Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202205899641128 Date of Approval: 30/05/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Anti-malaria Monoclonal Antibody for Malaria Prevention in Kenyan children
Official scientific title Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium falciparum, in an Age De-Escalation, Dose-Escalation Trial and a Randomized, Placebo-Controlled, Double-Blind Trial of Children in Western Kenya
Brief summary describing the background and objectives of the trial The purpose of this study is to evaluate the safety and tolerability of one-time subcutaneous (SC) administration of monoclonal antibody (MAb) L9LS in healthy Kenyan children aged 5 months to 10 years, as well as the protective efficacy of one or two doses of L9LS against naturally occurring Plasmodium falciparum (Pf) infection among Kenyan children aged 5 to 59 months at enrollment, in a setting of perennial high transmission.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) L9LSKenya
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 15/08/2022
Actual trial start date
Anticipated date of last follow up 29/02/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 396
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
4413 Kenya Medical Research Institute Scientific and Ethics Review Unit
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group L9LS Arm1 Part 1 5mg/kg once 5 mg/kg of L9LS via SC injection to children 5-10 years old 9
Experimental Group L9LS Arm2 Part 1 10 mg/kg Once 10 mg/kg of L9LS via SC injection among children age 5-10 9
Experimental Group L9LS Arm3 Part 1 20 mg/kg once 20 mg/kg of L9LS Children age 5-10 years 9
Experimental Group L9LS Arm4 Part 1 5 mg/kg once 5 mg/kg Children 5-59 months 9
Experimental Group L9LS Arm5 Part 1 10 mg/kg once 10 mg/kg L9LS children 5-59 months 9
Experimental Group L9LS Arm6 Part 1 20 mg/kg once 20mg/kg L9LS to children 5-59 months 9
Control Group Placebo Part 1 children 5 to 10 years Normal saline placebo once Normal saline placebo subcutaneously to children 5-10 years 9 Placebo
Control Group Placebo Part 1 children 5 to 59 months Normal saline placebo once Normal saline placebo children 5-59 months 9 Placebo
Experimental Group L9LS Part 2 Arm 1 10-19mg/kg once Subjects age 5-17 months will receive 1 dose of L9LS via SC injection and a dose of placebo 6 months later 54
Experimental Group L9LS Part 2 Arm 2 10-19mg/kg twice, 6 months apart Subjects age 5-17 months will receive 1 dose of L9LS and a second dose at 6 months via SC injection. 54
Control Group Placebo Part 2 children 5 to 17 months Normal saline placebo twice 6 months apart Subjects age 5-17 months will receive 2 doses of placebo via SC injection 6 months apart. 54 Placebo
Experimental Group L9LS Part 2 Arm 3 10-19mg/kg once Subjects age 18-59 months will receive 1 dose of L9LS and a placebo dose at 6 months via SC injection. 54
Experimental Group L9LS Part 2 Arm 4 10-19mg/kg twice 6 months apart Subjects age 18-59 months will receive 1 dose of L9LS and a second dose at 6 months via SC injection. 54
Control Group Placebo Part 2 children 18 to 59 months twice two doses 6 months apart Normal saline placebo given subcutaneously twice, 6 months apart, to children age 18-59 months 54 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Healthy children aged 5 months to 10 years (Part 1) or 5-59 months (Part 2). 2. Weight ≥5 kg and weight ≤30 kg (Part 1) or weight ≥5 kg and ≤22.5 kg (Part 2). 3. Hemoglobin level ≥8 g/dL. 4. Height and weight Z-scores >-2. 5. Living within Alego-Usonga sub-county. 6. Able to participate for the duration of the trial. 7. Parent and/or guardian of participant able to provide informed consent. 1. Taking long-term cotrimoxazole. 2. Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit or receipt of an investigational product within the past 30 days. 4. Participation in part 1 of this study (for individuals being screened for enrollment into part 2) 5. Age < 12 months at the time the RTS,S/AS01 vaccine is anticipated to become available in the whole of Siaya County 6. Current significant medical condition (neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, authoimmune, renal, oncologic, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination. 7. Any history of menses. 8. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol. 9. Parental/guardian study comprehension examination score of <80% correct or per investigator discretion. 10. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration. 11. Known allergies or contraindication to dihydroartemisinin-piperaquine. 12. Use or known need at the time of enrolment (DP administration) for concomitant prohibited medication. 