Safety, Pharmacokinetics, and Plasmodium Falciparum Transmission-reducing Activity of Monoclonal Antibody TB31F in Mali

NCT06413108 | Completed Phase 1 DMC

• 1 other identifier: TB31F Mali
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 1

Brief Summary

Mali faces a significant challenge with malaria, particularly among its younger population. While existing measures like seasonal chemoprevention and vaccination have shown efficacy, further innovations are necessary to combat this disease. The monoclonal antibody TB31F shows promise in reducing the transmission of malaria. This clinical trial will evaluate the safety and efficacy of the monoclonal antibody TB31F.

Conditions

Malaria,Falciparum

Keywords

transmission-reducing; monoclonal antibody

Outcome Measures

Primary Outcomes (9)

• Occurrence of at least possibly related solicited local and systemic adverse events

  within 7 days of monoclonal antibody TB31F administration

• Occurrence of at least possibly related unsolicited adverse events

  within 28 days of monoclonal antibody TB31F administration

• Occurrence of at least possibly related serious adverse events

  from enrollment to the end of follow-up at 28 or 84 days

• Terminal serum half-life (t½) of monoclonal antibody TB31F in serum

  day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.

• Maximum observed serum concentration (Cmax) of monoclonal antibody TB31F in serum

  day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.

• Time to reach maximum serum concentration (tmax) of monoclonal antibody TB31F in serum

  day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.

• Accumulation index (Racc) of monoclonal antibody TB31F in serum

  day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.

• Area under the serum concentration-time curve (AUC0-τ, AUC0-t and AUC) of monoclonal antibody TB31F in serum

  day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.

• Within-group percent reduction in the proportion of mosquitoes infected at day 5 post-treatment compared to baseline (day 0), assessed through direct membrane feeding assays and measured as oocyst prevalence

  day 0 [baseline] & 5

Secondary Outcomes (9)

• Within-group percent reduction in the proportion of mosquitoes infected in direct skin feeding assay (DSF), compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

  day 0 [baseline], 1, and 5

• Within-group percent reduction in the proportion of mosquitoes infected in direct membrane feeding assays (DMFA), compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

  day 0 [baseline], 1, 5, and 14

• Mosquito infection prevalence, assessed by direct skin feed and measured as the proportion dissected mosquitoes with any number of oocysts, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

  day 0 [baseline], 1, and 5

• Mosquito infection prevalence, assessed by DMFA and measured as the proportion dissected with any number of oocysts, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

  day 0 [baseline], 1, 5, and 14

• Mosquito infection intensity, assessed by direct skin feed and measured as the number of oocysts in dissected mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

  day 0 [baseline], 1, and 5

Other Outcomes (19)

• Total serum immunoglobulin G level

  day 0 [baseline]

• Serum leptin level

  day 0 [baseline]

• Total protein level

  day 0 [baseline]

Study Arms (13)

1A: control

PLACEBO COMPARATOR

0.2 mL normal saline

Other: Normal saline

1B: 10 mg TB31F

EXPERIMENTAL

0.2 mL (10 mg) TB31F

Drug: TB31F

2A: control

PLACEBO COMPARATOR

2 mL normal saline

Other: Normal saline

2B:100 mg TB31F

EXPERIMENTAL

2 mL (100 mg) TB31F

Drug: TB31F

3A: control

PLACEBO COMPARATOR

4 mL normal saline

Other: Normal saline

3B: 200 mg TB31F

EXPERIMENTAL

4 mL (200 mg) TB31F

Drug: TB31F

4A: control

PLACEBO COMPARATOR

0.2 mL normal saline

Other: Normal saline

4B: 10 mg TB31F

EXPERIMENTAL

0.2 mL (10 mg) TB31F

Drug: TB31F

5A: control

PLACEBO COMPARATOR

2.0 mL normal saline

Other: Normal saline

5B: 100 mg TB31F

EXPERIMENTAL

2.0 mL (100 mg) TB31F

Drug: TB31F

6A: control

PLACEBO COMPARATOR

0.6 or 2.0 mL normal saline

Other: Normal saline

6B: 30 mg TB31F

EXPERIMENTAL

0.6 mL (30 mg) TB31F

Drug: TB31F

6C: 100 mg TB31F

EXPERIMENTAL

2.0 mL (100 mg) TB31F

Drug: TB31F

Interventions

TB31F DRUG

transmission-blocking monoclonal antibody TB31F

1B: 10 mg TB31F; 2B:100 mg TB31F; 3B: 200 mg TB31F; 4B: 10 mg TB31F; 5B: 100 mg TB31F; 6B: 30 mg TB31F; 6C: 100 mg TB31F

Normal saline OTHER

normal saline as control (placebo)

1A: control; 2A: control; 3A: control; 4A: control; 5A: control; 6A: control

Eligibility Criteria

• Age: 10 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written/signed informed consent
• Adult cohorts: 18-50 years of age
• School-age children cohorts: 10-15 years of age
• Haemoglobin ≥10 g/dL
• Non-lactating females of childbearing potential agree to the use of continuous adequate contraception for 28 days after having received investigational product
• Subject agrees to refrain from blood donation during the study and for 5 months after having received investigational product
• Subjects are available to attend all study visits
• In opinion of the investigator, the subject can and will comply with the requirements of the protocol

You may not qualify if:

• Women who are pregnant (tested at baseline and at day 28 after administration of investigational product by urine and/or serum pregnancy testing (β-hCG)) or lactating
• Symptomatic malaria
• Current acute or chronic disease, including clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history or physical examination
• Clinically significant abnormal blood chemistries and haematology
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 year
• History of adverse reactions to monoclonal antibodies
• Administration of immunoglobulin and/or blood products within the three months preceding the first dose of the investigational product or planned administration during the study period
• Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
• EFFICACY COHORT (STUDY ARM 6)
• Written/signed informed consent
• years of age
• Haemoglobin ≥10 g/dL
• Non-lactating females of childbearing potential agree to the use of continuous adequate contraception for 28 days after having received investigational product
• Subject agrees to refrain from blood donation during the study and for 5 months after having received investigational product
• Subjects are available to attend all study visits

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Malaria Research and Training Center, Bamako, Mali: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of Bamako

Bamako, Point G, BP1805, Mali

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded. The study pharmacist will be unblinded and responsible for randomisation and treatment preparation. Entomology staff involved in the mosquito feeding assays will be blinded for the parasitology results.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will perform two sequential stages of clinical research, each recruiting a distinct cohort of participants to confirm: 1. TB31F safety and 2. TB31F efficacy. The safety cohort will be composed of the three dose groups in adults (groups 1, 2 and 3) and two dose groups in children (groups 4 and 5). The efficacy cohort will be composed of two dose groups in adults and children (group 6). Participants will be randomised within each treatment group to receive a single sub-cutaneous dose of TB31F or placebo.

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 14, 2024
• Study Start: July 12, 2024
• Primary Completion: January 16, 2026
• Study Completion: January 16, 2026
• Last Updated: January 22, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

MA (1)