L9LS MAb in Malian Infants

NCT06461026 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2024/158/CE/USTTB
• Study Type: interventional
• Target: 327
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of L9LS in infants in Mali and to evaluate the impact of L9LS on subsequent R21/Matrix-MTM vaccine immunogenicity.

Conditions

Malaria

Outcome Measures

Primary Outcomes (4)

• Participants With Local Adverse Events (AEs)

  Number of participants with local adverse events occurring within 7 days after administration of L9LS or placebo intervention. 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 L9LS or matching Placebo intervention (administered on Day 0)

• Severity of Local Adverse Events (AEs)

  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 L9LS or matching Placebo intervention (administered on Day 0)

• Participants With Systemic Adverse Events (AEs)

  Number of participants with local adverse events occurring within 7 days after administration of L9LS or placebo intervention. 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 L9LS or matching Placebo intervention (administered on Day 0)

• Severity of Systemic Adverse Events (AEs)

  The severity of systemic AEs after the administration of L9LS or placebo 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 L9LS or matching Placebo intervention (administered on Day 0)

Secondary Outcomes (10)

• Participants With Adverse Events of Special Interest (AESIs) Related to R21/Matrix-MTM Vaccine

  Within 7 days after administration of each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196)

• Severity of Adverse Events of Special Interest (AESIs)

  Within 7 days after administration of each dose of the R21/Matrix-MTM vaccine (administered on days 140, 168, 196)

• Antibody Response to R21/Matrix-MTM Vaccine

  Measured 28 days (Day 224) and 84 days (Day 280) after the third dose of R21/Matrix-MTM vaccination

• Maximum Total Plasma Concentration (Cmax) for L9LS

  Days 0 to 280

• Time to Maximum Plasma Concentration (TMax) for L9LS

  Days 0 to 280

Other Outcomes (1)

• Participants With Plasmodium Falciparum (Pf) Detected by Microscopic Examination

  Measured days 7, 28, 84, 140, 196, 224, and 280

Study Arms (6)

Infants 1-4 months: L9LS 150 mg

EXPERIMENTAL

Infants age 1-4 months received a single dose of L9LS 150 mg intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Biological: L9LS; Biological: R21/Matrix-MTM

Infants 5-8 months: L9LS 150 mg

EXPERIMENTAL

Infants age 5-8 months received a single dose of L9LS 150 mg intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Biological: L9LS; Biological: R21/Matrix-MTM

Infants 9-12 months: L9LS 150 mg

EXPERIMENTAL

Infants age 9-12 months received a single dose of L9LS 150 mg intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Biological: L9LS; Biological: R21/Matrix-MTM

Infants 1-4 months: Placebo

PLACEBO COMPARATOR

Infants age 1-4 months received a single dose of normal saline placebo intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Other: Placebo; Biological: R21/Matrix-MTM

Infants 5-8 months: Placebo

PLACEBO COMPARATOR

Infants age 5-8 months received a single dose of normal saline placebo intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Other: Placebo; Biological: R21/Matrix-MTM

Infants 9-12 months: Placebo

PLACEBO COMPARATOR

Infants age 9-12 months received a single dose of normal saline placebo intramuscularly. Approximately five months after receiving intervention, participants received the R21/Matrix-MTM vaccine 0.5ml (dose has 5mcg of malaria /50mcg of the adjuvant) intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Other: Placebo; Biological: R21/Matrix-MTM

Interventions

Placebo OTHER

Normal Saline administered intramuscularly one time.

Infants 1-4 months: Placebo; Infants 5-8 months: Placebo; Infants 9-12 months: Placebo

R21/Matrix-MTM BIOLOGICAL

Administered intramuscularly as three total doses given four weeks apart on days 140, 168, 196.

Infants 1-4 months: L9LS 150 mg; Infants 1-4 months: Placebo; Infants 5-8 months: L9LS 150 mg; Infants 5-8 months: Placebo; Infants 9-12 months: L9LS 150 mg; Infants 9-12 months: Placebo

L9LS BIOLOGICAL

Administered intramuscularly one time.

Infants 1-4 months: L9LS 150 mg; Infants 5-8 months: L9LS 150 mg; Infants 9-12 months: L9LS 150 mg

Eligibility Criteria

• Age: 1 Month - 12 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥1 to ≤12 months at enrollment.
• Born at ≥37 weeks gestation.
• Parent and/or guardian 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.
• Parent and/or guardian 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.

You may not qualify if:

• Body weight \<3.5 kg.
• Behavioral, cognitive, or psychiatric disease in the parent and/or guardian that in the opinion of the investigator affects the ability of the parent and/or guardian to understand and comply with the study protocol.
• Any fever (≥ 37.5°C, regardless of route) or acute illness within 7 days prior to randomization.
• Clinically significant congenital anomaly or documented or suspected serious medical illness (e.g., history of epilepsy), serious congenital anomaly, or immediate life-threatening condition in the infant that may interfere with the ability to complete study requirements, as judged by the examining clinician.
• Prior history of a suspected or actual acute life-threatening event.
• Receipt of any blood products, monoclonal or polyclonal antibody/immunoglobulin (for example, hepatitis B immune globulin, intravenous immunoglobulin) or anticipated use during the study.
• Any acute or chronic illnesses known in the mother during her pregnancy.
• Parental study comprehension examination score of \<80% correct or per investigator discretion.
• Hemoglobin, white blood cell (WBC), absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
• Alanine aminotransferase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
• Mother and/or infant infected with HIV.
• 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.
• History of a severe allergic reaction or anaphylaxis.
• 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
• University of Washington: collaborator
• Harvard School of Public Health (HSPH): collaborator
• Indiana University: collaborator

Study Sites (3)

Faladje MRTC Clinic

Faladié, Koulikoro, Mali

Location

Kalifabougou MRTC Clinic

Kalifabougou, Koulikoro, Mali

Location

Torodo MRTC Clinic

Torodo, Koulikoro, Mali

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

pcrompton@niaid.nih.gov

301-761-5042

Study Officials

• Peter Crompton, MD, MPH

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

• Kassoum Kayentao, MD, MPH, PhD

  Faculté de Médecine Pharmacie d'Odontostomatologie (FMOS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2024
• First Posted: June 14, 2024
• Study Start: August 19, 2024
• Primary Completion: June 27, 2025
• Study Completion: June 27, 2025
• Last Updated: October 1, 2026
• Results First Posted: September 3, 2026

Record last verified: 2026-09

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.

Locations

MA (3)