Plasmodium Falciparum InfectionPhase 2NCT05400655
Anti-malaria MAb in Kenyan Children
A Phase 2 study testing L9LS in people with Plasmodium Falciparum Infection and Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Kenya.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 5 months to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum Infection, Malaria
- What is being tested?
- L9LS
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 912 participants
- Where
- 1 siteKenya
- Study dates
- 14 Sep 2022to 2 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 months to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Kenya1 site
Kenya Medical Research Institute (KEMRI) Center for Global Health Research (CGHR)
Kisumu
About this study
Official 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
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.
Read the 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.
- Conditions
- Plasmodium Falciparum Infection, Malaria
- Being tested
- L9LS, Placebo
- Keywords
- monoclonal, antibody, Kenya, malaria, children
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L9LSDrug
Administered subcutaneously.
PlaceboOther
Normal saline administered subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo |
| Age de-escalation and dose-escalation study: Arm 2c: Age 5-10 years, 10 mg/kg of L9LS | Experimental | 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. Receives: Drug: L9LS |
| Age de-escalation and dose-escalation study: Arm 2d: Age 5-10 years, Placebo | Placebo comparator | 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. Receives: Other: Placebo |
| Age de-escalation and dose-escalation study: Arm 3a: Age 5-10 years, 20 mg/kg of L9LS | Experimental | 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. Receives: Drug: L9LS |
| Age de-escalation and dose-escalation study: Arm 3b: 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 4. Receives: Other: Placebo |
| Age de-escalation and dose-escalation study: Arm 3c: Age 5-59 months, 10 mg/kg of L9LS | Experimental | 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. Receives: Drug: L9LS |
| Age de-escalation and dose-escalation study: Arm 3d: 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 4. Receives: Other: Placebo |
| Age de-escalation and dose-escalation study: Arm 4a: Age 5-59 months, 20 mg/kg of L9LS | Experimental | Healthy children aged 5-59 months receive a single dose of 20 mg/kg of L9LS one-time via subcutaneous administration. Receives: Drug: L9LS |
| Age de-escalation and dose-escalation study: Arm 4b: Age 5-59 months, Placebo | Placebo comparator | Healthy children aged 5-59 months receive a single dose of placebo via subcutaneous administration. Receives: Other: Placebo |
| Age de-escalation and dose-escalation study: Arm 5a: Age 5-71 months, 30 mg/kg of L9LS | Experimental | 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. Receives: Drug: L9LS |
| Age de-escalation and dose-escalation study: Arm 5b: Age 5-71 months, Placebo | Placebo comparator | 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. Receives: Other: Placebo |
| Age de-escalation and dose-escalation study: Arm 6a: Age 5-71 months, 40 mg/kg of L9LS | Experimental | Healthy children aged 5-71 months receive a single dose of 40 mg/kg L9LS via subcutaneous administration. Receives: Drug: L9LS |
| Age de-escalation and dose-escalation study: Arm 6b: Age 5-71 months, Placebo | Placebo comparator | Healthy children aged 5-71 months receive a single dose of placebo via subcutaneous administration. Receives: Other: Placebo |
| Efficacy Study: Arm 1a: Age 5-17 months, 10-20 mg/kg of L9LS/Placebo | Experimental | 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. Receives: Drug: L9LS; Other: Placebo |
| Efficacy Study: Arm 1b: Age 5-17 months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS | Experimental | 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. Receives: Drug: L9LS |
| Efficacy Study: Arm 1c: Age 5-17 months, Placebo/Placebo | Placebo comparator | 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. Receives: Other: Placebo |
| Efficacy Study: Arm 2a: Age 18-59 months, 10-20 mg/kg of L9LS/Placebo | Experimental | 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. Receives: Drug: L9LS; Other: Placebo |
| Efficacy Study: Arm 2b: Age 18-59 months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS | Experimental | 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. Receives: Drug: L9LS |
| Efficacy Study: Arm 2c: Age 18-59 months, Placebo/Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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) (by Grade)
The severity of systemic adverse events occurring after the administration of L9LS was assessed using the grading scale below:
Grade 1: Fever = 37.5^oC-37.9^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38^oC-38.4^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever > 24 hours or some interference with activity; Nausea = Some interference with activity or > 2 episodes/24 hours Grade 3: Fever = 38.5^oC-39.5^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = > 39.5^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock
Grade 5: Death
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2022
- Study start14 Sep 2022
- Primary completion2 Jun 2024
- Study completion2 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Falciparum InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 912 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Centers for Disease Control and Prevention, National Institutes of Health (NIH), Kenya Medical Research Institute, Liverpool School of Tropical Medicine
- Responsible party
- Sponsor
- Investigators
- Titus Kwambai, MD, PhD, Principal investigator, Centers for Disease Control and PreventionLaura Steinhardt, PhD, MPH, Principal investigator, Centers for Disease Control and PreventionPeter D Crompton, MD, MPH, Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05400655
- Sponsor's protocol ID
- SERU 4413
- Status last verified
- Sep 2025
- First submitted
- 12 May 2022
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data from this study may be requested from other researchers indefinitely after the completion of the primary endpoint by contacting one of the principal investigators.
