Anti-malaria MAb in Kenyan Children | NCT05400655

NCT05400655

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Centers for Disease Control and Prevention	FED
National Institutes of Health (NIH)	NIH
Kenya Medical Research Institute	OTHER
Liverpool School of Tropical Medicine

Description Module

Detailed Description

A two-part, phase 2 trial evaluating 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.

Part 1 includes part 1a and part 1b and is an age de-escalation and dose-escalation study. In part 1a, in a stepwise fashion, children aged 5-10 years will receive 5 mg/kg of L9LS or placebo and be followed for 3 months to assess tolerability and safety. If acceptable tolerability and safety profiles are met at 1-week post-injection, the 5 mg/kg dose of L9LS or placebo will be administered to children aged 5-59 months while enrolling another cohort of children aged 5-10 years at a dose of 10 mg/kg of L9LS or placebo. If after 1 week, the 10 mg/kg dose is found to be safe in children aged 5-10 years and the 5 mg/kg dose is found to be safe in children aged 5-59 months, a 20 mg/kg dose of L9LS or placebo will be administered to children aged 5-10 years and a 10 mg/kg dose of L9LS or placebo to children aged 5-59 months. Finally, if these doses are found safe after 1 week, a 20 mg/kg dose of L9LS or placebo will be administered to children aged 5-59 months. Should tolerability and safety of all doses be acceptable in children aged 5-59 months, part 2 of the trial will begin. Part 1b of the study was added later and will include two additional dose escalation cohorts of children aged 5 to 71 months and will test 30 mg/kg L9LS and 40 mg/kg L9LS. Dosing in part 1 of the study will be weight-based and all doses will be administered SC in a double-blinded fashion. 12 participants in each age-dose group will be enrolled in a 3:1 ratio of L9LS to placebo, and all participants will be followed for a total of 3 months.

Part 2 is the efficacy study. Children 5-59 months of age will be randomized to receive a 10-20 mg/kg dose of L9LS or placebo by SC administration. There will be two L9LS cohorts, one 5-17 months of age and another 18-59 months of age, which will constitute one L9LS arm. A placebo arm will be composed of children 5-59 months of age. They will be followed over 12 months with monthly blood smear microscopy and polymerase chain reaction (PCR) and twice-monthly symptomatology and careseeking behavior questionnaires. Dosing will be based on three weight bands; all doses will be administered SC with fixed doses of 75 mg L9LS, 150 mg L9LS, or 225 Mg L9LS, resulting in a range of 10-20 mg/kg in a double-blinded fashion. Blood will be drawn to assess antibody titers at baseline, and at three additional time points over 12 months to establish pharmacokinetics (PK). Participants in the L9LS arm will be randomized 1:1 at baseline to receive either a second L9LS injection or a placebo injection to evaluate the additional efficacy of a second dose administered 6 months after the first dose. (Those in the placebo arm will receive a second injection of placebo.) Participants will be followed for an additional 6 months after the second injection with monthly blood smear microscopy and PCR, and a blood draw at month 11 to assess L9LS PK.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Age de-escalation and dose-escalation study: Arm 1a: Age 5-10 years, 5 mg/kg of L9LS	Experimental	Healthy children aged 5-10 years receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2.	Drug: L9LS
Age de-escalation and dose-escalation study: Arm 1b: Age 5-10 years, Placebo	Placebo Comparator	Healthy children aged 5-10 years receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2.	Other: Placebo
Age de-escalation and dose-escalation study: Arm 2a: Age 5-59 months, 5 mg/kg of L9LS	Experimental	Healthy children aged 5-59 months receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3.	Drug: L9LS
Age de-escalation and dose-escalation study: Arm 2b: Age 5-59 months, Placebo	Placebo Comparator	Healthy children aged 5-59 months receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3.	Other: Placebo
Age de-escalation and dose-escalation study: Arm 2c: Age 5-10 years, 10 mg/kg of L9LS

Interventions

Name	Type	Description	Arm Group Labels	Other Names
L9LS	Drug	Administered subcutaneously.	Age de-escalation and dose-escalation study: Arm 1a: Age 5-10 years, 5 mg/kg of L9LS Age de-escalation and dose-escalation study: Arm 2a: Age 5-59 months, 5 mg/kg of L9LS

