Anti-malaria MAb in Kenyan Children

NCT05400655 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SERU 4413
• Study Type: interventional
• Target: 912
• Locations: 1 country
• Sites: 1

Brief 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) infection among Kenyan children aged 5 to 59 months at enrollment, in a setting of perennial high transmission.

Conditions

Plasmodium Falciparum Infection; Malaria

Keywords

monoclonal; antibody; Kenya; malaria; children

Outcome Measures

Primary Outcomes (4)

• 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.

  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

  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)

Study Arms (22)

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Other: Placebo

Interventions

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; 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

Placebo OTHER

Normal saline administered subcutaneously.

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

Eligibility Criteria

• Age: 5 Months - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Centers for Disease Control and Prevention: collaborator
• National Institutes of Health (NIH): collaborator
• Kenya Medical Research Institute: collaborator
• Liverpool School of Tropical Medicine: collaborator

Study Sites (1)

Kenya Medical Research Institute (KEMRI) Center for Global Health Research (CGHR)

Kisumu, Kenya

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Dr. Laura Steinhardt, PhD, MPH
• Organization: Centers for Disease Control and Prevention

LSteinhardt@cdc.gov

1 6467641472

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: June 1, 2022
• Study Start: September 14, 2022
• Primary Completion: June 2, 2024
• Study Completion: June 2, 2024
• Last Updated: October 16, 2025
• Results First Posted: October 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data may be requested at the time of publication or thereafter
• Access Criteria: * De-identified data with approved outside collaborators under appropriate agreements. * De-identified results or data in publication and/or public presentations.

Locations

KE (1)