_site0
      • final_date0000-00-00
      • modified2020-03-28 00:27:53
      • created2018-03-29 00:53:21
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        • id418
        • application_id664
        • given_nameMichael
        • middle_nameBenjamin
        • family_nameArndt
        • qualificationPhD
        • professional_address2201 Westlake Ave. Suite 200 Seattle, WA 98121 United States
        • telephone206-285-3500
        • emailmarndt@path.org
        • created2018-03-29 00:56:16
        • modified2020-03-28 00:19:43
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        • given_nameJames
        • middle_name
        • family_nameMukabi
        • qualificationMBChB, MPH
        • professional_addressPATH Kakamega- Kenafya Building, Okwemba Road next to Kenya Medical Training College Kakamega 50100
        • telephone+254722565432
        • emailjmukabi@path.org
        • created2018-04-03 04:43:20
        • modified2020-03-28 00:19:43
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        • contact_personMichael Arndt
        • address2201 Westlake Ave. Suite 200
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        • cell_number+19254874527
        • email_addressmarndt@path.org
        • created2018-03-29 00:56:16
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  • 1(array)
    • Application(array)
      • id658
      • user_id73
      • trial_status_id7
      • abstract_of_study<div>\n A challenge to development of HIV-1 vaccines is to better understand the natural immune mechanisms for protection from HIV-1 infection. To this end, immunologists have increasingly appreciated the importance of regulatory T cells in peripheral blood that modulate the magnitude and characteristics of the host</div>\n<div>\n inflammatory response including against infectious diseases. We have also recently identified specific host genetic variants in the genes CD101 and UBE2V1 that appear to strongly predispose to HIV-1 infection risk and may act through regulatory T cells and other immunologic pathways. Most studies of individuals who are repeatedly HIV-1 exposed but remain seronegative (HESN) have focused on immunological correlates in peripheral blood rather than mucosal immune responses. However, with genital mucosal tissues being the portal of entry for heterosexually transmitted HIV-1 infection, it is critical that we understand the role of immunological responses to HIV-1 that occur in the genital mucosa. A valuable model to carry out such studies is offered by HESN, particularly in the context of heterosexual sex with a stable HIV-1 infected partner e.g., HIV-1 serodiscordant couples (SDC). In order to understand how exposure to HIV-1 may modulate these immune pathways, HIV-1 serodiscordant couples should be compared to heterosexual partners in concordant HIV-1 negative couples (CNC) where neither partner has HIV-1. Here we propose to address this important knowledge gap by enrolling high-risk HESN with defined heterosexual HIV-1 exposures in the context of serodiscordant partnerships compared to unexposed concordant seronegative controls. We will prospectively obtain mucosal and peripheral blood samples for a detailed analysis of longitudinal immune responses, while also collecting samples for genetic characterization to understand how variants in CD101 and UBE2V1 may modulate host mucosal responses and HIV-1 infection risk.</div>\n<div>\n  </div>\n<div>\n <strong>Design:</strong> Single study site, prospective, observational cohort.</div>\n<div>\n  </div>\n<div>\n <strong>Population</strong>: African heterosexual HIV-serodiscordant (SDC) and HIV-1 concordant negative couples (CNC) will be recruited for this study. The exclusion criteria will be current use of ART by HIV-1 infected partners, or PrEP by HIV-1 uninfected partners at the time of screening or prior to enrollment. Inclusion criteria applied to all partners includes age≥18 years, willingness to engage in voluntary couples HIV-1 counseling and testing, to disclose these testing results to their enrolled partner, and to provide samples requested. Among SDC the HIV-1 uninfected partners may be either male or female.</div>\n<div>\n  </div>\n<div>\n <strong>Study Size: </strong>The study will enroll both partners in 500 heterosexual Kenyan couples:</div>\n<div>\n  </div>\n<div>\n • <strong>300 </strong>HIV-1 serodiscordant couples (200 with male, and 100 with female HIV-1 infected partners) and</div>\n<div>\n • <strong>200</strong> HIV-1 concordant seronegative couples (400 HIV-1 negative partners).</div>\n<div>\n  </div>\n<div>\n  </div>\n
      • study_title<p>\n Immunogenetic Modulators of Mucosal Protection from HIV-1: The Kinga Study</p>\n
      • laymans_summary<div>\n A challenge to development of HIV-1 vaccines is to better understand the natural immune mechanisms for protection from HIV-1 infection. To this end, immunologists have increasingly appreciated the importance of regulatory T cells in peripheral blood that modulate the magnitude and characteristics of the host</div>\n<div>\n inflammatory response including against infectious diseases. We have also recently identified specific host genetic variants in the genes CD101 and UBE2V1 that appear to strongly predispose to HIV-1 infection risk and may act through regulatory T cells and other immunologic pathways.</div>\n
      • short_titleKINGA Study
      • protocol_noECCT/18/05/02
      • version_no2.3
      • date_of_protocol28-02-2018
      • study_drugTruvada - Immunogenetic Modulators (KINGA Study)
      • disease_conditionHuman Immunodeficiency Virus
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameTenofovir Disoproxil Fumarate 300mg / Emtricitabine 200mg (TDF/FTC)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRwamba@csrtkenya.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
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      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantPeter Mogere
      • declaration_date103-05-2018
      • declaration_principal_investigatorDr. Nelly Mugo
      • declaration_date203-05-2018
      • placebo_presentNo
      • study_objectives<p>\n  <strong>Primary Objective:</strong></p>\n<ul>\n <li>\n To identify mucosal immunoregulatory mechanisms in host response to natural heterosexual exposure to HIV-1.</li>\n <li>\n To determine how high priority variants in <em>CD101 </em>and <em>UBE2V1</em> modify host mucosal responses to HIV-1 exposure and infection.</li>\n</ul>\n<p>\n <strong>Secondary Objective:</strong></p>\n<p>\n 1) <u>Identify factors influencing immunoregulatory mechanisms in host response to HIV-1</u></p>\n<ul>\n <li>\n To evaluate the impact on host immunoregulatory responses from variation in cofactors including but not limited to</li>\n</ul>\n<ul style=\"list-style-type:circle;\">\n <li>\n sexually transmitted infections and the host microbiome,</li>\n <li>\n HIV-1 exposure as defined by the frequency of sexual activity and the HIV-1 viral load in the HIV-1 infected partner, and</li>\n <li>\n HIV-1 prevention measures including antiretroviral PrEP provided to the HESN partner, or ART provided to the HIV-1 infected partner.</li>\n <li>\n Characteristics of sexual exposures (frequency, type and duration of sex acts)</li>\n</ul>\n<ul>\n <li>\n To assess the effect of biological factors such as host genetic factors, microbiome and virome constituents and viral genetic factors on these immunoregulatory responses.</li>\n <li>\n To determine how these immunogenetic responses may alter HIV-1 disease progression</li>\n</ul>\n<p style=\"margin-left:.25in;\">\n  </p>\n<p style=\"margin-left:13.5pt;\">\n 2) <u>To evaluate how these immunogenetic regulatory mechanisms influence other infectious and immunological outcomes:</u></p>\n<ul>\n <li>\n To assess the role immunoregulatory mechanisms on host response to other infections (e.g., sexually transmitted infections and bacterial vaginosis),</li>\n <li>\n To define the role of these immunogenetic regulatory mechanisms in other acute and chronic manifestations of inflammation.</li>\n</ul>\n<p>\n  </p>\n<p>\n 3) <u>Evaluate the effect of PrEP on early HIV-1 disease</u></p>\n<ul>\n <li>\n Among initially HIV-1 uninfected individuals in the study who seroconvert to HIV-1, to assess the level of genital tract inflammation present prior to HIV-1 infection.</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong>Tertiary Objectives</strong></p>\n<ul>\n <li>\n To utilize archived samples from this study for evaluation of immunogenetic and virologic determinants on inflammatory disorders, and HIV-1 and sexually transmitted infection (STI) acquisition, transmission and disease progression including viral phenotype and genotype, HIV-1 co-receptor usage, innate and adaptive immune polymorphisms, human genomic, microbiome and virome constituents and other biological factors.  </li>\n</ul>\n
      • principal_inclusion_criteria<div>\n The partner (HIV-1 uninfected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:</div>\n<ul>\n <li>\n Age ≥18 and ≤65 and able to provide independent informed consent for research per local regulations and guidelines</li>\n <li>\n Able and willing to provide written informed consent to be screened for and to take part in the study</li>\n <li>\n Part of a heterosexual couple in which either one or both partners meet the study eligibility criteria for partner (HIV-1 uninfected) participants.</li>\n</ul>\n<div>\n Potential index (HIV-1 infected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:</div>\n<div>\n  </div>\n<ul>\n <li>\n Of legal age to provide independent informed consent for research per local regulations and guidelines.</li>\n <li>\n Able and willing to provide written informed consent to be screened for and to take part in the study.</li>\n <li>\n Part of a heterosexual couple in which one partner meets the study eligibility criteria for index (HIV-1 infected) participants and the other partner meets the study eligibility criteria for partner (HIV-1 uninfected) participants, including the following criteria for the couple:</li>\n <li>\n Partners who are sexually active (defined as having had vaginal intercourse with the enrolled HIV-1 uninfected partner participant at least 6 times in the last three months)</li>\n <li>\n Partners plan to remain in the relationship for at least 6 months</li>\n <li>\n Current or previous use of antiretroviral therapy with unsuppressed HIV-1 viral load</li>\n <li>\n HIV-1 infected based on positive EIA and, when available, detectable viral load.</li>\n <li>\n No history of any clinical AIDS-defining diagnoses.</li>\n <li>\n Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures.</li>\n</ul>\n<div>\n  </div>\n
      • principal_exclusion_criteria<div>\n Potential partner (HIV-1 uninfected) participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:</div>\n<div>\n  </div>\n<ul>\n <li>\n Abnormal serum creatinine (based on sub-Saharan African normal values)</li>\n <li>\n Active and serious infections, including active tuberculosis infection or osteomyelitis and all infections requiring parenteral antibiotic therapy; active clinically significant medical problems including cardiac disease (e.g., symptoms of ischemia, congestive heart failure or arrhythmia), pulmonary disease (steroid dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication; and previously diagnosed malignancy expected to require further treatment.</li>\n</ul>\n<div>\n <ul>\n <li>\n Receiving ongoing therapy with any of the following at the time of enrollment: interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, metformin, aminoglycoside antibiotics, amphotericin B, cidofovir, systemic chemotherapeutic agents, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents</li>\n <li>\n At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data)</li>\n <li>\n Pregnant at the time of screening.</li>\n </ul>\n <div>\n Potential index (HIV-1 infected) participants who meet any of the following criteria (by selfreport, unless otherwise indicated) will be excluded from the study:</div>\n <div>\n  </div>\n <ul>\n <li>\n Current or previous use of antiretroviral therapy with suppressed HIV-1 viral load</li>\n <li>\n Currently enrolled in another HIV-1 treatment trial</li>\n <li>\n At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data; or otherwise interfere with achieving the study objectives.</li>\n <li>\n Pregnant at the time of screening</li>\n </ul>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n This is a prospective observational study that intends to understand the role of immunological responses to HIV-1 that occur in the genital mucosa. This is important since genital mucosal tissues presents the portal of entry for heterosexually transmitted HIV-1 infection. There being HIV serodiscordant couples participating in the study, HIV seroconversion will be an endpoint.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • 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_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Partners in Health & Research Development (Formerly Partners in Prevention), has 38 full time clinical trial staff (including physicians, nurses, counsellors, pharmacist, pharmaceutical technologists, clinical officers, social scientists, administrative staff ).</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Principal Investigator: Dr. Nelly R. Mugo  MBCHB,MMED,MPH</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Co-Investigator: Dr. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">The greatest burden of the HIV-1 epidemic lies in sub-Saharan Africa, where a substantial proportion of infections occur in long-term HIV-1 serodiscordant partnerships, i.e. where one partner is HIV-1 infected and the other uninfected. </span>A challenge to development of HIV-1 vaccines is to better understand the natural immune mechanisms for protection from HIV-1 infection. To this end, immunologists have increasingly appreciated the importance of regulatory T cells in peripheral blood that modulate the magnitude and characteristics of the host inflammatory response including against infectious diseases. We have also recently identified specific host genetic variants in the genes <em>CD101 </em>and <em>UBE2V1 </em>that appear to strongly predispose to HIV-1 infection risk and may act through regulatory T cells and other immunologic pathways. Most of the sample analyses leading to the conception of this concept was conducted on speciemen samples collected in previous studies conducted in Kenya. As it is with other East African countries, Kenya has the highest number of individuals in HIV serodiscordant relationships. Kinga study seeks to explore the immunogetic responses that will in the end might offer an understanding of how to come up with an effective vaccine against HIV.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU - 13th March 2018</p>\n<p>\n UW IRB          -  18th May 2017</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-CCR - Partners in Health Research & Development (PHRD) Thika Site.