13. Increased risk of salivary gland hypofunction (dryness of the mouth, swelling under the tongue and/or below the ear, halitosis) 14. History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject’s participation in the protocol or compromise the scientific objectives, or other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or render the subject unable to comply with the protocol. Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 5 Month(s) 10 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/04/2022 Kenya Medical Research Institute Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Unnamed Road Kisumu 40100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Incidence and severity of local and systemic adverse events (AEs) occurring within 7 days after the administration of L9LS, and incidence of serious adverse events (SAEs) throughout the study period. Age de-escalation and dose-escalation study Measured through Month 3
Primary Outcome Incidence and severity of local and systemic adverse events (AEs) occurring within 7 days after the administration of L9LS, and incidence of serious adverse events (SAEs) throughout the study period. Efficacy study Measured through duration of the study- 52 weeks
Primary Outcome Pf blood-stage infection as detected by microscopic examination of thick blood smear for 52 weeks after administration of two doses of L9LS or placebo. Efficacy study Measured through week 52
Secondary Outcome Pf blood-stage infection as detected by microscopic examination of thick blood smear after administration of one dose of L9LS or placebo. Age de-escalation, dose-escalation and efficacy study Measured through 12 and 24 weeks after drug or placebo administration
Secondary Outcome Pf blood-stage infection as detected by microscopic examination of thick blood smear diagnosed by blood smear microscopy after administration of one dose of L9LS or placebo. Age de-escalation, dose-escalation and efficacy study Measured for 52 weeks after drug or placebo administration
Secondary Outcome Pf blood-stage infection as detected by RT-PCR of L9LS or placebo. Age de-escalation, dose-escalation and efficacy study Measured at 24 and 52 weeks after drug or placebo administration
Secondary Outcome Incidence of clinical malaria: an illness accompanied by measured fever ≥37.5°C in the previous 24 hours and Pf asexual parasitemia >5,000 parasites/μL as detected from microscopic examination of thick blood smear. Age de-escalation, dose-escalation and efficacy study Measured at 24 and 52 weeks after drug or placebo administration
Secondary Outcome Incidence of clinical malaria: fever ≥37.5°C, history of fever in the previous 24 hours accompanied by any level of Pf asexual parasitemia, detected from microscopic examination of thick blood smear, requires administration of anti-malarial treatment. Age de-escalation, dose-escalation and efficacy study Measured at 24 and 52 weeks after drug or placebo administration
Secondary Outcome Measurement of L9LS in sera of recipients (parts 1 and 2). Part 1: Day -14, Day 7, Day 28, Day 84 Part 2: Day -14, Day 56, Day 196, Day 336
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Siaya County Referral Hospital Hospital Road Siaya Township Alego Usonga Kenya
Kogelo Dispensary for part 2 Kogelo Road Siaya Township Alego Usonga Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation PO Box 23350 Seattle United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor National Institutes of Health 9000 Rockville Pike Bethesda United States of America Government
COLLABORATORS
Name Street address City Postal code Country
Centers for Disease Control and Prevention 1600 Clifton Rd Atlanta 30329 United States of America
Liverpool School of Tropical Medicine and Hygiene Pembroke Place Liverpool Liverpool L3 5QA United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Laura Steinhardt iyp6@cdc.gov +255677680008 2448 Barack Obama Dr
City Postal code Country Position/Affiliation
Dar es Salaam United Republic of Tanzania CDC
Role Name Email Phone Street address
Principal Investigator Titus Kwambai qbb5@cdc.gov 254722207281 KEMRI
City Postal code Country Position/Affiliation
Kisumu Kenya CDC
Role Name Email Phone Street address
Public Enquiries Titus Kwambai qbb5@cdc.gov 254722207281 KEMRI
City Postal code Country Position/Affiliation
Kisumu Kenya CDC
Role Name Email Phone Street address
Scientific Enquiries Laura Steinhardt LSteinhardt@cdc.gov 255677680008 2448 Barack Obama Dr
City Postal code Country Position/Affiliation
Dar es Salaam United Republic of Tanzania CDC
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Deidentified data including demographics and outcomes Study Protocol Within 12 months of study completion Controlled data access will be provided upon reasonable request following all applicable Kenyan rules and regulations. To obtain data access, a written request must be sent to the PI detailing the purpose and plan for the data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information