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

Malaria,Falciparum Clinical Trial

Official 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06413108
• Other study ID #: TB31F Mali
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2024
• Est. completion date: January 2025

Study information

• Verified date: May 2024
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 165
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 50 Years

Eligibility

SAFETY COHORT (STUDY ARM 1-5)

Inclusion Criteria:

1. Written/signed informed consent

2. Adult cohorts: 18-50 years of age

3. School-age children cohorts: 10-15 years of age

4. Haemoglobin =10 g/dL

5. Non-lactating females of childbearing potential agree to the use of continuous adequate contraception for 28 days after having received investigational product

6. Subject agrees to refrain from blood donation during the study and for 5 months after having received investigational product

7. Subjects are available to attend all study visits

8. In opinion of the investigator, the subject can and will comply with the requirements of the protocol

Exclusion Criteria:

1. Women who are pregnant (tested at baseline and at day 28 after administration of investigational product by urine and/or serum pregnancy testing (ß-hCG)) or lactating

2. Symptomatic malaria

3. Current acute or chronic disease, including clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history or physical examination

4. Clinically significant abnormal blood chemistries and haematology

5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 year

6. History of adverse reactions to monoclonal antibodies

7. 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

8. 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:

1. Written/signed informed consent

2. 10-50 years of age

3. Haemoglobin =10 g/dL

4. Non-lactating females of childbearing potential agree to the use of continuous adequate contraception for 28 days after having received investigational product

5. Subject agrees to refrain from blood donation during the study and for 5 months after having received investigational product

6. Subjects are available to attend all study visits

7. In opinion of the investigator, the subject can and will comply with the requirements of the protocol

8. Asymptomatic P. falciparum mono-infection with asexual parasite densities <3000 parasites/µL

9. Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/µL

Exclusion Criteria:

1. Women who are pregnant (tested at baseline and at day 28 after administration of investigational product by urine and/or serum pregnancy testing (ß-hCG)) or lactating

2. Symptomatic malaria

3. Current acute or chronic disease, including clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history or physical examination

4. Clinically significant abnormal blood chemistries and haematology

5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years

6. History of adverse reactions to monoclonal antibodies

7. 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

8. 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

9. Use of anti-malarial drug treatment in the last 14 days

10. Prior receipt of an antimalarial monoclonal antibody

11. Prior receipt of a P. falciparum transmission-blocking vaccine

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Malaria,Falciparum

Intervention

Drug:
• TB31F
transmission-blocking monoclonal antibody TB31F

Other:
• Normal saline
normal saline as control (placebo)

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University Medical Center	London School of Hygiene and Tropical Medicine, Malaria Research and Training Center, Bamako, Mali

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total serum immunoglobulin G level	Quantification of the effect of nutritional and protein metabolism status	day 0 [baseline]
Other	Serum leptin level	Quantification of the effect of nutritional and protein metabolism status	day 0 [baseline]
Other	Total protein level	Quantification of the effect of nutritional and protein metabolism status	day 0 [baseline]
Other	Albumin level	Quantification of the effect of nutritional and protein metabolism status	day 0 [baseline]
Other	Pre-albumin level	Quantification of the effect of nutritional and protein metabolism status	day 0 [baseline]
Other	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.	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	day 0 [baseline], 5, 14, 28, 56, and 84
Other	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.		day 0 [baseline], 1, and 5.
Other	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.		day 0 [baseline], 1, 5, and 14.
Other	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.		day 0 [baseline], 5, 14, 28, 56, and 84
Other	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.		day 0 [baseline], 1, and 5.
Other	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.		day 0 [baseline], 1, 5, and 14.
Other	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.		day 0 [baseline], 5, 14, 28, 56, and 84
Primary	Occurrence of at least possibly related solicited local and systemic adverse events		within 7 days of monoclonal antibody TB31F administration
Primary	Occurrence of at least possibly related unsolicited adverse events		within 28 days of monoclonal antibody TB31F administration
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	Area under the serum concentration-time curve (AUC0-t, 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.
Primary	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	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
Secondary	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
Secondary	Mosquito infection prevalence, assessed by direct skin feed 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, and 5
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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