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Local Adverse Events (AEs)	Number of participants with at least one solicited local adverse events occurring within seven days of administration of intervention. Local reactogenicity included injection site pain, tenderness, bruising, swelling, redness, induration, pruritus, and other (e.g. injection site reaction). Adverse events were captured by Investigator examination and history from participants.	Age De-escalation and Dose escalation: within 7 days of administration of intervention; Efficacy study: within 7 days after first intervention, and 7 days after second intervention (second intervention occurred 6 months post first intervention)
Number of Participants With Local Adverse Events (AEs) (by Grade)	The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity. Grade 2: Pain = Repeated use of non-narcotic pain reliever > 24 hours or interferes with daily activity; Tenderness= Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity. Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = > 10 cm; Induration/Swelling = > 10 cm or prevents daily activity. Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis Grade 5: Death	Age De-escalation and Dose escalation: within 7 days of administration of intervention; Efficacy study: within 7 days after first intervention, and 7 days after second intervention (second intervention occurred 6 months post first intervention)
Number of Participants With Systemic Adverse Events (AEs)	Number of participants with local adverse events occurring within seven days of administration of intervention. Systemic reactogenicity events included pyrexia (fever), malaise (feeling unusually tired or unwell), muscle aches, headache, chills, nausea, and joint pain. Adverse events were captured by Investigator examination and history from participants.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Healthy children aged 5 months to 10 years (Part 1) or 5-59 months (Part 2). Weight ≥5 kg and weight ≤30 kg (Part 1) or weight ≥5 kg and ≤22.5 kg (Part 2) or weight ≥5 kg and ≤20 kg (for 30 mg/kg group) or weight ≥5 kg and ≤15 kg (for 40 mg/kg group), to ensure a maximum volume of two 2-mL (Part 1b) Hemoglobin level ≥8 g/dL. Height and weight Z-scores >-2. Living within Alego-Usonga sub-county. Able to participate for the duration of the trial. Parent and/or guardian of participant able to provide informed consent.

Exclusion Criteria

Individuals meeting any of the following criteria will be excluded from study participation:

Taking long-term cotrimoxazole. Participation or planned participation in any other interventional trial with an investigational product prior to the last required protocol visit or receipt of an investigational product within the past 30 days. (Note: Past, current, or planned participation in observational studies is NOT exclusionary.) Received any doses of any malaria vaccine. Participation in part 1 of this study (for individuals being screened for enrollment into part 2) Age < 12 months at the time the RTS,S/AS01 vaccine is anticipated to become available in the whole of Siaya County Current significant medical condition (neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, renal, oncologic, or hematological) or evidence of any serious underlying medical condition identified by medical history, physical examination, or laboratory examination.

Known sickle cell disease. (Note: Known sickle cell trait is NOT exclusionary.) White blood cell, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. Subjects may be included at the investigator's discretion for values that are not clinically significant (ie., do not require any repeat or follow-up).

Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Subjects may be included at the investigator's discretion for values that are not clinically significant.) Infected with HIV. History of a severe allergic reaction or anaphylaxis. Severe asthma (defined as asthma that is unstable or required emergency care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years).

Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.

Known immunodeficiency syndrome. Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day 0.

Known asplenia or functional asplenia. Clinical signs of malnutrition. Receipt of immunoglobulins and/or blood products within the past 6 months. Any history of menses. 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.

Parental/guardian study comprehension examination score of <80% correct or per investigator discretion.

Receipt of a live vaccine or a killed vaccine within the past 2 weeks prior to study agent administration.

Known allergies or contraindication to dihydroartemisinin-piperaquine.

Use or known need at the time of pre-enrolment (DP administration) of concomitant prohibited medication, including:

Antimicrobial agents of the following classes (systemic use only):

Macrolides (e.g. erythromycin, clarithromycin, azithromycin, roxithromycin) Fluoroquinolones (e.g., levofloxacin, moxifloxacin, sparfloxacin) Pentamidine Antiarrhythmic agents (e.g. amiodarone, sotalol) Antihistamines (e.g. promethazine) Antifungals (systemic): ketoconazole, fluconazole, itraconazole Antiretrovirals: Saquinavir Diuretics (e.g. hydrochlorothiazide, furosemide) Antipsychotics (neuroleptics): haloperidol, thioridazine Antidepressants: imipramine, citalopram, escitalopram Antiemetics: domperidone, chlorpromazine, ondansetron Increased risk of salivary gland hypofunction (dryness of the mouth, swelling under the tongue and/or below the ear, halitosis) 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.