      • single_site_physical_addressPartners in Prevention House, Thika Section 9, OAU Road
      • single_site_contact_personDr. Kenneth Ngure
      • single_site_telephone067 2222561/0725641110
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site500 heterosexual Kenyan couples
      • total_participants_worldwide500 heterosexual Kenyan couples
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJairam
      • investigator1_middle_nameRao
      • investigator1_family_nameLingappa
      • investigator1_qualificationMD, PHD
      • investigator1_professional_addressInternational Clinical Research Center Department of Global Health, University of Washington Ninth and Jefferson Building 908 Jefferson, 12th floor, Room 1231 Seattle, WA 98104
      • investigator1_telephone+1-206-520-3822
      • investigator1_emaillingappa@uw.edu
      • organisations_transferred_Yes
      • number_participants500 heterosexual Kenyan couples
      • notification
      • approval_date26-07-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted31-03-2020
      • 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)
      • modified2021-07-06 12:56:35
      • created2018-03-22 13:35:47
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id416
        • application_id658
        • given_nameNelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBChB, MMeD, MPH
        • professional_address19865 - 00202
        • telephone067 2222561/0723914057
        • emailrwamba@csrtkenya.org
        • created2018-03-22 13:37:48
        • modified2020-03-31 18:06:00
    • SiteDetail(array)
      • 0(array)
        • id534
        • application_id658
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2018-03-22 13:37:48
        • modified2020-03-31 18:06:00
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id332
        • application_id658
        • sponsorFred Hutchinson Cancer Research Center, University of Washington
        • sponsor_typeOthers
        • contact_personDr. Nelly R. Mugo
        • address19865 - 00202
        • telephone_number067 2222561
        • fax_number
        • cell_number0723914057
        • email_addressrwamba@csrtkenya.org
        • created2018-03-22 13:37:48
        • modified2020-03-31 18:06:00
  • 2(array)
    • Application(array)
      • id655
      • user_id72
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Background:</strong></p>\n<p>\n EIMC is technically simpler, safer, and less expensive compared to VMMC performed in older children or adults. However, scarcity of trained providers and resources in sub-Saharan Africa are a barrier to EIMC services. Device-assisted VMMC could simplify the procedure, enable safe task-shifting, thus increasing the availability of this service.</p>\n<p>\n  </p>\n<p>\n <strong>Objective:</strong></p>\n<p>\n To evaluate the safety, effectiveness and acceptability of the ShangRing device for EIMC.</p>\n<p>\n  </p>\n<p>\n <strong>Study design:</strong></p>\n<p>\n The study will be in two phases. In the pilot phase, 460 eligible infants will be randomised 1:1 to receive either ShangRing or Mogen clamp circumcision. Follow up will occur every seven days afterward until 42 post circumcision or until the circumcision wound is completely healed. We will assess the circumcision time, pain, adverse event (AEs), healing course, and parent and provider preferences. In the second field phase, 600 eligible infants will undergo ShangRing EIMC performed by non-physicians in routine settings. Outcomes will be similar to the first phase.</p>\n<p>\n  </p>\n<p>\n <strong>Expected results</strong>:</p>\n<p>\n Comparative safety of the two devices would be determined by the differences in the AE rates, pain experienced, parent/provider preferences. Safety and effectiveness of the ShangRing in routine clinical settings by non-physicians will be evaluated by the AE rates and provider preferences.</p>\n<p>\n  </p>\n<p>\n <strong>Significance of the results:</strong></p>\n<p>\n This trial will determine whether the ShangRing is a safe and effective alternative for EIMC. Positive outcomes from this project could further facilitate scale-up of VMMC services in Sub-Saharan Africa. If the ShangRing is shown to be safe, effective and acceptable for EIMC, it will be the only VMMC device that can be used in males of all ages, from neonates to adults. A single device usable for all ages has substantial potential for simplification of service delivery, supply chain management, training and supervision, and educational materials. When complemented with strategies to ensure effective antiretroviral therapy for those with HIV infection, VMMC has been shown to be a cost-effective approach to move toward an AIDS-free generation. Use of the ShangRing in these efforts could help to achieve this goal.</p>\n<p>\n  </p>\n
      • study_title<p align=\"center\">\n <strong>Evaluation of the ShangRing vs. Mogen Clamp for Early Infant Male Circumcision in sub-Saharan Africa</strong></p>\n<p>\n  </p>\n
      • laymans_summary<div>\n This main aim of this trial is to compare the safety and acceptability of the ShangRing, a new device used to carry out male circumcision, vs. the Mogen clamp, another device that is approved and widely used to conduct male circumcision in children 0-60 days of age. </div>\n<div>\n This study shall be carried out in Kenya, Uganda and Tanzania. </div>\n<div>\n We will assess and compare adverse events, pain, wound healing and parent satisfaction. We will furthermore compare the length of time needed to carry out a circumcision using either device and the preferences of the clinicians who will use these devices. </div>\n<div>\n We would also like to know how feasible leaving the ShangRing device to fall off on its own is instead of needing the children to come back again to the clinic to have the device removed.</div>\n<div>\n Finally, given the concern around the bacteria that live on the surface of the penis, and how these may lead to Tetanus infection, we will also investigate this aspect on the children undergoing circumcision. This specific aim will be designed to comply with the comparative trial component of the WHO framework for such research on medical devices.</div>\n
      • short_titleShangRing vs. Mogen Clamp for EIMC
      • protocol_noECCT/18/04/03
      • version_no5
      • date_of_protocol20-01-2018
      • study_drugN/A
      • disease_conditionN/A
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameShangRing
      • comparatorYes
      • comparator_nameMogen clamp
      • comparator_registeredyes
      • comparator_countriesKenya, Uganda, Tanzania
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressqawori@engenderhealth.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_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_pi0
      • 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_applicantQuentin Awori qawori@popcouncil.org
      • declaration_date101-06-2018
      • declaration_principal_investigatorNational Principal Investigator
      • declaration_date201-06-2018
      • placebo_presentNo
      • study_objectives<div>\n <u><strong>Phase 1</strong></u></div>\n<div>\n  </div>\n<div>\n Primary Objective</div>\n<div>\n Evaluate the safety and acceptability of the no-flip ShangRing technique vs. Mogen</div>\n<div>\n clamp for EIMC in infants up to 60 days old</div>\n<div>\n  </div>\n<div>\n <div>\n Secondary Objectives</div>\n <div>\n ï‚· Assess ease of use of the ShangRing for EIMC</div>\n <div>\n ï‚· Evaluate satisfaction of ShangRing EIMC among parents of study participants</div>\n <div>\n ï‚· Evaluate satisfaction of using the ShangRing for EIMC among VMMC providers</div>\n <div>\n ï‚· Determine the occurrence and safety of spontaneous detachment</div>\n <div>\n ï‚· Determine the penile microbiome during the healing course in infants</div>\n <div>\n  </div>\n <div>\n <u><strong>Phase 2</strong></u></div>\n <div>\n  </div>\n <div>\n <div>\n Primary Objective</div>\n <div>\n Evaluate the use of ShangRing EIMC in a non-comparative field study in settings of</div>\n <div>\n intended use, if results from Phase I demonstrate reasonable safety and effectiveness of</div>\n <div>\n the ShangRing.</div>\n <div>\n  </div>\n <div>\n <div>\n Secondary Objectives</div>\n <div>\n ï‚· Assess ease of use of the ShangRing for EIMC</div>\n <div>\n ï‚· Evaluate satisfaction of ShangRing EIMC among parents of study participants</div>\n <div>\n ï‚· Evaluate satisfaction of using the ShangRing for EIMC among VMMC providers</div>\n <div>\n ï‚· Determine the occurrence and safety of spontaneous detachment</div>\n <div>\n ï‚· Assess the cost impact of EIMC using ShangRing vs. Mogen Clamp</div>\n <div>\n ï‚· Assess whether device-driven EIMC can be safely and effectively integrated into</div>\n <div>\n maternal and child health (MCH) services as a method to promote demand creation.</div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n All participants enrolled in this research study must meet the following inclusion criteria: </div>\n<div>\n ï‚·  male, age 1 to 60 days old,</div>\n<div>\n ï‚·  normal birth weight more than or equal to 2.5 Kg,</div>\n<div>\n ï‚·  gestational age more than or equal to 37 weeks,</div>\n<div>\n ï‚·  no illness requiring medical treatment,</div>\n<div>\n ï‚·  no penile abnormality requiring surgical repair (e.g. hypospadias),</div>\n<div>\n ï‚·  no family history of bleeding disorders.</div>\n<div>\n <div>\n ï‚·  parent or legally acceptable representative is 18 years of age or older</div>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div>\n A client will be excluded from participation in this research study if he has any of the </div>\n<div>\n following exclusion criteria: </div>\n<div>\n ï‚·  Congenital abnormality of the genitalia</div>\n<div>\n ï‚·  Any known haematological disorders, jaundice, yellow sclera or purpuric skin lesions</div>\n<div>\n ï‚·  Lack of parental consent</div>\n<div>\n ï‚·  Is currently participating in another biomedical research study</div>\n
      • primary_end_points<p>\n The study has two phases with different primary end points:</p>\n<p>\n Phase 1:</p>\n<p>\n The primary end point is the rate of adverse events between the two treatment groups i.e. ShangRing vs Mogen Clamp</p>\n<p>\n  </p>\n<p>\n Phase 2:</p>\n<div>\n The primary endpoint is the rate of adverse events when using the ShangRing in routine </div>\n<div>\n clinical settings by non-physician clinicians</div>\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_other1
      • trial_other_specifyUse of circumcision device in boys 0-60 days of age. Each of the device has been used in humans i.e. ShangRing in men and boys 10 years old and above, and Mogen clamp boy 0-60 days of age.
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u><strong>Homa Bay - Homa Bay TRH</strong></u></p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Staff at site who will conduct the research</strong></p>\n<ul font-size:=\"\" line-height:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Local PI : Jairus Oketch</li>\n <li style=\"line-height: 20px;\">\n 2 nurses - KRCHN\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Patrick Otiende</li>\n <li style=\"line-height: 20px;\">\n Nixon Nyangweso</li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n 1 Research Assistant\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Dan Ouma </li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n 1 Lead social mobiliser\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Nereah Obura</li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n Support staff (1)</li>\n</ul>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Site & Facility building</strong></p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Homa bay distirct hospital - VMMC Theatre</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <b><u>Kismu - Jaramogo Oginga Odinga TRH</u></b></p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Staff at site who will conduct the research</strong></p>\n<ul font-size:=\"\" line-height:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Local Site PI\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Godfrey Owino - BSc Health Ecomics, DCM</li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n 2 nurses - KRCHN\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Maureen Ongoro - KRCHN</li>\n <li style=\"line-height: 20px;\">\n Rachel Anyango - DCM</li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n 1 Research Assistant\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n To be named</li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n 1 Lead social mobiliser\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Dolrosa Anyango</li>\n </ul>\n </li>\n <li style=\"line-height: 20px;\">\n Support staff (1)\n <ul>\n <li style=\"line-height: 20px;\">\n Francis Kizito</li>\n </ul>\n </li>\n</ul>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Site & Facility building</strong></p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  - EIMC theatre (Maternity wing)</p>\n
      • other_details_explanation<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Kenya was the first country where research on the ShangRing as a device for VMMC was conducted (2009). Since then a lot of advancement into the use of the device has be gained plus inroads with the ministry of health (VMMC) and various stake holders.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n As this study is aimed at further improving the use of the device, Kenya is most suited to provide this environment of advanced research of this kind. Additionally, it is well placed to conduct the research and the comparator device, i.e. the Mogen clamp is in use in public health system.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n We suffice to say that Kenya is one of the three contries in the region, (includng Uganda and Tanzania) in which the study is being hosted.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Weill Cornel Medical College</p>\n<p>\n Kenya Medical and Research institute</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration2 years
      • 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_comparatorMogen Clamp device
      • 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_states3
      • number_of_sites2
      • multi_country_listKenya, Uganda, Tanzania
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrollment; two principal sites\nminimum per site : 0\nmaximum per site : 1060
      • total_participants_worldwide3180
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female0
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyInfants 0-42 days of age
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameQuentin
      • investigator1_middle_name
      • investigator1_family_nameAwori
      • investigator1_qualificationMBChB
      • investigator1_professional_addressAvenue Five, Rose Avenue, Hurlingham, Nairobi
      • investigator1_telephone+254722913616
      • investigator1_emailqawori@popcouncil.org
      • organisations_transferred_Yes
      • number_participants1060
      • notification
      • approval_date10-12-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-02-2020
      • 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)
      • modified2021-04-30 18:05:02
      • created2018-03-07 15:35:45
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id414
        • application_id655
        • given_nameRichard
        • middle_name
        • family_nameLee
        • qualificationMD, MBA (University of Pennsylvania), Fellow (Weill Cornell Medical College)
        • professional_address 425 E. 61st St., 12th Fl, NY, NY 10065.
