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

Radboud University Medical Center

Status and phase: Completed; Phase 2; Phase 1

Conditions: Malaria,Falciparum

Treatments: Other: Normal saline; Drug: TB31F

Study type: Interventional

Funder types: Other

Identifiers

NCT06413108

TB31F Mali

Details and patient eligibility

About

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.

Enrollment: 167 patients

Sex: All

Ages: 10 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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167 participants in 13 patient groups, including a placebo group

1A: control

Placebo Comparator group

Description:

0.2 mL normal saline

Treatment:

Other: Normal saline

1B: 10 mg TB31F

Experimental group

Description:

0.2 mL (10 mg) TB31F

Treatment:

Drug: TB31F

2A: control

Placebo Comparator group

Description:

2 mL normal saline

Treatment:

Other: Normal saline

2B:100 mg TB31F

Experimental group

Description:

2 mL (100 mg) TB31F

Treatment:

Drug: TB31F

3A: control

Placebo Comparator group

Description:

4 mL normal saline

Treatment:

Other: Normal saline

3B: 200 mg TB31F

Experimental group

Description:

4 mL (200 mg) TB31F

Treatment:

Drug: TB31F

4A: control

Placebo Comparator group

Description:

0.2 mL normal saline

Treatment:

Other: Normal saline

4B: 10 mg TB31F

Experimental group

Description:

0.2 mL (10 mg) TB31F

Treatment:

Drug: TB31F

5A: control

Placebo Comparator group

Description:

2.0 mL normal saline

Treatment:

Other: Normal saline

5B: 100 mg TB31F

Experimental group

Description:

2.0 mL (100 mg) TB31F

Treatment:

Drug: TB31F

6A: control

Placebo Comparator group

Description:

0.6 or 2.0 mL normal saline

Treatment:

Other: Normal saline

6B: 30 mg TB31F

Experimental group

Description:

0.6 mL (30 mg) TB31F

Treatment:

Drug: TB31F

6C: 100 mg TB31F

Experimental group

Description:

2.0 mL (100 mg) TB31F

Treatment:

Drug: TB31F