L9LS MAb in Malian Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of a one time SC administration of L9LS in healthy adults in Mali, as well as its protective efficacy against naturally occurring Plasmodium falciparum (Pf) infection over a 6-month malaria season. A secondary objective is to determine if SC administration of L9LS at 900 mg (compared to placebo) mediates protection against naturally occurring Pf infection in healthy Malian adult females stratified by weight during a single malaria season.

Detailed Description
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A phase 2 trial evaluating the safety and tolerability of a one time subcutaneous (SC) administration of L9LS, as well its protective efficacy against naturally occurring Pf infection over a 6-month malaria season. The primary study hypotheses is that L9LS will be safe and protective against malaria infection. As a secondary objective, the efficacy of L9LS within three body weight strata among female participants will each be compared to placebo. Before study agent administration, all subjects will be given artemether lumefantrine to clear any preexisting Pf blood stage infection. The study is a randomized, double-blind, placebo-controlled, sex-stratified (2:1 female to male ratio) and weight-stratified trial (N=288 total) with 2 treatment arms: L9LS 900 mg SC (n=216) and placebo (n=72) to assess safety and protective efficacy of L9LS compared to placebo. Subjects will receive the study agent and be followed at study visits 1, 3, 7, 14, 21, and 28 days later, and once every 2 weeks thereafter through 24 weeks. Primary study assessments include physical examination and blood collection for identification of Pf infection and other research laboratory evaluations.

Official Title
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Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Randomized, Double-Blind, Placebo-Controlled Trial of Adults in Mali

Conditions
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Plasmodium Falciparum Infection, Malaria

Intervention / Treatment
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* Biological: L9LS (VRC-MALMAB0114-00-AB)
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged ≥18 and ≤49 years and weighing ≥ 45.0 and ≤ 90.0 kg. Males aged ≥18 and ≤55 years and weighing ≥ 50.0 and ≤ 100.0 kg. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. In good general health and without clinically significant medical history. Able to provide informed consent. Willing to have blood samples and data stored for future research. Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study. 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. Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device. Nonchildbearing women will be required to report date of last menstrual period, history of surgical sterility (i.e., tubal ligation, hysterectomy) or premature ovarian insufficiency, and will have urine or serum pregnancy tests performed per protocol. Exclusion Criteria: Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β hCG) test (if female). Currently breastfeeding. 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. Study comprehension examination score of <80% correct or per investigator discretion. Hemoglobin, 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 not clinically significant values.) 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 not clinically significant values.) Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.) Clinically significant abnormal electrocardiogram (ECG; QTc >460 or other significant abnormal findings, including unexplained tachycardia or bradycardia). 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. Receipt of any investigational product within the past 30 days. 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) is NOT exclusionary.] Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. History of a severe allergic reaction or anaphylaxis. 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). 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. Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors). Known immunodeficiency syndrome. Known asplenia or functional asplenia. 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. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration. Receipt of immunoglobulins and/or blood products within the past 6 months. Previous receipt of an investigational malaria vaccine or monoclonal antibody in the last 5 years. Known allergies or contraindication against artemether lumefantrine. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: 900 mg of L9LS SC<br>Participants will receive 900 mg of L9LS SC. | Biological: L9LS (VRC-MALMAB0114-00-AB)<br>* Administered one time via subcutaneous route.<br>|
| Placebo Comparator: Arm 2: Placebo (normal saline) SC<br>Participants will receive placebo of Normal Saline for comparison. | Other: Normal Saline<br>* Administered one time via subcutaneous route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of local and systemic AEs occurring within 7 days after the administration of study agent. |  | Measured through Day 7 | 
| Severity of local and systemic AEs occurring within 7 days after the administration of study agent. |  | Measured through Day 7 | 
| Occurrence of Pf blood-stage infection | Detected by microscopic examination of thick blood smear for 24 weeks after administration of study agent. | Measured through Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pf blood-stage infection as detected by RT-PCR for 24 weeks after administration of study agent. |  | Measured through week 24 | 
| Measurement of L9LS in sera of recipients. |  | Measure through week 24 |