L9LS MAb in Malian Adults

NCT05816330 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2023/109/CE/USTTB
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Plasmodium Falciparum Infection; Malaria

Keywords

Malaria; Plasmodium falciparum; L9LS; Monoclonal antibodies

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Local Adverse Events (AEs)

  Number of participants with local adverse events occurring within 7 days after administration of L9LS. Local reactogenicity included pain/tenderness, swelling, redness, bruising, and pruritus at the site of infusion. Adverse events were captured by Investigator examination and history from participants.

  Within 7 days after administration of intervention

• Number of Participants With Systemic Adverse Events (AEs)

  Number of participants with local adverse events occurring within 7 days after administration of L9LS. Systemic reactogenicity events included fever, feeling unusually tired or unwell, muscle aches, headache, chills, nausea, and joint pain. Adverse events were captured by Investigator examination and history from participants.

  Within 7 days after administration of 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

  Within 7 days after administration of 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

  Within 7 days after administration of intervention

• Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination for Thick Blood Smear

  Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood smear-positive for Pf was assessed by microscopic examination of thick blood smear collected from participants from day 7 through week 24 (168 days) after administration of L9LS or placebo. Sample was collected every two weeks from day seven until week 24. Analysis was done as number of participants who had at least one positive blood smear.

  Day 7 through week 24

Secondary Outcomes (4)

• Participants With Plasmodium Falciparum (Pf) Infection Detected by Real-Time Polymerase Chain Reaction (RT-PCR)

  Day 7 through week 24

• Maximum Total Plasma Concentration (Cmax) for L9LS

  Measure through week 24

• Time to Maximum Plasma Concentration (TMax) for L9LS - Hours

  Day 7 post administration of drug

• Time to Maximum Plasma Concentration (TMax) for L9LS - Days

  Measure through week 24

Study Arms (2)

L9LS 900 mg

EXPERIMENTAL

Adult participants receive a single dose of L9LS 900 mg subcutaneously.

Biological: L9LS (VRC-MALMAB0114-00-AB)

Placebo

PLACEBO COMPARATOR

Adult participants receive a single dose of Placebo subcutaneously.

Other: Placebo

Interventions

L9LS (VRC-MALMAB0114-00-AB) BIOLOGICAL

Administered one time via subcutaneous route.

L9LS 900 mg

Placebo OTHER

Normal saline administered one time via subcutaneous route.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.
• 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).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• Malaria Research and Training Center, Bamako, Mali: collaborator
• University of the Sciences, Techniques and Technologies of Bamako: collaborator
• University of Washington: collaborator
• Harvard School of Public Health (HSPH): collaborator
• Indiana University School of Medicine: collaborator

Study Sites (3)

Faladje MRTC Clinic

Faladiè, Koulikoro, Mali

Location

Kalifabougou MRTC Clinic

Kalifabougou, Koulikoro, Mali

Location

Torodo MRTC Clinic

Torodo, Koulikoro, Mali

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Peter D Crompton
• Organization: National Institute of Allergy and Infectious Diseases (NIAID)

pcrompton@niaid.nih.gov

301-761-5042

Study Officials

• Kassoum Kayentao, MD, MPH, PhD

  Faculté de Médecine Pharmacie d'Odontostomatologie (FMPOS)

  PRINCIPAL INVESTIGATOR

• Peter Crompton, MD, MPH

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2023
• First Posted: April 18, 2023
• Study Start: May 25, 2023
• Primary Completion: February 11, 2024
• Study Completion: February 11, 2024
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be shared at the time of publication or shortly thereafter.
• Access Criteria: Data from this study may be requested from other researchers indefinitely after the completion of the primary endpoint by contacting Laboratory of Immunogenetics at NIH

Locations

MA (3)