Name	Affiliation	Role
Titus Kwambai, MD, PhD	Centers for Disease Control and Prevention	Principal Investigator
Laura Steinhardt, PhD, MPH	Centers for Disease Control and Prevention	Principal Investigator
Peter D Crompton, MD, MPH	National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)	Principal Investigator

PubMed Identifier	Type	Citation	Retractions
42035777	Derived	Steinhardt LC, Kwambai TK, Oneko M, Ouma E, Njoroge R, Callier V, Hu Z, Gutman JR, Yego R, Otieno K, Onoka K, Otieno L, Oduol K, Serebryannyy L, Lin BC, Adams W, Hickman S, Preston AC, Carlton K, Holdsworth M, Xiao Y, O Ter Kuile F, Odongo W, Murphy SC, Tran TM, Kariuki S, Crompton PD, Seder RA; Kenya Malaria mAb Trials Team. Safety and efficacy of the monoclonal antibody L9LS for malaria prevention in children exposed to perennial malaria transmission in Kenya: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2026 Apr 25;407(10539):1614-1625. doi: 10.1016/S0140-6736(26)00258-8.

Arm/Group Information

ID	Title	Description
FG000	Age De-escalation and Dose-escalation Study: Arm 1a: Age 5-10 Years, 5 mg/kg of L9LS	Healthy children aged 5-10 years receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2. L9LS: Administered subcutaneously.
FG001	Age De-escalation and Dose-escalation Study: Arm 1b: Age 5-10 Years, Placebo	Healthy children aged 5-10 years receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2. Placebo: Normal saline administered subcutaneously.
FG002	Age De-escalation and Dose-escalation Study: Arm 2a: Age 5-59 Months, 5 mg/kg of L9LS	Healthy children aged 5-59 months receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3. L9LS: Administered subcutaneously.
FG003	Age De-escalation and Dose-escalation Study: Arm 2b: Age 5-59 Months, Placebo	Healthy children aged 5-59 months receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3. Placebo: Normal saline administered subcutaneously.
FG004	Age De-escalation and Dose-escalation Study: Arm 2c: Age 5-10 Years, 10 mg/kg of L9LS	Healthy children aged 5-10 years receive a single dose of 10 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3. L9LS: Administered subcutaneously.
FG005	Age De-escalation and Dose-escalation Study: Arm 2d: Age 5-10 Years, Placebo	Healthy children aged 5-10 years receive a single dose placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 3. Placebo: Normal saline administered subcutaneously.
FG006	Age De-escalation and Dose-escalation Study: Arm 3a: Age 5-10 Years, 20 mg/kg of L9LS	Healthy children aged 5-10 years receive a single dose of 20 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 4. L9LS: Administered subcutaneously.
FG007	Age De-escalation and Dose-escalation Study: Arm 3b: Age 5-10 Years, Placebo	Healthy children aged 5-10 years receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 4. Placebo: Normal saline administered subcutaneously.
FG008	Age De-escalation and Dose-escalation Study: Arm 3c: Age 5-59 Months, 10 mg/kg of L9LS	Healthy children aged 5-59 months receive a single dose of 10 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 4. L9LS: Administered subcutaneously.
FG009	Age De-escalation and Dose-escalation Study: Arm 3d: Age 5-59 Months, Placebo	Healthy children aged 5-59 months receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 4. Placebo: Normal saline administered subcutaneously.
FG010	Age De-escalation and Dose-escalation Study: Arm 4a: Age 5-59 Months, 20 mg/kg of L9LS	Healthy children aged 5-59 months receive a single dose of 20 mg/kg of L9LS one-time via subcutaneous administration. L9LS: Administered subcutaneously.
FG011	Age De-escalation and Dose-escalation Study: Arm 4b: Age 5-59 Months, Placebo	Healthy children aged 5-59 months receive a single dose of placebo via subcutaneous administration. Placebo: Normal saline administered subcutaneously.
FG012	Age De-escalation and Dose-escalation Study: Arm 5a: Age 5-71 Months, 30 mg/kg of L9LS	Healthy children aged 5-71 months receive a single dose of 30 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 6. L9LS: Administered subcutaneously.
FG013	Age De-escalation and Dose-escalation Study: Arm 5b: Age 5-71 Months, Placebo	Healthy children aged 5-71 months receive a single dose of placebo via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 6. Placebo: Normal saline administered subcutaneously.
FG014	Age De-escalation and Dose-escalation Study: Arm 6a: Age 5-71 Months, 40 mg/kg of L9LS	Healthy children aged 5-71 months receive a single dose of 40 mg/kg L9LS via subcutaneous administration. L9LS: Administered subcutaneously.
FG015	Age De-escalation and Dose-escalation Study: Arm 6b: Age 5-71 Months, Placebo	Healthy children aged 5-71 months receive a single dose of placebo via subcutaneous administration. Placebo: Normal saline administered subcutaneously.
FG016	Efficacy Study: Arm 1a: Age 5-17 Months, 10-20 mg/kg of L9LS/Placebo	Healthy children aged 5-17 months receive a single dose of 10-20 mg/kg L9LS via subcutaneous administration. Six months later, participants receive a single dose of placebo via subcutaneous administration. L9LS: Administered subcutaneously. Placebo: Normal saline administered subcutaneously.
FG017	Efficacy Study: Arm 1b: Age 5-17 Months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS	Healthy children aged 5-17 months receive a single dose of 10-20 mg/kg L9LS via subcutaneous administration. Six months later, participants receive a second single dose of 10-20 mg/kg L9LS via subcutaneous administration. L9LS: Administered subcutaneously.
FG018	Efficacy Study: Arm 1c: Age 5-17 Months, Placebo/Placebo	Healthy children aged 5-17 months receive a single dose of placebo via subcutaneous administration. Six months later, participants receive a second single dose of placebo via subcutaneous administration. Placebo: Normal saline administered subcutaneously.
FG019	Efficacy Study: Arm 2a: Age 18-59 Months, 10-20 mg/kg of L9LS/Placebo	Healthy children aged 18-59 months receive a single dose of 10-20 mg/kg L9LS via subcutaneous administration. Six months later, participants receive a single dose of placebo via subcutaneous administration. L9LS: Administered subcutaneously. Placebo: Normal saline administered subcutaneously.
FG020	Efficacy Study: Arm 2b: Age 18-59 Months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS	Healthy children aged 18-59 months receive a single dose of 10-20 mg/kg L9LS via subcutaneous administration. Six months later, participants receive a second single dose of 10-20 mg/kg L9LS via subcutaneous administration. L9LS: Administered subcutaneously.
FG021	Efficacy Study: Arm 2c: Age 18-59 Months, Placebo/Placebo	Healthy children aged 18-59 months receive a single dose of placebo via subcutaneous administration. Six months later, participants receive a second single dose of placebo via subcutaneous administration. Placebo: Normal saline administered subcutaneously.

