Skip to main content
OpenTrials
Completed

NCT Number: NCT06413108

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Malaria,Falciparum Infections Malaria Malaria, Falciparum Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

10 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

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

Bamako, Point G, BP1805, Mali

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

SAFETY COHORT (STUDY ARM 1-5)

Inclusion criteria

  • 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

Exclusion criteria

  • 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)

Inclusion criteria

  • Written/signed informed consent
  • 10-50 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
  • Asymptomatic P. falciparum mono-infection with asexual parasite densities <3000 parasites/µL
  • Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/µL

Exclusion criteria

  • 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 years
  • 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
  • Use of anti-malarial drug treatment in the last 14 days
  • Prior receipt of an antimalarial monoclonal antibody
  • Prior receipt of a P. falciparum transmission-blocking vaccine

Treatment and study plan

TB31F

Drug

transmission-blocking monoclonal antibody TB31F

Normal Saline

Other

normal saline as control (placebo)

Primary outcomes

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

    Time frame: within 7 days of monoclonal antibody TB31F administration

  2. Occurrence of at least possibly related unsolicited adverse events

    Time frame: within 28 days of monoclonal antibody TB31F administration

  3. Occurrence of at least possibly related serious adverse events

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

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

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

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

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

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

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

  7. Accumulation index (Racc) of monoclonal antibody TB31F in serum

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

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

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

  9. 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

    Time frame: day 0 [baseline] & 5

Secondary outcomes

  1. 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.

    Time frame: day 0 [baseline], 1, and 5

  2. 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.

    Time frame: day 0 [baseline], 1, 5, and 14

  3. 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.

    Time frame: day 0 [baseline], 1, and 5

  4. 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.

    Time frame: day 0 [baseline], 1, 5, and 14

  5. 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.

    Time frame: day 0 [baseline], 1, and 5

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

    Time frame: day 0 [baseline], 1, 5, and 14

  7. Participant infection prevalence, assessed by DSF as the proportion of individuals infectious to any number of mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

    Time frame: day 0 [baseline], 1, and 5

  8. Participant infection prevalence, assessed by DMFA as the proportion of individuals infectious to any number of mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.

    Time frame: day 0 [baseline], 1, 5, and 14

  9. Transmission-reducing activity in school-age children and adults, measured as the percent reduction in mean oocyst intensity compared to experimental controls, compared within groups and between groups at all feeding timepoints.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

Other outcomes

  1. Total serum immunoglobulin G level

    Time frame: day 0 [baseline]

    Quantification of the effect of nutritional and protein metabolism status

  2. Serum leptin level

    Time frame: day 0 [baseline]

    Quantification of the effect of nutritional and protein metabolism status

  3. Total protein level

    Time frame: day 0 [baseline]

    Quantification of the effect of nutritional and protein metabolism status

  4. Albumin level

    Time frame: day 0 [baseline]

    Quantification of the effect of nutritional and protein metabolism status

  5. Pre-albumin level

    Time frame: day 0 [baseline]

    Quantification of the effect of nutritional and protein metabolism status

  6. Human genotype analysis at baseline (G6PD, CYP2D6, HBB)

    Time frame: day 0 [baseline]

    To assess human genomic variation in the study population

  7. Plasma biomarkers (i.e. antibodies) at baseline and at post-administration timepoints

    Time frame: day 0 [baseline]

    To assess the presence of plasma biomarkers in the study population

  8. Transmission-blocking activity measured as the percent reduction in mosquito infection prevalence compared to experimental controls, compared within and between groups at all feeding timepoints.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

    To assess the transmission-blocking activity of participant serum after TB31F administration as assessed in the Standard Membrane Feeding Assay (SMFA) at each dose level in adults and school-age children

  9. The concentration of TB31F in serum that provides >80% reduction in the average proportion of infected mosquitoes as measured in direct skin feeding assay after TB31F administration.

    Time frame: day 0 [baseline], 1, and 5.

  10. The concentration of TB31F in serum that provides >80% reduction in the average proportion of infected mosquitoes as measured in direct membrane feeding assays after TB31F administration.

    Time frame: day 0 [baseline], 1, 5, and 14.

  11. The concentration of TB31F in serum that provides >80% transmission blocking activity relative to experimental controls as measured in standard membrane feeding assay after TB31F administration.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

  12. Measure the concentration of TB31F in serum that provides >80% reduction in the average mosquito infection intensity (oocyst number) as measured in direct skin feeding assay after TB31F administration.

    Time frame: day 0 [baseline], 1, and 5.

  13. The concentration of TB31F in serum that provides >80% reduction in the average mosquito infection intensity (oocyst number) as measured in direct membrane feeding assays after TB31F administration.

    Time frame: day 0 [baseline], 1, 5, and 14.

  14. The concentration of TB31F in serum that provides >80% transmission reducing activity relative to experimental controls as measured in standard membrane feeding assay after TB31F administration.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

  15. The correlation between naturally acquired anti-gametocyte immune responses and naturally acquired functional TRA on mosquito infection prevalence, assessed by SMFA and measured as the proportion dissected mosquitoes with any number of oocysts.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

    To assess the impact of naturally acquired TRA, present prior to TB31F administration, on transmission endpoints and TB31F efficacy estimates

  16. The correlation between naturally acquired anti-gametocyte immune responses and naturally acquired functional transmission-reducing activity on mosquito infection intensity, assessed by SMFA and measured as the number of oocysts in dissected mosquitoes.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

    To assess the impact of naturally acquired TRA, present prior to TB31F administration, on transmission endpoints and TB31F efficacy estimates

  17. The correlation between naturally acquired anti-gametocyte immune responses and naturally acquired functional TRA on participant infectivity, assessed by SMFA as the proportion of individuals infectious to any number of mosquitoes.

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

    To assess the impact of naturally acquired TRA, present prior to TB31F administration, on transmission endpoints and TB31F efficacy estimates

  18. Parasite genotype analysis (amplicon and whole genome sequencing)

    Time frame: day 0 [baseline]

    To assess human and parasite genomic variation and association with parasite measures

  19. Antibodies and parasite protein in plasma at baseline and at post-administration timepoints

    Time frame: day 0 [baseline], 5, 14, 28, 56, and 84

    To assess the impact of plasma biomarkers on malaria transmission efficiency

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • London School of Hygiene and Tropical Medicine
  • Malaria Research and Training Center, Bamako, Mali

Registry information

Official study title

A Phase 1/2a Single Centre, Randomised, Placebo-controlled, Double-blind, Dose-escalation, Age De-escalation, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Plasmodium Falciparum Transmission-reducing Activity of Monoclonal Antibody TB31F in Malaria-exposed Malian Adults and Children

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
May 14, 2024
Registry last updated
Jan 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.