L9LS antibody to prevent malaria in women of childbearing age in Mali

Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Randomized, Double-Blind, Placebo-Controlled Trial of Women of Childbearing Potential (WOCBP) in Mali

This will test whether a one-time subcutaneous injection of the L9LS antibody can protect women of childbearing age in Mali from malaria over a six-month season.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 290 (estimated)
• Ages: 18 Years to 49 Years
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Drugs / interventions: prednisone
• Locations: 3 sites (Faladié, Koulikoro and 2 other locations)
• Trial ID: NCT07060508 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 2 study gives a single 1800 mg subcutaneous dose of L9LS or placebo to women of childbearing potential, with a separate open-label male pharmacokinetic arm. All participants receive artemether-lumefantrine before dosing to clear any existing blood-stage Plasmodium falciparum infection. The main goal is to measure safety and whether L9LS prevents naturally occurring Pf infection across a 24-week follow-up that includes frequent clinic visits and blood testing. About 270 women are weight-stratified into two treatment arms (L9LS or placebo) and followed every 2 weeks through the malaria season to detect infections and monitor labs and clinical signs.

Who should consider this trial

Good fit: Ideal candidates are women aged 18–49 who weigh 45–90 kg, live near the participating clinics in Kalifabougou, Faladje, or Torodo in Koulikoro, Mali, are of childbearing potential and willing to use reliable contraception, while healthy men 18–49 may join the separate open-label PK arm.

Not a fit: People who are pregnant, outside the age or weight limits, have significant medical conditions, cannot commit to contraception requirements, or cannot remain in the study area for follow-up are not eligible and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, L9LS could offer safe, long-acting protection against Plasmodium falciparum infection for women during a malaria season, reducing illness and the need for repeated treatments.

How similar studies have performed: Early-phase trials of other monoclonal antibodies targeting P. falciparum have shown protective signals, but larger field efficacy data from Phase 2 studies remain limited.

Eligibility criteria

Inclusion Criteria:

1. Females aged ≥18 and ≤49 years and weighing ≥ 45.0 and ≤ 90.0 kg.
2. Males aged ≥18 and ≤49 years (no weight restrictions).
3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
4. In good general health and without clinically significant medical history.
5. Able to provide informed consent.
6. Willing to have blood samples and data stored for future research.
7. Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study.
8. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to study Day 0 through the final study visit as described below.

   1. Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device.

Exclusion Criteria:

1. Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β hCG) test (if female).
2. Currently breastfeeding.
3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol.
4. Study comprehension examination score of \<80% correct or per investigator discretion.
5. Hemoglobin, WBC, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
6. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
7. Infected with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).
8. Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.)
9. Clinically significant abnormal electrocardiogram (ECG; QTc \>460 or other significant abnormal findings, including unexplained tachycardia or bradycardia).
10. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
11. Receipt of any investigational product within the past 30 days.
12. Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. \[Note: Past, current, or planned participation in observational studies is NOT exclusionary; participation in the placebo arm of the Mali adult CIS43LS MAb trial (ClinicalTrials.gov Identifier: NCT04329104) or the placebo arm of the Mali adult L9LS Mab trial (ClinicalTrials.gov Identifier: NCT05816330) is NOT exclusionary.\]
13. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
14. History of a severe allergic reaction or anaphylaxis.
15. Severe asthma (defined as asthma that is unstable or required emergent 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).
16. Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia.
17. Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors).
18. Known immunodeficiency syndrome.
19. Known asplenia or functional asplenia.
20. 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.
21. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration.
22. Receipt of immunoglobulins and/or blood products within the past 6 months.
23. Previous receipt of an investigational malaria vaccine or MAb in the last 5 years.
24. Known allergies or contraindication against artemether lumefantrine.
25. Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or render the participant unable to comply with the protocol.

Where this trial is running

Faladié, Koulikoro and 2 other locations

• Faladje MRTC Clinic — Faladié, Koulikoro, Mali (Recruiting)
• Kalifabougou MRTC Clinic — Kalifabougou, Koulikoro, Mali (Recruiting)
• Torodo MRTC Clinic — Torodo, Koulikoro, Mali (Recruiting)

Study contacts

• Principal investigator: Peter Crompton, MD, MPH — National Institutes of Health (NIH)
• Study coordinator: Kassoum Kayentao, MD, MPH, PhD

Conditions Malaria