        • telephone+1 646-962-4811
        • emailril9010@med.cornell.edu
        • created2018-03-07 16:27:37
        • modified2020-02-03 10:55:38
      • 1(array)
        • id415
        • application_id655
        • given_nameMark
        • middle_name
        • family_nameBarone
        • qualificationDVM(University of Colorado)
        • professional_addressPopulation Council 1230 York Avenue New York, NY 10065 USA
        • telephone+1 212-561-8084
        • emailmbarone@popcouncil.org
        • created2018-03-08 11:56:37
        • modified2020-02-03 10:55:38
    • SiteDetail(array)
      • 0(array)
        • id532
        • application_id655
        • county_id43
        • site_nameHoma Bay Teaching and Referral Hospital
        • physical_addressHoma Bay town
        • contact_details0724579750
        • contact_personJairus Oketch
        • site_capacity(null)
        • misc(null)
        • created2018-03-07 16:27:37
        • modified2020-02-03 10:55:38
        • County(array)
          • id43
          • county_nameHoma Bay
          • created2012-06-15 10:27:10
          • modified2012-06-15 10:27:10
      • 1(array)
        • id533
        • application_id655
        • county_id42
        • site_nameJaramogi Oginga Odinga Teaching and Referral Hospital
        • physical_addressKisumu town
        • contact_details0724817266
        • contact_personGodfrey Owino
        • site_capacity(null)
        • misc(null)
        • created2018-03-08 12:14:17
        • modified2020-02-03 10:55:38
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id331
        • application_id655
        • sponsorWeill Cornell Medical College
        • sponsor_type
        • contact_personRichard Lee
        • address425 E. 61st St., 12th Fl, NY, NY 10065
        • telephone_number+1646-962-4811
        • fax_number
        • cell_number+1646-962-4811
        • email_addressril9010@med.cornell.edu
        • created2018-03-07 16:27:37
        • modified2020-02-03 10:55:38
  • 3(array)
    • Application(array)
      • id654
      • user_id32
      • trial_status_id5
      • abstract_of_study<div style=\"text-align: justify;\">\n In 2012, the WHO Strategic Advisory Group of Experts (SAGE) on immunizations made a recommendation for influenza vaccination of pregnant women. This was based upon compelling evidence of substantial risk of severe disease in this group and the safety and effectiveness of seasonal influenza vaccine in preventing disease in pregnant women as well as their young infants, in whom disease burden is also high. Sub-Saharan Africa has a high prevalence of HIV and malaria, the presence of which among expectant mothers can reduce response to influenza vaccination, and therefore affect transfer of vaccine-induced antibodies to their newborn babies. There is no documention on the effect of malaria parasitemia on influenza vaccination in pregnant women and their newborns. Few studies have shown reduced immunogenicity of influenza vaccine and associated antibody transfer among pregnant women with HIV, however the studies were done late in the course of pregnancy. We propose to conduct an influenza vaccine demonstration project, using an Inactivated Influenza Vaccine (IIV) already licensed in Kenya to vaccinate pregnant women in a high HIV prevalence and malaria-endemic setting in western Kenya. Documentation of vaccine-induced antibody transfer from vaccinated mothers to their babies is essential and key to informing the Kenya Ministry of Health on maternal immunization policy and strategy for these high-risk groups. Western Kenya is a resource-limited setting with high burden of influenza disease among infants. Vaccinating pregnant women for better outcomes in both mother and infant would therefore be a cost effective strategy in preventing influenza disease in two high-risk groups. Data from this study will also help inform influenza vaccine deployment in other countries with similar HIV and malaria profiles. If adopted by the government, maternal influenza immunization could be an important public health strategy in resource constrained settings to protect infants <6 months, not eligible for influenza vaccination themselves, and their mothers from influenza disease and associated complications.</div>\n<div>\n  </div>\n
      • study_title<p>\n Impact of HIV Infection and Malaria Parasitemia on Immunogenicity of Inactivated Influenza Vaccine in Pregnant Women and on Mother-to-Child Vaccine-induced Antibody Transfer</p>\n
      • laymans_summary<p>\n Studies have shown that influenza can be severe among pregnant women and newborn babies. Influenza vaccination during pregnancy can protect pregnant women. Also, women vaccinated against influenza during pregnancy can pass on protective antibodies to their babies who are too young (<6 months of age) to be directly vaccinated. Influenza vaccination has been offered to pregnant women around the world for many years and data show the vaccine to be safe, for the mother and their unborn babies. Based on evidence from such studies, the advisory group of experts on immunization from the WHO recommended influenza vaccination to pregnant women. Sub-Saharan Africa has a high percentage of the population suffering from HIV and malaria; these diseases may affect how pregnant women respond to influenza vaccine and therefore affect the amount of protection transfered to their newborn babies. We propose to carry out a demonstration project using an influenza vaccine licensed in Kenya to vaccinate pregnant women in a setting of western Kenya with high rates of HIV among the population and malaria presence throughout the year. Results from this study will inform the Ministry of Health on policy and startegies for vaccinating mothers to protect these two high-risk groups. These results will also be applicable to other countries with similar HIV and malaria burden and may inform their policies on vaccination of pregnant women.</p>\n
      • short_titleMaternal Influenza Vaccine Study
      • protocol_noECCT/18/04/02
      • version_no1.1
      • date_of_protocol03-11-2017
      • study_drugInactivated Influenza Vaccine
      • disease_conditionInfluenza
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstonysangke@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Tony Sang
      • declaration_date103-05-2018
      • declaration_principal_investigatorNancy Otieno
      • declaration_date203-05-2018
      • placebo_presentNo
      • study_objectives<div>\n Primary Objectives</div>\n<ol>\n <li>\n To evaluate the immunogenicity of IIV in HIV-infected pregnant women and women with peripheral malaria parasitemia at the time of vaccination.</li>\n <li>\n To evaluate the level of vaccine-induced influenza antibody transfer to infants of HIV-infected and uninfected pregnant women who receive IIV early in pregnancy.</li>\n <li>\n To evaluate the level of vaccine-induced influenza antibody transfer to infants of mothers who had peripheral malaria parasitemia by Rapid Diagnostic Test for malaria at the time of influenza vaccination during pregnancy.</li>\n</ol>\n<div>\n  </div>\n<div>\n Secondary Objectives</div>\n<ol>\n <li>\n To evaluate the impact of HIV infection and peripheral malaria parasitemia on the duration of influenza vaccine-induced antibodies transferred to infant.</li>\n</ol>\n
      • principal_inclusion_criteria<ol>\n <li>\n Pregnancy confirmed by rapid urine pregnancy test for hCG or ultrasound</li>\n <li>\n Should have a singleton current pregnancy</li>\n <li>\n ≤20 weeks’ gestation by ultrasound, fundal height, or within 4 weeks of quickening</li>\n <li>\n Consents to HIV testing and counseling as required</li>\n <li>\n Does not plan to relocate out of the study area or population-based surveillance site in the next 15 months and agrees to all follow-up visits and study procedures.</li>\n <li>\n Provides informed consent by signature or thumb print</li>\n <li>\n Not currently enrolled in another intervention study</li>\n <li>\n Must be willing to deliver in the labor ward of the study hospital</li>\n <li>\n No history of chronic illness requiring multiple hospitalizations or prolonged medical therapy (except HIV on HAART)</li>\n</ol>\n
      • principal_exclusion_criteria<ol>\n <li>\n History of allergic reaction to any component of the study vaccine (e.g allergy to eggs or chicken products)</li>\n <li>\n Planning to relocate out in the 15 months following enrollment</li>\n <li>\n Received immunoglobulin or blood products within 45 days of study entry</li>\n <li>\n Used immunosuppressive medication within 45 days of study entry (inhaled and topical corticosteroids permitted)</li>\n <li>\n Multiple pregnancy (twins, triplets, etc.)</li>\n <li>\n Current enrollment in another interventional study</li>\n <li>\n Gestational age >20 weeks by last menstrual period or fundal height</li>\n <li>\n Hemoglobin <7.0 g/dL</li>\n <li>\n Influenza vaccination in previous 12 months</li>\n <li>\n Unable to give informed consent (for example due to mental disability).</li>\n <li>\n Acutely ill with temperature ≥37.5°C Axillary/38°C Oral on the day of vaccination (will be deferred and can be enrolled after treatment and fever is resolved).</li>\n</ol>\n
      • primary_end_points<ol>\n <li>\n To evaluate the immunogenicity of IIV in HIV-infected pregnant women and women with peripheral malaria parasitemia at the time of vaccination.</li>\n <li>\n To evaluate the level of vaccine-induced influenza antibody transfer to infants of HIV-infected and uninfected pregnant women who receive IIV early in pregnancy.</li>\n <li>\n To evaluate the level of vaccine-induced influenza antibody transfer to infants of mothers who had peripheral malaria parasitemia by Rapid Diagnostic Test for malaria at the time of influenza vaccination during pregnancy.</li>\n</ol>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • 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_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<div style=\"text-align: justify;\">\n <div>\n The study is to be conducted in Siaya County at two study sites namely Siaya County Referral Hospital (SCRH)and Bondo Sub-county Referral Hospital (BSRH). These are among the largest hospitals in the county with adequate equipment and structures. Siaya County Referral hospital has a Clinical Research Centre(CRC) and this is where the study will be conducted. The study personnel that will handle the study participants are well trained professionally and all of them have undergone intensive Good Clinical Practice(GCP) training. Most of the study staffs have participated in other previous clinical trials and therefore have the expertise and experience of the same.</div>\n <div>\n  </div>\n <div>\n The study is be headed by Dr. Sandra Shaves who is a medical doctor and Nancy Otieno both of which have vast experience in research in human subjects, they are the Principal Investigators, among the Coinvestigator there is Michael Otieno who is also the study coordinator, Michael is a clinical officer with a lot experience of about 8 years in clinical trials, he has worked in Rotateq Vaccine clinical trial and Malaria vaccine clinical trials, the study doctor is Dr. Allan Dungani who is also participating in Malaria vaccine clinical trial as study doctor. Dr. Tony Sang is the study pharmacist. Dr. Sang is well experienced in handling the clinical trials with more than 10 years on the same. He has participated in more than 3 vaccine clinical trials and many drug trials. The study has 10 nurses, 3 clinicians, 6 lab technologists, 3 quality assurance officers, data manager and analysts, and 10 field technicians.</div>\n <div>\n  </div>\n <div>\n The laboratory department where the samples will be handled and processed before shipment for further analysis and even stored has undergone the ISO certification. The lab staffs have all undergone the good clinical and laboratory practice training (GCLP), the lab staffs have as well participated in previous clinical trials</div>\n <div>\n  </div>\n <div>\n The clinical staffs that will be directly involved in handling the study participants have adequate skills to manage and handle any eventuality that may arise in the course of the duration of the study. Adequate preparation has been made in terms of equipment and other supplies required for the study All the staffs have undergone the protocol training and are well conversant with the study design and procedures.</div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial is to be conducted in Kenya due to the high prevalence of HIV and malaria.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<ol>\n <li>\n KEMRI Scientific & Ethics Review Unit approved this protocol as per letter dated XXXXXXX</li>\n</ol>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration2.5 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_siteSiaya - 156\nBondo - 156
