Trial to Evaluate L9LS in Healthy Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

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
    

Intervention name(s): VRC-MALMAB0114-00-AB; Plasmodium falciparum (P. falciparum) sporozoite challenge
Intervention type(s): Drug; Other
Intervention description(s): VRC-MALMAB0114-00-AB (L9LS) is a monoclonal antibody that binds an epitope of the Plasmodium falciparum circumsporozoite protein.; Participants were exposed to bites on the forearm from mosquitoes infected with Plasmodium falciparum
Other intervention name(s): L9LS
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria Parasitemia; Malaria Challenge; First in Human; Mosquito; Prevention