Publications
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.
PubMed 42035777
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT05400655
- Acronym / sponsor ID
- SERU 4413
- Conditions
- Plasmodium Falciparum Infection, Malaria
- Keywords
- monoclonal, antibody, Kenya, malaria, children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 912 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Centers for Disease Control and Prevention, National Institutes of Health (NIH), Kenya Medical Research Institute, Liverpool School of Tropical Medicine
- Study start
- 14 Sep 2022 (actual)
- Primary completion
- 2 Jun 2024 (actual)
- Study completion
- 2 Jun 2024 (actual)
- First posted
- 1 Jun 2022 (actual)
- Results
- Posted 16 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 22
| Arm | Type | Receives |
|---|---|---|
| Age de-escalation and dose-escalation study: Arm 1a: Age 5-10 years, 5 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 1b: Age 5-10 years, Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 2a: Age 5-59 months, 5 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 2b: Age 5-59 months, Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 2c: Age 5-10 years, 10 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 2d: Age 5-10 years, Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 3a: Age 5-10 years, 20 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 3b: Age 5-10 years, Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 3c: Age 5-59 months, 10 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 3d: Age 5-59 months, Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 4a: Age 5-59 months, 20 mg/kg of L9LS | Experimental | Drug: L9LSHealthy children aged 5-59 months receive a single dose of 20 mg/kg of L9LS one-time via subcutaneous administration. |
| Age de-escalation and dose-escalation study: Arm 4b: Age 5-59 months, Placebo | Placebo comparator | Other: PlaceboHealthy children aged 5-59 months receive a single dose of placebo via subcutaneous administration. |
| Age de-escalation and dose-escalation study: Arm 5a: Age 5-71 months, 30 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 5b: Age 5-71 months, Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Age de-escalation and dose-escalation study: Arm 6a: Age 5-71 months, 40 mg/kg of L9LS | Experimental | Drug: L9LSHealthy children aged 5-71 months receive a single dose of 40 mg/kg L9LS via subcutaneous administration. |
| Age de-escalation and dose-escalation study: Arm 6b: Age 5-71 months, Placebo | Placebo comparator | Other: PlaceboHealthy children aged 5-71 months receive a single dose of placebo via subcutaneous administration. |
| Efficacy Study: Arm 1a: Age 5-17 months, 10-20 mg/kg of L9LS/Placebo | Experimental | Drug: L9LS, Other: PlaceboHealthy 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. |
| Efficacy Study: Arm 1b: Age 5-17 months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Efficacy Study: Arm 1c: Age 5-17 months, Placebo/Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
| Efficacy Study: Arm 2a: Age 18-59 months, 10-20 mg/kg of L9LS/Placebo | Experimental | Drug: L9LS, Other: PlaceboHealthy 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. |
| Efficacy Study: Arm 2b: Age 18-59 months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS | Experimental | Drug: L9LSHealthy 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. |
| Efficacy Study: Arm 2c: Age 18-59 months, Placebo/Placebo | Placebo comparator | Other: PlaceboHealthy 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. |
Who may qualify
- Ages