      • total_participants_worldwide312
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameNancy
      • investigator1_middle_name
      • investigator1_family_nameOtieno
      • investigator1_qualificationMA, PhDc
      • investigator1_professional_addressKEMRI-CGHR, Kisumu, Kenya
      • investigator1_telephone+254 720 661 245
      • investigator1_emailnotieno@gmail.com
      • organisations_transferred_No
      • number_participants312
      • notification
      • approval_date04-06-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted08-05-2020
      • 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)
      • modified2024-01-31 09:04:07
      • created2018-02-22 10:14:08
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id413
        • application_id654
        • given_nameSandra
        • middle_nameS
        • family_nameChaves
        • qualificationMD, MSc
        • professional_addressUS Centers for Disease Control and Prevention (CDC), Nairobi, Kenya
        • telephone+254 20 2867 000
        • emailSChaves@cdc.gov
        • created2018-02-22 10:16:45
        • modified2020-05-08 11:23:15
    • SiteDetail(array)
      • 0(array)
        • id530
        • application_id654
        • county_id41
        • site_nameSiaya County Referral Hospital
        • physical_addressSiaya Town
        • contact_detailsP.O. Box 144-60400
        • contact_personNancy Otieno
        • site_capacity(null)
        • misc(null)
        • created2018-02-22 10:16:45
        • modified2020-05-08 11:23:15
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id531
        • application_id654
        • county_id41
        • site_nameBondo Sub-County Hospital
        • physical_addressBondo Town
        • contact_detailsP.O Box 595-40601
        • contact_personNancy Otieno
        • site_capacity(null)
        • misc(null)
        • created2018-02-22 11:59:52
        • modified2020-05-08 11:23:15
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id330
        • application_id654
        • sponsorUS Centers for Disease Control and Prevention, Influenza Division
        • sponsor_typeResearch Institution
        • contact_personSandra S Chaves
        • addressUS Centers for Disease Control and Prevention (CDC), Nairobi, Kenya
        • telephone_number+254 710 602 748
        • fax_number
        • cell_number+254 20 2867 000
        • email_addressschaves@cdc.gov
        • created2018-02-22 10:16:45
        • modified2020-05-08 11:23:15
  • 4(array)
    • Application(array)
      • id679
      • user_id360
      • trial_status_id5
      • abstract_of_study<p>\n This study aims to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine</p>\n<p>\n (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated <em>P. falciparum </em>malaria.</p>\n<p>\n  is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.</p>\n<p>\n The primary objective of this study is to determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by</p>\n<p>\n <em>P. falciparum</em>. The primary efficacy endpoint is the polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) at Day 29.</p>\n<p>\n This will be a multicenter and open-label study with a single cohort PK Run-in Part followed by 2 randomized, parallel-group parts in adults and children with confirmed and uncomplicated <em>P. falciparum</em> malaria.</p>\n<p>\n The study population will consist of male and female patients (PK Run-in Part and Part A: ≥ 12 years old and ≥ 35.0 kg; Part B: 2 to <12 years old and ≥ 10.0 kg) with confirmed and uncomplicated <em>P.</em></p>\n<p>\n <em>falciparum </em>malaria. The plan is to enroll and treat 12 patients in PK Run-in Part and randomize approximately 500 patients in Parts A and B (325 in Part A and up to 175 in Part B) in approximately 15 sites in Africa and Asia.</p>\n
      • study_title<p>\n <b><span style=\"font-family: "Times New Roman", serif; font-size: 12pt;\">A Phase 2 interventional, multicenter, randomized open-label study to determine the effective and tolerable dose of KAF156 and Lumefantrine Solid Dispersion Formulation in combination, given once daily for 1, 2 and 3-days to adults and children with uncomplicated <i>Plasmodium falciparum </i>malaria.</span></b></p>\n
      • laymans_summary<p>\n This was a study to test the new anti-malaria drug ganaplacide (KAF156) in combination with lumefantrine (LUM-SDF). This is a new drug that can also work in malaria parasites that are resistant to the drugs that are now used. It is also easier to use since it can be taken once daily.</p>\n<p>\n The study was done in patients with an acute malaria infection. Clinics and patients from several countries in Africa and Asia took part in the study. In total 524 patients: adults and children above 2 years of age. 48 of those patients received a control treatment (Coartem^®) to see if the new drug would work the same, worse, or better.</p>\n<p>\n The goal of this study was to test how good this new drug works to remove the malaria parasite from the patient’s blood. Also, the side effects of the drug were recorded. Another purpose was to find the best possible dose of the medication.</p>\n<p>\n The results of the study showed that the new drug KAF156/LUM-SDF was effectively removing the malaria parasite in patients of all ages and cured the patients from the malaria infection. The best effect was seen when the drug was given for 3 days (one time per day). The effect was like the effect of the control drug Coartem^®.</p>\n<p>\n The side effects of the drug KAF156/LUM-SDF were not very strong and like the control treatment Coartem^®. Some patients complained of headache, vomiting, stomach pain and tiredness. These are also symptoms of the malaria infection. The blood tests and heart tests did not show any sign of danger for the new drug.</p>\n<p>\n Conclusion of the study is that the new drug ganaplacide + lumefantrine works well and is safe. It should be given for 3 days and will now be tested in other studies with more patients. If the results of these studies are also good, the drug will be made available to doctors and patients.</p>\n
      • short_titleCKAF156 STUDY
      • protocol_noECCT/18/04/01
      • version_noVersion No: Version 02
      • date_of_protocol14-02-2017
      • study_drugKAF156 and LUM-SDF in combination and Coartem as control arm
      • disease_conditionMALARIA
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdotigondi3@gmail.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_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data0
      • 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_plan0
      • applicant_contractual_agreement1
      • declaration_applicantDR Bernhards Ogutu
      • declaration_date126-05-2018
      • declaration_principal_investigatorDr Bernhards Ogutu
      • declaration_date226-05-2018
      • placebo_presentNo
      • study_objectives<p>\n Primary Objective To determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by P. falciparum. The primary efficacy endpoint is the polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) at Day 29. Secondary Objectives 1: To evaluate the safety and tolerability of KAF156/LUM-SDF. 2: To further assess the effect of treatment with KAF156/LUM-SDF by assessing uncorrected ACPR and corrected ACPR at additional time points, as well as fever- and parasite clearance times. 3: To assess key pharmacokinetic (PK) parameters of KAF156 and lumefantrine.</p>\n
      • principal_inclusion_criteria<div>\n <p>\n . PK Run-in Part and Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg Part B: or ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included</p>\n <p>\n 2. Microscopic confirmation of <em>P. falciparum </em>by Giemsa-stained thick and thin films</p>\n <p>\n 3. <em>P. falciparum </em>parasitaemia of more than 1000 and less than 150 000 parasites/μL at the time of pre-screening.</p>\n <p>\n 4. Axillary temperature ≥ 37.5 ºC or documented history of fever during the previous 24 hours.</p>\n <p>\n 5. Negative pregnancy test for women of child bearing potential (WOCBP)</p>\n <p>\n 6. Signed informed consent and or assent</p>\n <p>\n 7. The patient or his/her parent/legal guardian (in case of pediatric patients) is able to</p>\n <p>\n understand and comply with protocol requirements, instructions and protocol-stated</p>\n <p>\n restrictions and is likely to complete the study as planned</p>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div>\n <p>\n . Mixed <em>Plasmodium </em>infections</p>\n <p>\n 2. Signs and symptoms of severe malaria according to WHO 2015 criteria unless</p>\n <p>\n characterized by high parasitaemia only</p>\n <p>\n 3. Active infections including tuberculosis</p>\n <p>\n 4. Patients with concurrent febrile illnesses (e.g., typhoid fever)</p>\n <p>\n 5. History of, or current alcohol misuse/abuse defined as five or more drinks on the same occasion on each of 5 or more days in the past 30 days</p>\n <p>\n 6. Known relevant liver disease e.g. chronic hepatitis, cirrhosis, compensated or</p>\n <p>\n decompensated, history of hepatitis B or C, hepatitis B or A vaccination in last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis</p>\n <p>\n 7. Any confirmed or suspected immunosuppressive or immunodeficient condition,</p>\n <p>\n including human immunodeficiency virus (HIV) infection</p>\n <p>\n 8. Severe malnutrition (body mass index (BMI) < 16.0 for patients ≥ 12 years, and less</p>\n <p>\n than 70% of median normalized WHO reference weight for children < 12 years)</p>\n <p>\n 9. Severe vomiting, defined as more than 3 times in the 24 hours prior to inclusion in the</p>\n <p>\n study or severe diarrhea defined as more than 3 watery stools per day</p>\n <p>\n 10. Pregnant or nursing (lactating) women</p>\n <p>\n 11. Sexually active patients not willing to practice effective contraception</p>\n <p>\n 12. Sexually active males must use a condom during intercourse while taking drug and for the duration of the study and should not father a child in this period. A condom is</p>\n <p>\n required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid</p>\n <p>\n 14. Active duodenal ulcer, ulcerative colitis, Crohn’s disease, chronic (i.e., > 2 weeks) use of non-steroidal anti-inflammatory drugs (NSAIDs)</p>\n <p>\n 15. Clinically relevant abnormalities of electrolyte balance which require correction, e.g.,</p>\n <p>\n hypokalemia, hypocalcemia or hypomagnesemia.</p>\n <p>\n 16. Anemia (Hemoglobin level < 8 g/dL)</p>\n <p>\n 17. Any surgical or medical condition which might significantly alter the absorption,</p>\n <p>\n distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in</p>\n <p>\n case of participation in the study.</p>\n <p>\n 18. Resting QTcF > 450 ms (males), QTcF > 460 ms (females) at screening</p>\n <p>\n 19. Creatinine > 2 x ULN in the absence of dehydration. In the case of dehydration, the</p>\n <p>\n creatinine should be < 2 x ULN after oral/parenteral rehydration</p>\n <p>\n  </p>\n <p>\n 20. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or <em>in situ </em>cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases</p>\n <p>\n 21. Known chronic underlying disease such as sickle cell disease, and severe cardiac, renal, or hepatic impairment</p>\n <p>\n 22. Known active or uncontrolled thyroid disease</p>\n <p>\n 23. Inability to tolerate oral medication (in tablet and/or liquid form)</p>\n <p>\n <strong>Interfering substances</strong></p>\n <p>\n 24. Patients with prior antimalarial therapy or antibiotics with antimalarial activity within</p>\n <p>\n minimum of their five (5) plasma half-lives (or within 4 weeks of screening if half-life is</p>\n <p>\n unknown)</p>\n <p>\n 25. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or</p>\n <p>\n until the expected pharmacodynamic effect has returned to baseline, whichever is longer</p>\n <p>\n 26. Patients taking medications prohibited by the protocol (see Section 5.6.8, Table 5-55)</p>\n <p>\n 27. Previous participation in any malaria vaccine study or received malaria vaccine in any</p>\n <p>\n other circumstance</p>\n <p>\n <strong>Specific to the study</strong></p>\n <p>\n 28. History or family history of long QT syndrome or sudden cardiac death, or any other</p>\n <p>\n clinical condition known to prolong the QTc interval, such as history of symptomatic</p>\n <p>\n cardiac arrhythmias, clinically relevant bradycardia or severe heart disease</p>\n <p>\n 29. Use of agents known to prolong the QT interval unless it can be permanently</p>\n <p>\n discontinued for the duration of study</p>\n <p>\n 30. History of hypersensitivity to any of the study drugs or its excipients or to drugs of</p>\n <p align=\"left\">\n similar chemical classes</p>\n</div>\n<p>\n  </p>\n