Periods

Title

Milestones

Reasons Not Completed

Part 1A: Period 1

Type	Comment	Milestone Data
STARTED		FG0009 subjects FG0013 subjects FG0020 subjects FG0030 subjects FG0040 subjects FG0050 subjects FG0060 subjects FG0070 subjects FG0080 subjects FG0090 subjects FG0100 subjects FG0110 subjects FG0120 subjects FG0130 subjects FG0140 subjects FG0150 subjects FG0160 subjects FG0170 subjects FG0180 subjects FG0190 subjects FG0200 subjects FG0210 subjects
Has Day 7 Data		FG0009 subjects FG0013 subjects FG0020 subjects FG0030 subjects FG004
Completed Three Month Study Follow up		FG0009 subjects FG0013 subjects FG0020 subjects FG0030 subjects FG004
COMPLETED		FG0009 subjects FG0013 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Part 1A: Period 2

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0029 subjects FG003

Part 1A: Period 3

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Part 1A: Period 4

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Part 1B/Part 2 - Period 1

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Part 1B - Period 2

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

ID	Title	Description
BG000	Age De-escalation and Dose-escalation Study: Arm 1a: Age 5-10 Years, 5 mg/kg of L9LS	Healthy children aged 5-10 years receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2. L9LS: Administered subcutaneously.
BG001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Customized			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Local Adverse Events (AEs)

Number of participants with at least one solicited local adverse events occurring within seven days of administration of intervention. Local reactogenicity included injection site pain, tenderness, bruising, swelling, redness, induration, pruritus, and other (e.g. injection site reaction). Adverse events were captured by Investigator examination and history from participants.

Modified intent to treat population

Posted

Count of Participants

Participants

Age De-escalation and Dose escalation: within 7 days of administration of intervention; Efficacy study: within 7 days after first intervention, and 7 days after second intervention (second intervention occurred 6 months post first intervention)

ID	Title	Description
OG000	Age De-escalation and Dose-escalation Study: Arm 1a: Age 5-10 Years, 5 mg/kg of L9LS	Healthy children aged 5-10 years receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2. L9LS: Administered subcutaneously.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Age De-escalation and Dose-escalation Study: Arm 1a: Age 5-10 Years, 5 mg/kg of L9LS	Healthy children aged 5-10 years receive a single dose of 5 mg/kg L9LS via subcutaneous administration. Once subjects reach day 7 post-administration without safety concerns dosing begins for arm 2. L9LS: Administered subcutaneously.

ID	Term
D011528	Protozoan Infections
D010272	Parasitic Diseases
D007239	Infections
D000096724	Mosquito-Borne Diseases