- 5 months to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L9LSAdministered subcutaneously. | Drug | 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, Age de-escalation and dose-escalation study: Arm 2c: Age 5-10 years, 10 mg/kg of L9LS, Age de-escalation and dose-escalation study: Arm 3a: Age 5-10 years, 20 mg/kg of L9LS, Age de-escalation and dose-escalation study: Arm 3c: Age 5-59 months, 10 mg/kg of L9LS, Age de-escalation and dose-escalation study: Arm 4a: Age 5-59 months, 20 mg/kg of L9LS, Age de-escalation and dose-escalation study: Arm 5a: Age 5-71 months, 30 mg/kg of L9LS, Age de-escalation and dose-escalation study: Arm 6a: Age 5-71 months, 40 mg/kg of L9LS, Efficacy Study: Arm 1a: Age 5-17 months, 10-20 mg/kg of L9LS/Placebo, Efficacy Study: Arm 1b: Age 5-17 months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS, Efficacy Study: Arm 2a: Age 18-59 months, 10-20 mg/kg of L9LS/Placebo, Efficacy Study: Arm 2b: Age 18-59 months, 10-20 mg/kg of L9LS/10-20 mg/kg of L9LS |
| PlaceboNormal saline administered subcutaneously. | Other | Age de-escalation and dose-escalation study: Arm 1b: Age 5-10 years, Placebo, Age de-escalation and dose-escalation study: Arm 2b: Age 5-59 months, Placebo, Age de-escalation and dose-escalation study: Arm 2d: Age 5-10 years, Placebo, Age de-escalation and dose-escalation study: Arm 3b: Age 5-10 years, Placebo, Age de-escalation and dose-escalation study: Arm 3d: Age 5-59 months, Placebo, Age de-escalation and dose-escalation study: Arm 4b: Age 5-59 months, Placebo, Age de-escalation and dose-escalation study: Arm 5b: Age 5-71 months, Placebo, Age de-escalation and dose-escalation study: Arm 6b: Age 5-71 months, Placebo, Efficacy Study: Arm 1a: Age 5-17 months, 10-20 mg/kg of L9LS/Placebo, Efficacy Study: Arm 1c: Age 5-17 months, Placebo/Placebo, Efficacy Study: Arm 2a: Age 18-59 months, 10-20 mg/kg of L9LS/Placebo, Efficacy Study: Arm 2c: Age 18-59 months, Placebo/Placebo |
Primary outcome
Number of Participants With Local Adverse Events (AEs)
Time frame: 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 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.
Number of Participants With Local Adverse Events (AEs) (by Grade)
Time frame: 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)
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
Number of Participants With Systemic Adverse Events (AEs)
Time frame: 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 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.
Number of Participants With Systemic Adverse Events (AEs) (by Grade)
Time frame: 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)
The severity of systemic adverse events occurring after the administration of L9LS was assessed using the grading scale below: Grade 1: Fever = 37.5^oC-37.9^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38^oC-38.4^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever > 24 hours or some interference with activity; Nausea = Some interference with activity or > 2 episodes/24 hours Grade 3: Fever = 38.5^oC-39.5^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = > 39.5^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock Grade 5: Death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42035777Steinhardt 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.
- Individual participant dataSharing planned: Yes. Data from this study may be requested from other researchers indefinitely after the completion of the primary endpoint by contacting one of the principal investigators.
Related trials for Plasmodium Falciparum Infection
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Titus Kwambai, MD, PhD principal investigator
Centers for Disease Control and Prevention
Laura Steinhardt, PhD, MPH principal investigator
Centers for Disease Control and Prevention
Peter D Crompton, MD, MPH principal investigator
National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L9LS in people with Plasmodium Falciparum Infection and Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Local Adverse Events (AEs) (time frame: 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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05400655, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.