      • primary_end_points<table align=\"center\" cellpadding=\"0\" cellspacing=\"0\" hspace=\"0\" vspace=\"0\" width=\"616\">\n <tbody>\n <tr>\n <td align=\"left\">\n <p style=\"margin-left: 8pt;\">\n . Standard safety/tolerability assessments: AE incidence and severity, liver and kidney function tests and electrocardiogram (ECG) abnormalities.</p>\n <p style=\"margin-left: 8pt;\">\n  </p>\n <p style=\"margin-left: 8pt;\">\n 2. PCR-Uncorrected ACPR at Days 15, 29 and 43 (i.e., 14, 28 and 42 days postdose). PCR-corrected ACPR at Days 15 and 43 (i.e., 14 and 42 days post-dose).</p>\n <p style=\"margin-left: 8pt;\">\n 3. Incidence rate of recrudescence and reinfection at Days 15, 29 and 43. Parasite and Fever Clearance Times(PCT and FCT).</p>\n <p style=\"margin-left: 8pt;\">\n 4. Proportion of patients with parasitaemia at 12, 24, and 48 hours after treatment.</p>\n <p style=\"margin-left: 8pt;\">\n 5. PK assessments</p>\n </td>\n </tr>\n </tbody>\n</table>\n<div style=\"clear: both;\">\n  </div>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • 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<table align=\"center\" cellpadding=\"0\" cellspacing=\"0\" hspace=\"0\" vspace=\"0\" width=\"616\">\n <tbody>\n <tr>\n <td align=\"left\">\n <p>\n Number of staff, names, qualifications, experience -- including study co facilities, emergency facilities, other relevant infrastructure)</p>\n <p>\n  </p>\n <p>\n The Kombewa Clinical Trials Center is a two-story, 836 m² building and a two-story, 450 m² annex block which includes office spaces, a secure records archive room, a clinical laboratory, a phlebotomy room, an outpatient facility that includes six examination/consultation rooms, an urgent care treatment area and a pharmacy. Only qualified study staff who are in the study delegation log will conduct the study.</p>\n <p>\n During conduct of clinical trials, the Clinical Trials Center is staffed at all times (24 hours a day, 7 days a week) by  clinical officers and community nurses, medical officers (physicians) and pediatricians among others.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<div style=\"clear: both;\">\n  </div>\n<p>\n  </p>\n
      • other_details_explanation<div style=\"margin-left: 8pt;\">\n <p>\n <strong>The study is being done in malaria endemic regions which include Africa and Asia</strong></p>\n</div>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration2 years
      • 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_comparatorLumefantrine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites2
      • multi_country_list Burkina Faso, Gabon, Gambia, Kenya, Mali, Mozambique and Uganda
      • data_monitoring_committeeYes
      • total_enrolment_per_siteApproximately 120
      • total_participants_worldwide500
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • 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_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationPHD
      • investigator1_professional_addressP.O BOX 54, 40100
      • investigator1_telephone+254 733 966065 or +254 733 333 530
      • investigator1_emailbernhards.ogutu@usamru-k.org
      • organisations_transferred_Yes
      • number_participantsApproximately 120 subjects
      • notification
      • approval_date23-08-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted22-04-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n <strong>Name of product:</strong> KAF156 and LUM-SDF</p>\n<p>\n <strong>Protocol identification number:</strong> Protocol no. CKAF156A2202, EudraCT no.: 2020-003284-25</p>\n<p style=\"margin-left:3.0pt;\">\n <strong>Title of study</strong>: A Phase 2 interventional, multicenter, randomized open-label study to determine the effective and tolerable dose of KAF156 and lumefantrine Solid Dispersion Formulation in combination, given once daily for 1, 2 and 3 days to adults and children with uncomplicated <em>Plasmodium falciparum</em> malaria</p>\n<p>\n <strong>Principal or Coordinating Investigator</strong>: Martin Peter Grobusch M.D, PhD, FRCP, Centre de Recherches Médicales de Lambaréné, CERMEL, Albert Schweitzer Hospital, BP242 Lambarene, Gabon.</p>\n<p>\n <strong>Study center(s):</strong> 13 centers in 10 countries: Uganda (2 centers), Kenya (2 centers), Cote d'Ivoire (2 centers), Vietnam, Thailand, Burkina Faso, Gabon, Mozambique, Mali, India</p>\n<p>\n <strong>Publication (reference):</strong> None</p>\n<p>\n <strong>Study period</strong></p>\n<p>\n Study initiation date: 02‑Aug‑2017 (first patient first visit)</p>\n<p>\n Study completion date: 28‑Jun‑2021 (last patient last visit)</p>\n<p>\n <strong>Phase of development (phase of this clinical study)</strong>: II</p>\n<p>\n <strong>Objectives</strong>: The primary objective was to determine the effective doses of KAF156 combined with LUM‑SDF given daily over 1, 2, or 3 days for treatment of uncomplicated malaria caused by <em>P. falciparum</em>.</p>\n<p>\n The secondary objectives were to evaluate the safety and tolerability of KAF156/LUM‑SDF, to further assess the treatment effect of KAF156/LUM‑SDF by assessing uncorrected and PCR-corrected ACPR at additional time points, as well as fever and parasite clearance times, and to assess the key pharmacokinetic (PK) parameters of KAF156 and lumefantrine.</p>\n<p>\n The study has been completed as planned.</p>\n<p>\n <strong>Methodology:</strong> This was a multicenter, open-label, randomized, parallel-group study to determine the most effective and tolerable dose at the shortest dosing regimen (3-, 2- and 1-day regimens) of a combination of KAF156 and a solid dispersion formulation of lumefantrine (LUM-SDF) in adults and children with uncomplicated <em>P. falciparum</em> malaria. The study had a PK Run-in part and two main parts: Part A and Part B. In the PK Run‑in part, male and female adult/adolescent patients (≥ 12 years old and ≥ 35 kg) were administered a single KAF156/LUM‑SDF dose to assess potential PK interactions. In Part A, male and female adult/adolescent patients (≥ 12 years old and ≥ 35 kg) were randomized into one of seven cohorts (six KAF156 and LUM-SDF cohorts and a control arm - Coartem) in a 2:2:2:2:2:2:1 ratio. Patients were admitted to the hospital on Day 1, were dosed on Day 1 only, Days 1 and 2, or Days 1, 2, and 3, depending on the assigned treatment cohort, and were discharged on Day 4. Patients were then followed up until Day 43. Upon completion of Part A, all the dosing groups were evaluated in an interim assessment to determine the effective and tolerated KAF156 and LUM-SDF dosing regimen and dosages to be used in Part B. In Part B, children (2 to < 12 years old and ≥ 10 kg) with uncomplicated <em>P. falciparum</em> malaria were randomized to the three selected KAF156 and LUM-SDF cohorts and Coartem in a 2:2:2:1 ratio.</p>\n<p>\n <strong>Number of subjects (planned and analyzed)</strong>: In the PK Run‑in part, 12 patients were planned to be enrolled, and 12 patients were enrolled and analyzed. In Part A, approximately 325 patients were planned to be enrolled, and 337 patients were enrolled and analyzed. In Part B, approximately 175 patients were planned to be enrolled, 175 patients were enrolled, and 174 patients were analyzed (1 patient did not receive the study treatment).</p>\n<p>\n <strong>Diagnosis and main criteria for inclusion: </strong>Male or female patients ≥ 12 years old and ≥ 35 kg (PK Run‑in part and Part A) or 2 to < 12 years old and ≥ 10 kg (Part B) with confirmed and uncomplicated <em>P. falciparum</em> malaria (microscopic confirmation by Giemsa‑stained thick and thin films) and <em>P. falciparum</em> counts more than 1000 and less than 150000 parasites/μL at pre‑screening, and axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.0ºC, or similar history of fever during the previous 24 hours.</p>\n<p>\n <strong>Duration of treatment</strong>: In the PK Run‑in part, KAF156/LUM‑SDF was administered QD for 1 day. In Part A and Part B, KAF156/LUM‑SDF was administered QD for 1 day, 2 days, or 3 days, while Coartem was administered BID for 3 days.</p>\n<p>\n <strong>Test and reference therapies, dose and mode of administration, batch number</strong>: In the PK Run-in part, KAF156 200 mg and LUM‑SDF 960 mg was administered orally. The dosing scheme followed for KAF156/LUM‑SDF and Coartem in Part A and Part B is given below:</p>\n<p>\n <strong>Part A: KAF156 and LUM-SDF dosing scheme</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <thead>\n <tr>\n <th style=\"width:66px;\">\n <p>\n <strong>Cohort</strong></p>\n </th>\n <th style=\"width:237px;\">\n <p align=\"center\">\n <strong>Treatment</strong></p>\n </th>\n <th style=\"width:151px;\">\n <p align=\"center\">\n <strong>Dose</strong></p>\n </th>\n <th style=\"width:151px;\">\n <p align=\"center\">\n <strong>Dosing regimen</strong></p>\n <p align=\"center\">\n <strong>(oral administration)</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:66px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:237px;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n 400 mg/960 mg</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n QD for 1 day</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:66px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:237px;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n 800 mg/960 mg</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n QD for 1 day</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:66px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:237px;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n 400 mg/960 mg</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n QD for 2 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:66px;\">\n <p>\n 4</p>\n </td>\n <td style=\"width:237px;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n 200 mg/480 mg</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n QD for 3 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:66px;\">\n <p>\n 5</p>\n </td>\n <td style=\"width:237px;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n 400 mg/480 mg</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n QD for 3 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:66px;\">\n <p>\n 6</p>\n </td>\n <td style=\"width:237px;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n 400 mg/960 mg</p>\n </td>\n <td style=\"width:151px;\">\n <p align=\"center\">\n QD for 3 days</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n <strong>Part B: KAF156 and LUM-SDF dosing scheme*</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:100.0%;\" width=\"100%\">\n <thead>\n <tr>\n <th style=\"width:43.88%;\">\n <p align=\"center\">\n <strong>Treatment</strong></p>\n </th>\n <th style=\"width:28.06%;\">\n <p align=\"center\">\n <strong>Dose</strong></p>\n </th>\n <th style=\"width:28.06%;\">\n <p align=\"center\">\n <strong>Dosing regimen</strong></p>\n <p align=\"center\">\n <strong>(oral administration)</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:43.88%;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:28.06%;\">\n <p align=\"center\">\n 400 mg/960 mg</p>\n </td>\n <td style=\"width:28.06%;\">\n <p align=\"center\">\n QD for 1 day</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:43.88%;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:28.06%;\">\n <p align=\"center\">\n 400 mg/960 mg</p>\n </td>\n <td style=\"width:28.06%;\">\n <p align=\"center\">\n QD for 2 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:43.88%;\">\n <p align=\"center\">\n KAF156/LUM-SDF</p>\n </td>\n <td style=\"width:28.06%;\">\n <p align=\"center\">\n 400 mg/960 mg</p>\n </td>\n <td style=\"width:28.06%;\">\n <p align=\"center\">\n QD for 3 days</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n Doses for KAF156/LUM-SDF in the table are for patients > 35 kg. For patients with lower body weights, these were adapted as follows: 25 to< 35 kg. 0.75 of the adult dose, 15 to < 25 kg: 0.50 of the adult dose, 10 to < 15 kg: 0.25 of the adult dose. These are the same weight brackets and corrections as for Coartem.