Safety, Pharmacokinetics, and Plasmodium Falciparum Transmission-reducing Activity of Monoclonal Antibody TB31F in Mali
Phase 1
Active, not recruiting
- Conditions
- Malaria,Falciparum
- Interventions
- Other: Normal saline
- Registration Number
- NCT06413108
- Lead Sponsor
- Radboud University Medical Center
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 165
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 5A: control Normal saline 2.0 mL normal saline 1A: control Normal saline 0.2 mL normal saline 2A: control Normal saline 2 mL normal saline 2B:100 mg TB31F TB31F 2 mL (100 mg) TB31F 4B: 10 mg TB31F TB31F 0.2 mL (10 mg) TB31F 4A: control Normal saline 0.2 mL normal saline 5B: 100 mg TB31F TB31F 2.0 mL (100 mg) TB31F 3A: control Normal saline 4 mL normal saline 6A: control Normal saline 0.6 or 2.0 mL normal saline 6C: 100 mg TB31F TB31F 2.0 mL (100 mg) TB31F 6B: 30 mg TB31F TB31F 0.6 mL (30 mg) TB31F 1B: 10 mg TB31F TB31F 0.2 mL (10 mg) TB31F 3B: 200 mg TB31F TB31F 4 mL (200 mg) TB31F
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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. day 0 [baseline], 1, 5, and 14 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. day 0 [baseline], 1, and 5 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. day 0 [baseline], 1, 5, and 14 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. day 0 [baseline], 5, 14, 28, 56, and 84
Trial Locations
- Locations (1)
Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of Bamako
🇲🇱Bamako, Point G, Mali