NCT05019729

Trial to Evaluate L9LS in Healthy Adults

VRC 614: A Phase 1, Dose Escalation, Open-Label Clinical Trial With Experimental Controlled Human Malaria Infections (CHMI) to Evaluate Safety and Protective Efficacy of an Anti-Malaria Human Monoclonal Antibody, VRC-MALMAB0114-00-AB (L9LS), in Healthy Malaria-Naive Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Background: Malaria is a parasitic disease carried by mosquitoes in tropical areas. There is no vaccine to prevent malaria infection. If not treated right away, it can become serious or deadly. Researchers want to test a drug to prevent malaria. Objective: To test if the drug L9LS is safe and if it prevents malaria infection in people. Eligibility: Healthy adults ages 18-50 who have never had malaria. Design: Participants were screened with a medical history, physical exam, and blood tests. Participants were divided into 6 groups: * Three groups received L9LS by infusion into a vein, and gave blood samples before and after infusion. * One group received L9LS injected into the fat under the skin. * One group did not get L9LS. * One group received L9LS injected into the muscle. All participants who received L9LS were monitored for side effects. They had 2-3 follow-up visits during the week after the drug was given, and gave blood samples. They received a thermometer to check their temperature daily for 7 days. They received a tool to measure any redness, swelling, or bruising at the injection site. Most participants took part in the controlled human malaria infection (CHMI) or malaria challenge to find out if L9LS prevents malaria after being bitten by infected mosquitos. Participants in the group who received L9LS injected in the muscle were enrolled after CHMI and did not take part in the CHMI. Participants who received CHMI were bitten by mosquitoes carrying the malaria parasites. A cup containing mosquitoes was placed on their arm for 5 minutes. On days 7-17 after exposure, they received daily study visits to give blood samples. Those who got malaria were treated immediately. On day 21, all CHMI participants received treatment for malaria. Participation lasted 2-6 months, depending on study group.

Detailed description

This was a Phase 1, open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and protective efficacy of an anti-malaria human monoclonal antibody, VRC-MALMAB0114-00-AB (L9LS). The primary hypothesis was that L9LS will be safe and well tolerated when administered by either intravenous (IV),subcutaneous (SC) or intramuscular (IM) routes. The secondary objectives were that L9LS will be detectable in human sera with a definable half-life and confer protection following a controlled human malaria infection (CHMI). The study started with enrollment into Group 1. Interim safety evaluations occurred and supported continued evaluation of L9LS prior to enrolling participants into additional dose groups. All L9LS recipients in Groups 1-4 were invited to participate in the CHMI. Group 5 participants did not receive L9LS, in order to serve as the control group for the CHMI. After CHMI, all CHMI participants were evaluated for malaria parasitemia. Participants who developed blood stage infection were treated as soon as identified per protocol criteria. Participants in Group 6 received L9LS but did not take part in the CHMI. Study follow-up continued through 24 weeks post product administration or 8 weeks post- CHMI, whichever was the most stringent. Study Groups: Group 1: 5 participants - 1mg/kg IV + CHMI Group 2: 4 participants - 5 mg/kg IV + CHMI (1 participant declined to participate in the CHMI) Group 3: 5 participants - 5 mg/ kg SC + CHMI Group 4: 4 participants - 20 mg/kg IV + CHMI Group 5: 9 participants - CHMI Controls (No L9LS given; 3 back up participants were not needed so were terminated early and did not participate in the CHMI) Group 6: 5 participants - 5 mg/kg IM

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	VRC-MALMAB0114-00-AB	VRC-MALMAB0114-00-AB (L9LS) is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozoite protein.
OTHER	Plasmodium falciparum (P. falciparum) sporozoite challenge	Participants were exposed to bites on the forearm from mosquitoes infected with Plasmodium falciparum

Timeline

• Start date: 2021-09-13
• Primary completion: 2022-09-19
• Completion: 2022-09-19
• First posted: 2021-08-25
• Last updated: 2024-08-14
• Results posted: 2023-10-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study