</p>\n<p>\n <strong>Coartem dosing per weight (Parts A and B)</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:100.0%;\" width=\"100%\">\n <thead>\n <tr>\n <th style=\"width:33.32%;\">\n <p>\n <strong>Weight</strong></p>\n </th>\n <th style=\"width:33.34%;\">\n <p align=\"center\">\n <strong>Dose (artemether/lumefantrine)</strong></p>\n </th>\n <th style=\"width:33.34%;\">\n <p align=\"center\">\n <strong>Dosing regimen</strong></p>\n <p align=\"center\">\n <strong>(oral administration)</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:33.32%;\">\n <p>\n ≥ 12 years and ≥ 35.0 kg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n 80/480 mg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n BID for 3 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:33.32%;\">\n <p>\n 25.0 to < 35.0 kg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n 60/360 mg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n BID for 3 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:33.32%;\">\n <p>\n 15.0 to < 25.0 kg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n 40/240 mg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n BID for 3 days</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:33.32%;\">\n <p>\n 10.0 to < 15.0 kg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n 20/120 mg</p>\n </td>\n <td style=\"width:33.34%;\">\n <p align=\"center\">\n BID for 3 days</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n <strong>Criteria for evaluation</strong></p>\n<p>\n <strong>Efficacy</strong>: Efficacy assessments were based on polymerase chain reaction (PCR)‑corrected adequate clinical and parasitological response (ACPR) at Day 29. For parasitemia assessment, thick and thin blood films were evaluated using Giemsa stain and were used to quantify each parasite species and <em>P. falciparum</em> gametocytes. Microscopic species identification of parasites was confirmed and determined with PCR‑based methods on blood samples.</p>\n<p>\n <strong>Pharmacokinetics:</strong> Blood samples were collected for rich PK sampling in the PK Run-in Part and in some patients in Part A and sparse PK sampling in Part A (in the rest of the patients not involved in rich PK) and in Part B. Parameters such as AUCinf, AUClast, AUC0-t, Cmax, and Tmax were reported, where possible for the patients with rich PK data using non-compartmental method of analysis (using Phoenix 6.4 or higher).</p>\n<p>\n <strong>Safety</strong>: Safety assessments consisted of collecting all adverse events (AEs), serious adverse events (SAEs), along with their severity and relationship to the study treatment. This included physical examination and malaria signs and symptoms, regular monitoring of vital signs, body temperature, laboratory evaluations (hematology, blood chemistry, and urinalysis), electrocardiogram (ECG), pregnancy and assessments of fertility.</p>\n<p>\n <strong>Statistical methods</strong>: Statistical analyses for the PK Run-in part, Part A, and Part B were performed separately. Subgroups, which included age‑groups, baseline weight‑groups, sex, and region, were used for descriptive summary of selected efficacy and safety analyses. For key efficacy and safety outcome, pooled analysis was performed by pooling Part B and corresponding cohorts in Part A. Unless described separately, the same statistical method was used for separate analysis and pooled analysis.</p>\n<p>\n <u>Efficacy</u>: The PK Run-in part was analyzed separately. The objective for the PK Run-in part was to investigate the pharmacokinetic interaction potential between KAF156 and lumefantrine.</p>\n<p>\n The primary efficacy variable was PCR‑corrected ACPR at Day 29. A patient was considered as PCR‑corrected ACPR at Day 29 if the patient did not meet any of the criteria of early treatment failure (up to Day 4), late clinical failure (Day 5 to Day 29) or late parasitological failure (Day 8 to Day 29), and has absence of parasitemia on Day 29 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation (Day 8 or later) was considered as a reinfection only if the original parasitemia cleared before Day 8 and none of the parasite strain(s) detected on Day 8 or later match with the parasite strain at baseline based on PCR genotyping. Treatment failures after 7 days due to reinfection based on PCR genotyping were not considered as failure for PCR-corrected analyses but were considered as failure for uncorrected analyses.</p>\n<p>\n The statistical null hypothesis was that the ACPR rate at Day 29 is at most 80%. The alternative hypothesis was that the ACPR rate at Day 29 is greater than 80%. The statistical hypothesis was evaluated using the lower limit of 2-sided 95% exact confidence interval (CI) (Clopper-Pearson method) for the ACPR rate at Day 29. If the lower limit of 2-sided 95% exact CI for the ACPR rate at Day 29 is greater than 80%, the null hypothesis is rejected. The statistical hypothesis testing was evaluated separately for each KAF156 and LUM-SDF combination in each part based on the per‑protocol set (PPS). There was no adjustment for multiplicity for this Phase II study.</p>\n<p>\n Supportive analysis of the primary endpoint (for the full analysis set; FAS) was performed using the Kaplan‑Meier method. In order to assess the impact of reinfections on the PCR‑corrected ACPR rate, sensitivity analysis was performed. PCR‑corrected ACPR rate was recalculated by excluding the patients with reinfections occurring prior to Day 29. Analyses were based on PPS for Part A and Part B.</p>\n<p>\n Secondary endpoints:</p>\n<ul>\n <li>\n PCR‑corrected ACPR (at Day 15 and 43) and uncorrected ACPR (at Day 15, 29, and 43): At each visit, the mean ACPR rate with 95% CI was provided using Clopper-Pearson method for each treatment group. In addition, PCR-corrected ACPR rate was calculated and plotted using the Kaplan-Meier method for each treatment group in the FAS. For uncorrected ACPR at Day 29, a sensitivity analysis was performed to assess the impact of administration of non-study antimalarial drugs on the PCR uncorrected response rate. The proportion of patients with PCR uncorrected ACPR at Day 29 was recalculated by considering the patients receiving non-study antimalarial drugs (if received before Day 29 visit without being treatment failures i.e. not early treatment failures or late clinical failures or late parasitological failures) as non-responders using FAS. Patients who received concomitant prohibited non-malaria medications with potential impact on efficacy/antimalarial activity (PROH01b) before the Day 29 visit without being treatment failures were also considered as non-responders.</li>\n</ul>\n<ul>\n <li>\n Treatment failure related parameters: 95% CI were provided for each treatment group using the Clopper‑Pearson method for the proportion of patients with parasitemia at 12, 24, and 48 hours after treatment and for the proportion of patients with early treatment failure, late clinical failure, and late parasitological failure.</li>\n</ul>\n<ul>\n <li>\n Recrudescence and reinfection: Incidence rates of recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline) and reinfection (appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline) at Days 15, 29, and 43 were estimated by the Kaplan-Meier method based on the subset of FAS patients who had clearance of initial infection by Day 15. Time to event (recrudescence or reinfection) was calculated from the time of first study medication to the date of first event if a patient experienced the event and was censored at the time of last parasite assessment if a patient did not experience the event.</li>\n</ul>\n<ul>\n <li>\n Parasite clearance time and fever clearance time: Descriptive statistics were presented using the Kaplan‑Meier method. Parasite clearance time was calculated based on uncorrected parasite counts. Patients without parasite clearance for whatever reason were censored at the time of last parasite assessment. Patients who were enrolled on the basis of history of fever and did not subsequently have a fever at pre-dose were not included in the analysis of fever clearance time. Patients without fever clearance for whatever reason were censored at the time of last temperature assessment.</li>\n</ul>\n<p style=\"margin-left:.25in;\">\n Analyses of ACPRs (PCR-corrected or uncorrected) were based on the FAS and PPS. Analyses of other secondary efficacy variables were based on the FAS.</p>\n<p style=\"margin-left:.25in;\">\n The following additional analyses were performed for each part and the pooled Part A and Part B:</p>\n<ul>\n <li>\n For PCR-corrected and uncorrected ACPR rates, the 95% CIs for the difference between each test group (KAF156/LUM-SDF combination) and the control (Coartem) were provided using the Wilson uncorrected method. For the pooled analysis, the treatment differences versus control were evaluated using a Mantel-Haenszel estimate of the common risk difference stratified by part.</li>\n</ul>\n<ul>\n <li>\n For parasite clearance time and fever clearance time, the difference between each test group and control were evaluated using a log-rank test. Patients who did not experience a clearance were censored at the time of last relevant assessment (parasite or fever). For the pooled analysis, the log-rank test was stratified by Part.</li>\n</ul>\n<p>\n <u>Safety</u>: All safety analyses were performed using the Safety set. The assessment of safety and tolerability was based mainly on the number and percent of patients with treatment‑emergent adverse events (AEs), changes in laboratory values (hematology, blood chemistry, and urinalysis), and clinically notable changes in vital signs and ECG.</p>\n<p>\n <u>Pharmacokinetics</u>: Descriptive statistics of pharmacokinetic parameters were calculated using the PK analysis set and included arithmetic and geometric means, standard deviation, median, minimum and maximum. A separate PK analysis was performed for patients providing rich PK data. Parameters such as AUCinf, AUClast, AUC0-t, Cmax and Tmax were reported for the patients with rich PK data using non‑compartmental method of analysis (using Phoenix 6.4 or higher). For the PK Run-in part, two sided 90% CI for AUC0-24h, Cmax and Tmax PK parameters of KAF156 and lumefantrine were calculated by Part and treatment group using normal or log-normal approximation as applicable. Non‑compartmental PK analysis for patients with sparse data was also conducted and feasible PK parameters were reported. Concentration at a nominal time point of 168 hours post dose or any other time point identified as critical for cure was reported for all patients where feasible.</p>\n<p>\n <strong>Summary - Results</strong></p>\n<p>\n <strong>Demographic and background characteristics</strong>: The patient demographics were comparable across the treatment groups in Part A and Part B, respectively. The majority of patients were Black (Part A: 288 patients, 85.5%; Part B: 173 patients, 98.9%). In Part A, the median age of patients was 16 years (range: 11 to 62 years), median body weight was 51 kg (range: 35 to 89 kgs), and the majority of patients (311 patients, 92.3%) had their body mass index (BMI) in the range of 16 to ≤ 25 kg/m²; there was a higher proportion of males (182 patients, 54%) compared to females (155 patients, 46%). In Part B, the median age of patients was 6 years (range: 2 to 11 years), median body weight was 20.1 kg (range: 10.2 to 34.5 kgs), and the BMI was < 16 kg/m² for majority of patients (140 patients, 80%); there was a higher proportion of females (95 patients, 54.3%) compared to males (80 patients, 45.7%). In the pooled analysis, (including those treatment groups common in Part A and Part B), the demographic characteristics were similar across the treatment regimens. Of the 356 patients (Part A + Part B), the majority (276 patients; 77.5%) were < 18 years of age. The median age was 11.5 years (range: 2 to 60 years). The median body weight was 35.2 kg (range: 10.2 to 89 kgs), and the BMI ranged from 16 to ≤ 25 kg/m² for 203 patients (57%) and was < 16 kg/m² for 143 patients (40.2%). There was an equal proportion of males (181 patients, 50.8%) and females (175 patients, 49.2%).</p>\n<p>\n In both, Part A and Part B, patients either had fever at baseline or it was reported as a medical history. In some patients, the mean body temperature at baseline was not indicative of fever as these patients received anti-pyretic drugs. In Part A and Part B, all patients were confirmed to be infected with <em>P. falciparum</em> at baseline. Except for one patient in Part B with a baseline parasite count of 399/µL, all patients (Part A and Part B) had a baseline parasite count of > 1000/µL.</p>\n<p>\n <strong>Efficacy results</strong>:</p>\n<ul>\n <li>\n <strong>Primary efficacy (by PPS)</strong>:</li>\n</ul>\n<ul>\n <li>\n The primary objective of Part A was met, and the null hypothesis was rejected for all KAF156/LUM‑SDF treatment groups. At Day 29, for the PCR‑corrected ACPR rate, the lower limit of 2-sided 95% exact CI was > 80% (pre-defined primary efficacy success criteria) for all KAF156/LUM‑SDF treatment groups.</li>\n <li>\n In Part B, only the KAF400 mg/LUM960 mg 3-day regimen met the success criteria of lower limit of 2-sided 95% exact CI being > 80% for ACPR rate (83.1%), whereas in the 1-day and 2-day regimens, the lower limit of 2-sided 95% CI was 62.7% and 79.2%, respectively.