L9LS-R21 Interaction

NCT07208760 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2025/183/CE/USTTB
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled trial in 2 parts evaluating the effect of 1-time administration of the monoclonal antibody (MAb) L9LS to healthy Malian participants on the immunogenicity of subsequent administration of the R21/Matrix-M™ vaccine. L9LS will be administered subcutaneously (SC) for adults and infants. The study will assess how the timing of L9LS administration impacts immunogenicity following subsequent intramuscular (IM) R21/Matrix-M™ vaccination. Twenty-four adult participants and 333 infant participants will be enrolled.

Conditions

Malaria

Outcome Measures

Primary Outcomes (2)

• Part 1: Incidence and severity of hypersensitivity reactions

  Occurring within 7 days after the administration of the first dose of the R21/Matrix-M™ vaccine.

• Part 2: Total IgG anti-NANP antibody titers

  Measured by ECLIA, using the Meso Scale Discovery (MSD) LLC-based automation platform

  28 days after the third R21/Matrix-M™ vaccination

Secondary Outcomes (8)

• Part 1a: Incidence and severity of local and systemic AEs

  Occurring within 7 days after the administration of L9LS and within 7 days after administration of each dose of R21/Matrix-M™.

• Part 1b: Incidence and severity of laboratory abnormalities

  Occurring within 7 days after the administration of study agent.

• Part 2a: Incidence and severity of local and systemic AEs

  Occurring within 7 days after the administration of L9LS and within 7 days after administration of each dose of R21/Matrix-M™.

• Part 2b: Incidence and severity of laboratory abnormalities

  Occurring within 7 days after the administration of study agent.

• Part 2c: Incidence and severity of hypersensitivity reactions

  Occurring within 7 days after the administration of each dose of R21/Matrix-M™ vaccine.

Study Arms (8)

L9LS in Healthy Malian Adult with R21/Matrix-M™ starting 7 days after

EXPERIMENTAL

L9LS with R21/Matrix-M™ series starting 7 days after.

Drug: Single dose of 1800 mg L9LS SC (12mL)

Placebo in Healthy Malian Adult with R21/Matrix-M™ starting 7 days after

PLACEBO COMPARATOR

Placebo with R21/Matrix-M™ series starting 7 days after.

Other: Placebo 12 mL SC

L9LS in Healthy Malian Infant with R21/Matrix-M™ starting 7 days after

EXPERIMENTAL

L9LS with R21/Matrix-M™ series starting 7 days after.

Drug: Single dose of 225 mg L9LS SC (1.5mL)

Placebo in Healthy Malian Infant with R21/Matrix-M™ starting 7 days after

PLACEBO COMPARATOR

Placebo with R21/Matrix-M™ series starting 7 days after.

Other: Placebo 1.5 mL SC

L9LS in Healthy Malian Infant with R21/Matrix-M™ starting 56 days after

EXPERIMENTAL

L9LS with R21/Matrix-M™ series starting 56 days after.

Drug: Single dose of 225 mg L9LS SC (1.5mL)

Placebo in Healthy Malian Infant with R21/Matrix-M™ starting 56 days after

PLACEBO COMPARATOR

Placebo with R21/Matrix-M™ series starting 56 days after.

Other: Placebo 1.5 mL SC

L9LS in Healthy Malian Infant with R21/Matrix-M™ starting 112 days after

EXPERIMENTAL

L9LS with R21/Matrix-M™ series starting 112 days after.

Drug: Single dose of 225 mg L9LS SC (1.5mL)

Placebo in Healthy Malian Infant with R21/Matrix-M™ starting 112 days after

PLACEBO COMPARATOR

Placebo with R21/Matrix-M™ series starting 112 days after.

Other: Placebo 1.5 mL SC

Interventions

Placebo 12 mL SC OTHER

Normal saline.

Placebo in Healthy Malian Adult with R21/Matrix-M™ starting 7 days after

Single dose of 225 mg L9LS SC (1.5mL) DRUG

A human monoclonal antibody to protect against Plasmodium falciparum.

L9LS in Healthy Malian Infant with R21/Matrix-M™ starting 112 days after; L9LS in Healthy Malian Infant with R21/Matrix-M™ starting 56 days after; L9LS in Healthy Malian Infant with R21/Matrix-M™ starting 7 days after

Placebo 1.5 mL SC OTHER

Normal saline.

Placebo in Healthy Malian Infant with R21/Matrix-M™ starting 112 days after; Placebo in Healthy Malian Infant with R21/Matrix-M™ starting 56 days after; Placebo in Healthy Malian Infant with R21/Matrix-M™ starting 7 days after

Single dose of 1800 mg L9LS SC (12mL) DRUG

A human monoclonal antibody to protect against Plasmodium falciparum.

L9LS in Healthy Malian Adult with R21/Matrix-M™ starting 7 days after

Eligibility Criteria

• Age: 5 Months - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Part 1: Healthy Adults
• Individuals must meet all of the following criteria to be eligible for study participation:
• Male aged ≥18 and ≤50 years weighing ≥50.0 and ≤100.0 kg or female aged ≥18 and ≤50 years weighing ≥45.0 and ≤90.0 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 Sotuba, 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 serum pregnancy test performed per protocol.
• Part 2: Healthy Infants
• Individuals must meet all of the following criteria to be eligible for study participation:
• Aged ≥5 and ≤12 months at enrollment.
• Born at ≥37 weeks gestation (at term).

You may not qualify if:

• Part 1: Healthy Adults
• Individuals meeting any of the following criteria will be excluded from study participation:
• Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin test (if female).
• Currently breastfeeding.
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the prospective participant to understand and comply with the study protocol.
• Study comprehension examination score of \<80% correct or per investigator discretion.
• Hemoglobin, WBC, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. Individuals may be included at the investigator's discretion for "not clinically significant" values.
• ALT or creatinine (Cr) level above the local laboratory-defined upper limit of normal. Individuals may be included at the investigator's discretion for "not clinically significant" values.
• Infection with HIV virus.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies.
• 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, including history of generalized urticaria and angioedema from prior allergic reactions.
• Hypersensitivity to the active substances or to any of the excipients included in the vaccines.
• Hypersensitivity to hepatitis B vaccines.

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Malaria Research and Training Center (MRTC): collaborator
• Faculté de Médecine Pharmacie d'Odontostomatologie (FMOS): collaborator
• University of Sciences, Techniques, and Technologies of Bamako (USTTB): collaborator
• University of Washington: collaborator
• Indiana University School of Medicine, Indiana University: collaborator

Study Sites (1)

Sotuba Malaria Research and Training Center (MRTC)

Sotouba, Mali

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Study Officials

• Bickey H Chang, MD, MHA

  LIG/NIAID/NIH

  PRINCIPAL INVESTIGATOR

• Kassoum Kayentao, MD, MPH, PhD

  MRTC/FMOS/USTTB

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON 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: September 17, 2025
• First Posted: October 6, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

MA (1)