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

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

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.

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 (β-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 (β-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