</li>\n <li>\n For the pooled analysis (Part A + Part B), the PCR-corrected ACPR rate at Day 29 for the KAF156/LUM-SDF treatment regimens was the highest in the 3-day regimen (96.4%), and this was numerically similar to Coartem (97.9%), with a treatment difference of −1.4% (95% CI: −7.2, 4.3). At Day 29, the 2-day regimen showed a PCR‑corrected ACPR rate of 94.7% and the 1-day regimen was lower at 84.7%.</li>\n <li>\n <u>Subgroup analysis</u>: Overall, for the KAF156/LUM‑SDF treatment regimens in the pooled analysis, the PCR‑corrected ACPR rate was homogenous and consistent across the subgroups (age group, baseline weight group, gender, and region), with a higher response rate in the 2-day and 3-day regimens compared to the 1-day regimen.</li>\n</ul>\n<ul>\n <li>\n For the KAF156/LUM-SDF regimens, the PCR-corrected ACPR rate in the 1-day regimen was lower in younger patients (< 18 years of age) compared to adults (≥ 18 years of age). Most patients with lower PCR‑corrected ACPR rates in Part A were < 18 years of age. Overall, for the KAF156/LUM‑SDF treatment regimens, lower response rates were observed in the younger patients who were < 12 years of age (78.9% to 100% in patients 2 to < 6 years; 74.2% to 96.3% in patients 6 to < 12 years).</li>\n</ul>\n<ul>\n <li>\n <u>Sensitivity analysis</u>: A sensitivity analyses was performed where PCR‑corrected ACPR rate was recalculated by excluding patients with reinfections prior to Day 29. Results from the sensitivity analysis were consistent with the primary analysis.</li>\n</ul>\n<ul>\n <li>\n <strong>Secondary efficacy</strong>:</li>\n</ul>\n<ul>\n <li>\n <strong>PCR-corrected ACPR rates by PPS</strong>:</li>\n</ul>\n<ul>\n <li>\n At Day 15, for the KAF156/LUM‑SDF treatment groups, the PCR‑corrected ACPR rate varied from 95.8% to 100% in Part A and from 97.8% to 100% in Part B. For the KAF156/LUM-SDF treatment groups in Part A, higher PCR‑corrected ACPR rates were noted in the 2-day and 3‑day regimens, and these were numerically similar to Coartem. In Part B, the highest PCR‑corrected ACPR rate was noted in the 3‑day regimen (100%), and this was numerically identical to Coartem (100%).</li>\n <li>\n At Day 43, the PCR‑corrected ACPR rate varied from 90% to 97.9% in Part A and from 75% to 92.5% in Part B. In Part A, for the KAF156/LUM-SDF treatment groups, higher PCR‑corrected ACPR rates were noted in the 2-day and 3-day regimens, and these were numerically similar to Coartem. In Part B, the highest PCR-corrected ACPR rate was noted in the 3-day regimen (92.5%), and this was numerically higher than Coartem (90.9%).</li>\n <li>\n For the pooled analysis (Part A + Part B), the PCR-corrected ACPR rate for the KAF156/LUM-SDF treatment regimens varied from 96.9% to 100% at Day 15 and 82.7% to 94% at Day 43. For Coartem, it was 100% at Day 15 and 93.6% at Day 43.</li>\n</ul>\n<ul>\n <li>\n <strong>Uncorrected ACPR rate by FAS</strong>:</li>\n</ul>\n<ul>\n <li>\n In Part A, the uncorrected ACPR rate was more than 80% for all KAF156/LUM‑SDF treatment groups at Days 15, 29, and 43, except for the 1‑day regimen of KAF800 mg/LUM960 mg at Day 29 (78.4%) and Day 43 (70.6%). Generally, the uncorrected ACPR rate was similar across the KAF156/LUM‑SDF treatment groups at Days 15, 29, and 43; however, there was a decline in the uncorrected ACPR rate at Day 43 due to recrudescence (11 patients) or reinfections (30 patients). For Coartem, the uncorrected ACPR rate at Days 15, 29, and 43 was 100%, 96.3%, and 70.4%, respectively.</li>\n <li>\n The uncorrected ACPR rate was lower in Part B compared to Part A, and sharply declined from Day 15 to Day 43 due to recrudescence (22 patients at Day 43) or reinfection (30 patients at Day 43). For Coartem, the uncorrected ACPR rate at Days 15, 29, and 43 was 100%, 62.5%, and 45.8%, respectively.</li>\n <li>\n For the pooled analysis, for the KAF156/LUM-SDF treatment regimens and Coartem, the uncorrected ACPR rate declined from Day 15 to Day 43. At Days 29 and 43, for KAF156/LUM-SDF, the 2-day and 3-day regimens showed a higher response rate compared to the 1-day regimen. At Day 43, the uncorrected ACPR rate in all the KAF156/LUM-SDF regimens was numerically higher than in the Coartem treatment group.</li>\n <li>\n <u>Subgroup analysis</u>: At Day 29, higher uncorrected ACPR rate in the KAF156/LUM‑SDF 2-day and 3-day regimens compared to the 1‑day regimen was seen in all the subgroups (age group, baseline weight group, gender, and region).</li>\n <li>\n <u>Sensitivity</u><u> analysis</u>: A sensitivity analysis for uncorrected ACPR at Day 29 was performed where patients receiving non‑study antimalarial drugs in the absence of treatment failure were considered as non‑responders. Results from the sensitivity analysis were consistent with the secondary analysis.</li>\n</ul>\n<ul>\n <li>\n <strong>Treatment failure by FAS</strong>:</li>\n</ul>\n<p>\n In both Part A and Part B:</p>\n<ul>\n <li>\n No patients were noted with early treatment failure.</li>\n <li>\n The proportion of patients with late clinical failure was numerically higher in the 1‑day regimen of KAF156/LUM-SDF and Coartem than the 3-day and 2‑day regimens of KAF156/LUM-SDF (with the exception of KAF400 mg/LUM480 mg – 3‑day regimen in Part A, in which 6.3% patients had late clinical failure, which was similar to the 1‑day regimens).</li>\n <li>\n The proportion of patients with late parasitological failure was numerically higher in the Coartem treatment group than in the KAF156/LUM-SDF treatment groups and regimens.</li>\n</ul>\n<ul>\n <li>\n <strong>Parasitemia by FAS</strong>: For Part A and Part B, the proportion of patients with parasitemia declined from 12 hours to 48 hours after treatment, with a sharp decline noted from 24 hours to 48 hours after treatment. The proportion of patients with parasitemia in the KAF156/LUM-SDF treatment groups was overall comparable with the Coartem treatment group.</li>\n</ul>\n<ul>\n <li>\n <strong>Reinfections and recrudescence</strong>: Overall, for Part A and Part B, the incidence rate of reinfections was higher than recrudescence in the KAF156/LUM-SDF treatment groups and Coartem group. Also, the overall rate of recrudescence was higher in Part B compared to Part A.</li>\n</ul>\n<ul>\n <li>\n <strong><u>Recrudescence</u></strong>:</li>\n</ul>\n<ul>\n <li>\n In Part A, for the KAF156/LUM-SDF treatment groups, recrudescence was noted in a total of 11 patients out of 310 patients: 4 patients in KAF400 mg/LUM960 mg (1‑day regimen), 3 patients in KAF800 mg/LUM960 mg (1‑day regimen), 1 patient in KAF400 mg/LUM960 mg (2‑day regimen), 1 patient in KAF200 mg/LUM480 mg (3‑day regimen), and 2 patients in KAF400 mg/LUM960 mg (3‑day regimen). Recrudescence events occurred up to Day 15 in 1 patient, between Day 15 and Day 29 in 8 patients, and between Day 29 and Day 43 in 2 patients. There were no patients with recrudescence events in the Coartem treatment group.</li>\n <li>\n In Part B, for the KAF156/LUM-SDF regimens, recrudescence was noted in a total of 22 out of 150 patients (12 patients in the 1-day regimen, 7 patients in the 2-day regimen, and 3 patients in the 3-day regimen). In KAF156/LUM‑SDF treatment groups, recrudescence events occurred up to Day 15 in 1 patient, between Day 15 and Day 29 in 13 patients, and between Day 29 and Day 43 in 8 patients. Recrudescence events were noted in 2 patients in the Coartem treatment group (between Day 15 and Day 29 in 1 patient and between Day 29 and Day 43 in 1 patient).</li>\n</ul>\n<ul>\n <li>\n <strong><u>Reinfection</u></strong>:</li>\n</ul>\n<ul>\n <li>\n In Part A, reinfections were noted in a total of 31 patients in the KAF156/LUM‑SDF treatment groups. Reinfections were noted in 10 patients, 4 patients, and 17 patients in the 1‑day, 2‑day, and 3‑day regimens, respectively. Reinfection events occurred between Day 15 and Day 29 in 9 patients, and between Day 29 and Day 43 in 22 patients; no events occurred before Day 15. Reinfection events were noted in 8 patients in the Coartem treatment group (between Day 15 and Day 29 in 1 patient and between Day 29 and Day 43 in 7 patients).</li>\n <li>\n In Part B, reinfections were noted in a total of 30 patients in the KAF156/LUM‑SDF treatment regimens (11 patients in the 1-day regimen, 10 patients in the 2-day regimen, and 9 patients in the 3-day regimen). Reinfection events were observed between Day 15 and Day 29 in 14 patients and between Day 29 and Day 43 in 16 patients; no events occurred before Day 15. Reinfection events were noted in 10 patients in the Coartem treatment group (between Day 15 and Day 29 in 6 patients and between Day 29 and Day 43 in 4 patients).</li>\n</ul>\n<ul>\n <li>\n <strong>Parasite clearance time by FAS</strong>:</li>\n</ul>\n<ul>\n <li>\n In Part A, the median parasite clearance time ranged from 36.2 hours to 48 hours for the KAF156/LUM-SDF treatment groups and was 36 hours for Coartem.</li>\n <li>\n In Part B, the median parasite clearance time in the KAF156/LUM-SDF 1‑day, 2‑day, 3‑day regimens was 36.8 hours, 48 hours, and 36.7 hours, respectively. It was 36 hours for patients treated with Coartem.</li>\n</ul>\n<p>\n <strong>Pharmacokinetic results:</strong></p>\n<ul>\n <li>\n <strong><u>PK Run‑in part</u></strong>:</li>\n</ul>\n<ul>\n <li>\n There was no increase in KAF156 exposure in the presence of lumefantrine.</li>\n</ul>\n<ul>\n <li>\n <strong><u>Part A</u></strong>:</li>\n</ul>\n<ul>\n <li>\n In general, AUC0-24h from sparse sampling was comparable to rich sampling for both KAF156 and lumefantrine. KAF156 exposures increased with dose, however, lumefantrine exposures appeared to be under dose proportional.</li>\n <li>\n The half‑life geo‑mean, based on rich PK sampling, ranged from 23.7 hours to 33.1 hours for KAF156 and 30.9 hours to 80.9 hours for lumefantrine.</li>\n</ul>\n<ul>\n <li>\n <strong><u>Part A and Part B</u></strong>: For both KAF156 and lumefantrine:</li>\n</ul>\n<ul>\n <li>\n Comparable exposures (Cmax and AUC0-24h) were noted for Part A and Part B. The C168h for KAF156 was lower in Part B compared to Part A.</li>\n <li>\n There was no difference noted in exposures (Cmax and AUC0‑24h) across similar body weight groups and age‑groups.</li>\n <li>\n A decreasing trend of C168h was noted in the lower weight groups and lower age‑groups for KAF156.</li>\n</ul>\n<p>\n <strong>Safety results</strong>:</p>\n<ul>\n <li>\n The most common AEs across the KAF156/LUM-SDF treatment groups and regimens included malaria, upper respiratory tract infection, headache, pyrexia, vomiting, abdominal pain, electrocardiogram QT prolonged, and blood bilirubin increased.</li>\n</ul>\n<ul>\n <li>\n In Part A, the proportion of patients with AEs were similar across all KAF156/LUM‑SDF regimens (in the range of 64.7% to 78.8%) and the Coartem treatment group (70.4%). The incidence of individual AEs did not show any specific trends across the KAF156/LUM-SDF and Coartem treatment groups; however, the incidence of vomiting was higher in the KAF800 mg/LUM 960 mg (1‑day regimen) (8 patients, 15.7%) compared to all other KAF156/LUM-SDF treatment groups and Coartem. Additionally, the AEs of malaria (which were due to reappearance of the parasite), pyrexia, and treatment failure had a higher incidence in the Coartem treatment group than the KAF156/LUM-SDF treatment groups.</li>\n <li>\n In Part B, the proportion of patients with AEs in the KAF156/LUM-SDF treatment regimens was in the range of 71.1% to 77.4%, and was 58.3% for the Coartem treatment group. The AEs of malaria, pyrexia, blood bilirubin increased, and blood alkaline phosphatase increased had a higher incidence in the Coartem treatment group compared to the KAF156/LUM-SDF treatment regimens.</li>\n <li>\n Overall, for Part A and Part B, the incidence of AEs was consistent across age‑groups, with the exception of a few AEs that showed age‑specific differences. The AEs with a higher incidence in pediatric populations (< 12 years) compared to adolescents and adults included vomiting, pyrexia, and malaria. The AEs with a higher incidence in adolescents and adults compared to pediatric populations included electrocardiogram QT prolonged and headache.</li>\n <li>\n There were no meaningful differences in the safety profile of KAF156/LUM-SDF treatment regimens and Coartem across the subgroups of age, baseline weight, and gender.</li>\n</ul>\n<ul>\n <li>\n Most of the AEs in the KAF156/LUM-SDF treatment groups and all AEs in the Coartem treatment group were of low grade (grade 1-2) severity.