## Protocol Section
### Identification Module
**NCT ID:** NCT06413108

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

**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

#### Organization Study ID Info
**ID:** TB31F Mali
#### Organization
**Class:** OTHER
**Full Name:** Radboud University Medical Center
### Status Module
#### Completion Date
**Date:** 2025-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-08

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-03
**Study First Submit QC Date:** 2024-05-08
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Malaria Research and Training Center, Bamako, Mali

**Class:** OTHER

**Name:** London School of Hygiene and Tropical Medicine

#### Lead Sponsor

**Class:** OTHER

**Name:** Radboud University Medical Center

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Malaria,Falciparum

**Keywords:**

- transmission-reducing

- monoclonal antibody

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** SEQUENTIAL

**Intervention Model Description:** We will perform two sequential stages of clinical research, each recruiting a distinct cohort of participants to confirm: 1. TB31F safety and 2. TB31F efficacy. The safety cohort will be composed of the three dose groups in adults (groups 1, 2 and 3) and two dose groups in children (groups 4 and 5). The efficacy cohort will be composed of two dose groups in adults and children (group 6). Participants will be randomised within each treatment group to receive a single sub-cutaneous dose of TB31F or placebo.

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** This is a double-blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded. The study pharmacist will be unblinded and responsible for randomisation and treatment preparation. Entomology staff involved in the mosquito feeding assays will be blinded for the parasitology results.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 165

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 0.2 mL normal saline

**Intervention Names:**

- Other: Normal saline

**Label:** 1A: control

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** 0.2 mL (10 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 1B: 10 mg TB31F

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** 2 mL normal saline

**Intervention Names:**

- Other: Normal saline

**Label:** 2A: control

**Type:** PLACEBO_COMPARATOR

#### Arm Group 4

**Description:** 2 mL (100 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 2B:100 mg TB31F

**Type:** EXPERIMENTAL

#### Arm Group 5

**Description:** 4 mL normal saline

**Intervention Names:**

- Other: Normal saline

**Label:** 3A: control

**Type:** PLACEBO_COMPARATOR

#### Arm Group 6

**Description:** 4 mL (200 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 3B: 200 mg TB31F

**Type:** EXPERIMENTAL

#### Arm Group 7

**Description:** 0.2 mL normal saline

**Intervention Names:**

- Other: Normal saline

**Label:** 4A: control

**Type:** PLACEBO_COMPARATOR

#### Arm Group 8

**Description:** 0.2 mL (10 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 4B: 10 mg TB31F

**Type:** EXPERIMENTAL

#### Arm Group 9

**Description:** 2.0 mL normal saline

**Intervention Names:**

- Other: Normal saline

**Label:** 5A: control

**Type:** PLACEBO_COMPARATOR

#### Arm Group 10

**Description:** 2.0 mL (100 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 5B: 100 mg TB31F

**Type:** EXPERIMENTAL

#### Arm Group 11

**Description:** 0.6 or 2.0 mL normal saline

**Intervention Names:**

- Other: Normal saline

**Label:** 6A: control

**Type:** PLACEBO_COMPARATOR

#### Arm Group 12

**Description:** 0.6 mL (30 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 6B: 30 mg TB31F

**Type:** EXPERIMENTAL

#### Arm Group 13

**Description:** 2.0 mL (100 mg) TB31F

**Intervention Names:**

- Drug: TB31F

**Label:** 6C: 100 mg TB31F

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 1B: 10 mg TB31F

- 2B:100 mg TB31F

- 3B: 200 mg TB31F

- 4B: 10 mg TB31F

- 5B: 100 mg TB31F

- 6B: 30 mg TB31F

- 6C: 100 mg TB31F

**Description:** transmission-blocking monoclonal antibody TB31F

**Name:** TB31F

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- 1A: control

- 2A: control

- 3A: control

- 4A: control

- 5A: control

- 6A: control

**Description:** normal saline as control (placebo)

**Name:** Normal saline

**Type:** OTHER

### Outcomes Module

#### Other Outcomes

**Description:** Quantification of the effect of nutritional and protein metabolism status

**Measure:** Total serum immunoglobulin G level

**Time Frame:** day 0 [baseline]

**Description:** Quantification of the effect of nutritional and protein metabolism status

**Measure:** Serum leptin level

**Time Frame:** day 0 [baseline]

**Description:** Quantification of the effect of nutritional and protein metabolism status

**Measure:** Total protein level

**Time Frame:** day 0 [baseline]

**Description:** Quantification of the effect of nutritional and protein metabolism status

**Measure:** Albumin level

**Time Frame:** day 0 [baseline]

**Description:** Quantification of the effect of nutritional and protein metabolism status

**Measure:** Pre-albumin level

**Time Frame:** day 0 [baseline]

**Description:** 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

**Measure:** 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

**Measure:** 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.

**Measure:** 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.

**Measure:** 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

**Measure:** 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.

**Measure:** 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.

**Measure:** 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

#### Primary Outcomes

**Measure:** Occurrence of at least possibly related solicited local and systemic adverse events

**Time Frame:** within 7 days of monoclonal antibody TB31F administration

**Measure:** Occurrence of at least possibly related unsolicited adverse events

**Time Frame:** within 28 days of monoclonal antibody TB31F administration

**Measure:** 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.

**Measure:** 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.

**Measure:** 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.

**Measure:** 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.

**Measure:** 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.

**Measure:** 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

**Measure:** 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

**Measure:** 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

**Measure:** 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.

**Time Frame:** day 0 [baseline], 1, and 5

**Measure:** 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

**Measure:** 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

**Measure:** 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

**Measure:** 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

**Measure:** 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

**Measure:** 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

### Eligibility Module

**Eligibility 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

**Healthy Volunteers:** True

**Maximum Age:** 50 Years

**Minimum Age:** 10 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### IPD Sharing Statement Module

**Info Types:**

- SAP

- ICF

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000011528

- Term: Protozoan Infections

- ID: D000010272

- Term: Parasitic Diseases

- ID: D000007239

- Term: Infections

- ID: D000096724

- Term: Mosquito-Borne Diseases

- ID: D000079426

- Term: Vector Borne Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11280

- Name: Malaria

- Relevance: HIGH

- As Found: Malaria

- ID: M19133

- Name: Malaria, Falciparum

- Relevance: HIGH

- As Found: Malaria,Falciparum

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14388

- Name: Protozoan Infections

- Relevance: LOW

- As Found: Unknown

- ID: M13185

- Name: Parasitic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M3255

- Name: Mosquito-Borne Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2054

- Name: Vector Borne Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3571

- Name: Malaria

- Relevance: HIGH

- As Found: Malaria

### Condition Browse Module - Meshes

- ID: D000008288

- Term: Malaria

- ID: D000016778

- Term: Malaria, Falciparum

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M4230

- Name: Antibodies, Monoclonal

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