</li>\n <li>\n Proportion of patients with AEs suspected to be related to the study treatment:</li>\n</ul>\n<ul>\n <li>\n In Part A, it ranged from 25.5% to 47.1% in the KAF156/LUM-SDF treatment groups, and was 25.9% in the Coartem treatment group.</li>\n <li>\n In Part B, it was 13.5%, 22.6%, 15.6%, and 8.3% in the KAF156/LUM-SDF 1‑day, 2‑day, 3‑day regimens, and Coartem, respectively.</li>\n</ul>\n<ul>\n <li>\n No patients died during the study.</li>\n <li>\n Across all treatment groups, SAEs were noted in 9 patients in Part A and 12 patients in Part B (mainly single cases in 1 patient each). Most of the SAEs were grade 1-2 laboratory abnormalities that were reported based on protocol‑defined laboratory thresholds.</li>\n</ul>\n<ul>\n <li>\n For Part A and Part B, across the treatment groups, a higher proportion of SAEs was noted in the age-group of 2 to < 6 years (13.3% to 18.2% in the KAF156/LUM‑SDF treatment regimens, and 20% in the Coartem treatment group) compared to the older age groups. There was no difference in the incidence of SAEs with respect to gender.</li>\n</ul>\n<ul>\n <li>\n Overall, 8 patients discontinued the study treatment due to the AE of vomiting (Part A: 1 patient in the KAF400 mg/LUM960 mg – 3‑day regimen; Part B: 2 patients each in the 1‑day and 3‑day regimens and 3 patients in the 2‑day regimen). Discontinuations due to AE were after the Day 1 dose of KAF156/LUM‑SDF in 7 patients and after the Day 2 dose of KAF156/LUM‑SDF in 1 patient.</li>\n <li>\n In Part A and Part B, there were no AEs leading to interruption of the study treatment.</li>\n <li>\n The adverse events of special interest for KAF156/LUM-SDF included events related to bradycardia, gastrointestinal tolerability, hematological disorders, hepatotoxicity, QTc prolongation, and thyroid hypertrophy and hyperplasia.</li>\n</ul>\n<ul>\n <li>\n In Part A, events related to gastrointestinal tolerability were noted in fewer patients treated with Coartem (7.4%) compared to KAF156/LUM-SDF (11.1% to 25.5%). The proportion of patients with hematological disorders was comparable between KAF156/LUM-SDF treatment groups (5.6% to 15.7%) and Coartem (11.1%). The incidence of QTc prolongation was comparable across the KAF156/LUM-SDF treatment groups (9.6% to 17.6%) and Coartem (11.1%). Events potentially indicative of bradycardia were noted only in the KAF156/LUM‑SDF treatment group and ranged from 2% to 9.8%. Events potentially indicative of hepatotoxicity were noted in fewer patients treated with KAF156/LUM‑SDF (1.9% to 7.8%) compared to Coartem (11.1%). Events potentially indicative of thyroid hypertrophy and hyperplasia were reported only in 1 patient in the KAF400 mg/LUM960 mg – 3‑day regimen.</li>\n <li>\n In Part B, events related to gastrointestinal tolerability were noted in the KAF156/LUM-SDF regimens (1-day: 13.5%, 2-day: 15.1%; 3‑day: 15.6%). The proportion of patients with hematological disorders was < 10% in the KAF156/LUM‑SDF treatment regimens (1‑day: 9.6%; 2‑day: 7.5%; 3‑day: 6.7%). Events potentially indicative of potential hepatotoxicity were noted in 5.8%, 7.5%, and 2.2% in the 1‑day, 2‑day, and 3‑day KAF156/LUM‑SDF treatment regimens, respectively. Events potentially indicative of QTc prolongation were reported only in the 2‑day (1 patient, 1.9%) and 3‑day (4 patients, 8.9%) KAF156/LUM-SDF treatment regimens. No AEs indicative of bradycardia and thyroid hypertrophy and hyperplasia was reported in the KAF156/LUM-SDF treatment groups.</li>\n</ul>\n<ul>\n <li>\n For Part A and Part B (KAF156/LUM-SDF and Coartem groups), generally no clinically meaningful change from baseline until Day 29 or Day 43 was noted for hemoglobin, platelets, and white blood cells.</li>\n <li>\n For Part A and Part B, for KAF156/LUM-SDF and Coartem groups no clinically meaningful change from baseline until Day 29 or Day 43 was noted for creatinine (serum/plasma), aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin, total bilirubin, alkaline phosphatase, thyrotropin, and free thyroxine.</li>\n</ul>\n<ul>\n <li>\n For Part A and Part B, isolated elevations in AST/ALT and total bilirubin were noted in a few patients; however, there was no concurrent increases in these parameters, and no cases of Hy’s Law were reported. Of note, in Part B, the proportion of patients with newly occurring liver enzyme abnormalities during the study were higher in the Coartem treatment group (21 patients) compared to the KAF156/LUM‑SDF treatment groups (17 patients).</li>\n</ul>\n<ul>\n <li>\n In Part A, there were no clinically significant changes in urine parameters post‑baseline, except for urine protein. The proportion of patients with proteinuria declined at Day 29 and Day 43 compared to baseline. In Part B, no clinically significant changes in urine parameters were noted post‑baseline.</li>\n <li>\n No significant changes in vital signs were noted in adults (≥ 18 years). However, in patients < 18 years of age (in both Part A and Part B), the frequently reported notable vital signs included high pulse rate, low blood pressure (both systolic and diastolic blood pressure), and high axillary body temperature (≥ 37.5°C). An increase in body weight (> 7% from baseline) was noted in 18 patients in Part A (the AE of weight increased noted in 2 patients in Part A) and in 26 patients in Part B.</li>\n <li>\n In both, Part A and Part B, most frequently, new QTcF values noted were > 450 ms and ≤ 480 ms; QTcF > 480 ms occurred in only 1 patient in Part A (KAF400 mg/LUM480 mg - 3-day regimen), and none of the patients had QTcF > 500 ms. The majority of changes in QTcF from baseline were ≥ 30 ms and < 60 ms; however, in a few patients, changes in QTcF from baseline ≥ 60 ms were also noted. None of the QT changes were symptomatic.</li>\n</ul>\n<ul>\n <li>\n In Part A, the overall frequency of QTcF increase from baseline ≥ 30 ms to < 60 ms was comparable between the KAF156/LUM-SDF treatment groups (33.3% to 48.1%) and Coartem (40.7%), while the proportion of patients with QTcF increase from baseline ≥ 60 ms was generally higher in the KAF156/LUM-SDF groups (3.9% to 13.7%) than in the Coartem treatment group (3.7%), without apparent dose dependency.</li>\n <li>\n In Part B, the frequency of QTcF increase from baseline ≥ 30 ms to < 60 ms was comparable between the KAF156/LUM-SDF treatment regimens (15.4% to 46.7%) and Coartem (25%), and was slightly higher in the KAF156/LUM-SDF 3-day regimen (46.7%). The proportion of patients with QTcF increase from baseline ≥ 60 ms was generally higher in the KAF156/LUM‑SDF treatment regimens (1.9% to 13.3%) compared to Coartem (0), with an apparent dose proportionality.</li>\n</ul>\n<p>\n <strong>Conclusion</strong>:</p>\n<p>\n This was the first study to evaluate KAF156/LUM-SDF in patients with uncomplicated <em>P. falciparum</em> malaria in Africa and Asia. No clinically significant PK interaction between KAF156 and LUM-SDF was observed. The efficacy and safety data in children (≥ 2 years), adolescents and adults (≥ 12 years) show that KAF156/LUM-SDF is effective and well‑tolerated. There was no impact on outcome of parasite resistance markers present at baseline (exploratory resistance markers analysis will be reported separately as data were not available at the time of database lock).</p>\n<p>\n Overall, the positive benefit-risk balance supports the evaluation of the identified effective and safe dose range of KAF156/LUM-SDF in future Phase III studies. KAF156 when given in combination with LUM‑SDF to patients with uncomplicated malaria could cover the unmet medical need for antimalarial treatment with a new mechanism of action to counter the emergence of resistance to artemisinin.</p>\n<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:100.0%;\" width=\"100%\">\n <thead>\n <tr>\n <th colspan=\"4\" style=\"width:100.0%;\">\n <p>\n History of changes to the synopsis</p>\n </th>\n </tr>\n <tr>\n <th style=\"width:9.86%;\">\n <p>\n Version</p>\n </th>\n <th style=\"width:18.2%;\">\n <p>\n Date<br />\n (content final)</p>\n </th>\n <th style=\"width:54.66%;\">\n <p>\n Summary of Changes</p>\n </th>\n <th style=\"width:17.28%;\">\n <p>\n Change to overall conclusion</p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:9.86%;\">\n <p>\n 1.0</p>\n </td>\n <td style=\"width:18.2%;\">\n <p>\n 07-Dec-2021</p>\n </td>\n <td style=\"width:54.66%;\">\n <p>\n Original version</p>\n </td>\n <td style=\"width:17.28%;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n KAF156 (ganaplacide) belongs to a novel class of antimalarials, imidazolopiperazines, and is active against a broad range of Plasmodium species, including parasites resistant against current drugs. The compound is cidal in vivo against both blood and liver stages of the parasite. It has also shown gametocytocidal activity, which might offer the opportunity for <em>transmission blocking</em>. The mechanism of action is likely based on inhibition of parasite protein trafficking, blocking the establishment of new</p>\n<p>\n KAF156 is combined with the new Lumefantrine solid dispersion formulation (LUM-SDF) in a fixed-dose regimen. LUM-SDF has improved bioavailability as compared to the conventional formulation of lumefantrine, leading to a reduced dosing frequency which could <em>improve patient compliance</em>.</p>\n<p>\n Such fixed-dose combination of 2 anti-malarial drugs strongly reduces the chance of resistance development; this is a standard practice as per WHO guidelines on current antimalarial therapy and the development of new anti-malarials.</p>\n<p>\n KAF156/LUM-SDF is the first combination treatment that does not contain an artemisinin derivative. This makes it an important asset in the fight against emerging resistance of malaria parasites to Artemisinin-based Combination Treatments (ACTs). Resistance of the P. falciparum against artemisinin emerged in Asia and more recently in sub-Saharan Africa (SSA). This resistance leads initially to slower parasite clearance, but also places more pressure on the long-acting ACT partner compound. This may eventually lead to complete treatment failure.</p>\n<p>\n Whereas this new drug combination is still in clinical development stage, the results of this study encourage the sponsor to continue development and launch this new non-ACT treatment as soon as possible in patients of 6 months and older, with particular focus on P. falciparum infections in SSA which constitutes the major part of global malaria burden.</p>\n
      • quantity_imported2325 Tablets+186 Sachets+360 Sachets+156 Tablets+270 Tablets
      • quantity_dispensed457 Tablets+117 Sachets+186 Sachets+12 Tablets+78 Tablets
      • quantity_destroyed1868 Tablets+69 Sachets+174 Sachets+144 Tablets+192 Tablets
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2025-02-27 16:54:09
      • created2018-05-26 20:29:29
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    • InvestigatorContact(array)
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        • family_nameOgutu
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        • professional_addressP.O BOX 40100
        • telephone+254 733 966065 or +254 733 333 530
        • emailbernhards.ogutu@usamru-k.org
        • created2018-05-26 20:47:04
        • modified2021-04-22 11:53:35
    • SiteDetail(array)
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        • contact_personDr Kariuki
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        • created2018-05-26 20:47:04
        • modified2021-04-22 11:53:35
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          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
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        • site_nameWalter Reed Project
        • physical_addressOff Kisumu-Bondo Road,Opposite Kombewa Sub county Hospital
        • contact_details Physical address: P.O Box 54-40100, Kisumu, Kenya
        • contact_personDr Bernhards Ogutu
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        • created2018-05-26 21:57:36
        • modified2021-04-22 11:53:35
        • County(array)
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          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id343
        • application_id679
        • sponsorNOVATIS
        • sponsor_typeIndustry
        • contact_personMICHELLE BOTHA
        • address1011 Pretorius avenue South Lyttleton Manor, Centurion South Africa
        • telephone_number+27 (0)82 8888 132
        • fax_number+27 (0)12 671 2389
        • cell_number+27 (0)12 671 2334
        • email_addressmichelle.botha@iqvia.com
        • created2018-05-26 20:47:04
        • modified2021-04-22 11:53:35
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App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

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      • 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