Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults

Bill & Melinda Gates Medical Research Institute

Status and phase: Completed; Phase 1

Conditions: Malaria

Treatments: Biological: MAM01 10 mg/kg; Biological: MAM01 1.5 mg/kg; Other: Control; Biological: MAM01 900 mg; Biological: MAM01 450 mg; Biological: MAM01 600 mg; Biological: MAM01 5 mg/kg; Biological: MAM01 40 mg/kg; Biological: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05891236

Gates MRI-MAM01-101

Details and patient eligibility

About

This is a First-in-Human (FiH), randomized, two-part, dose-escalation trial of MAM01 monoclonal antibody (mAb) targeting the Plasmodium falciparum (Pf) Circumsporozoite Protein (CSP). This study will evaluate the safety, tolerability, pharmacokinetics (PK), and protective efficacy of MAM01, as well as safety and PK of repeat subcutaneous (SC) dosing. Part A will have a double-blind, placebo-controlled design. Part B will randomize participants to one of three open-label MAM01 dose groups; a separate non-randomized group will be enrolled to include participants who will receive no treatment and act as infectivity controls.

Enrollment: 61 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants who are healthy as determined by medical evaluation including medical history, physical examination and laboratory tests

• Body Mass Index (BMI) 18 to 30 kilograms per square meter (kg/m^2) (inclusive) to a maximum of 220 pounds

• Both males and females are eligible to participate as per the following:

  a. Female participants physically capable of pregnancy, have at least one negative pregnancy test during Screening, on the day of enrollment, prior to Investigational product (IP) administration, prior to CHM and at the start of antimalarial treatment, and who agree to use effective contraception to avoid pregnancy from 28 days before enrollment through 10 months after last administration of investigational product are eligible to participate.

• Capable of giving signed Informed Consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and the trial protocol, and completion of a test of understanding if he/she may participate in the CHMI procedure

• Reported completion of primary Coronavirus Disease (COVID) vaccine series is documented

Exclusion criteria

• Acute illness or fever ≥99.5°Fahrenheit (F) (or ≥37.5 degrees Celsius) on day of dosing
• Women who are pregnant or breastfeeding
• Evidence and/or history of clinically significant medical condition(s) as judged by the Investigator, including malignancies, diabetes mellitus, and unstable or uncontrolled hypertension
• A 5-year cardiovascular risk of ≥10% using the Gaziano nomogram
• History of any autoimmune disease or immune deficiency or other impairment to the immune system, including but not limited to Human immunodeficiency virus (HIV), autoimmune conditions or immunosuppressive therapy
• Participation in an interventional clinical trial and/or receipt of any investigational drug within 180 days prior to administration of trial drug on Day 0
• Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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61 participants in 10 patient groups

Part A: Single Ascending Dose (SAD): Dose escalation cohort 1: MAM01 and placebo Intravenous (IV)

Experimental group

Description:

2 sentinel participants will be randomized in a 1:1 ratio to receive MAM01 1.5 milligrams per kilogram (mg/kg) IV or placebo. Following at least a 24-hour safety review period, the 6 remaining participants of Cohort 1 will be randomized in a 5:1 ratio to receive MAM01 1.5 mg/kg IV or placebo.

Treatment:

Biological: Placebo

Biological: Placebo

Biological: MAM01 1.5 mg/kg

Part A: SAD dosing: Dose escalation Cohort 2: MAM01 and placebo SC

Experimental group

Description:

7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg SC or placebo

Treatment:

Biological: Placebo

Biological: Placebo

Biological: MAM01 5 mg/kg

Biological: MAM01 5 mg/kg

Part A: SAD dosing: Dose escalation Cohort 3: MAM01 and placebo IV

Experimental group

Description:

7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg IV or placebo.

Treatment:

Biological: Placebo

Biological: Placebo

Biological: MAM01 5 mg/kg

Biological: MAM01 5 mg/kg

Part A: SAD dosing: Dose escalation Cohort 4: MAM01 and placebo IV

Experimental group

Description:

8 participants will be randomly assigned in a 6:2 ratio to receive MAM01 10 mg/kg IV or placebo.

Treatment:

Biological: Placebo

Biological: Placebo

Biological: MAM01 10 mg/kg

Part A: SAD dosing: Dose escalation Cohort 5: MAM01 and placebo IV

Experimental group

Description:

7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 40 mg/kg IV or placebo

Treatment:

Biological: Placebo

Biological: Placebo

Biological: MAM01 40 mg/kg

Part A: Multiple Ascending Dose (MAD) (Repeat dosing): MAM01

Experimental group

Description:

Participants from Cohort 2 and from Cohort 3 will receive 5 mg/kg MAM01 SC.

Treatment:

Biological: MAM01 5 mg/kg

Biological: MAM01 5 mg/kg

Part B: Dose Expansion Cohort 6: Group 1: MAM01

Experimental group

Description:

6 participants will receive a 450 mg SC dose of MAM01. The dose was selected by applying a PK-pharmacodynamic (PD) model from the Part A data to estimate a (data-driven) protection threshold at Controlled Human Malaria Infection (CHMI).

Treatment:

Biological: MAM01 450 mg

Part B: Dose Expansion Cohort 6: Group 2: MAM01

Experimental group

Description:

8 participants will receive a 600 mg SC dose of MAM01. The dose was selected by applying a PK-PD model from the Part A data to estimate a (data-driven) protection threshold at CHMI

Treatment:

Biological: MAM01 600 mg

Part B: Dose Expansion Cohort 6: Group 3: MAM01

Experimental group

Description:

8 participants will receive 900 mg SC dose of MAM01. The dose was selected by applying a PK-PD model from the Part A data to estimate a (data-driven) protection threshold at CHMI.

Treatment:

Biological: MAM01 900 mg

Internal Infectivity Controls

Experimental group

Description:

6 participants will be enrolled into a non-randomized group prior to CHMI. These participants will receive no treatment and act as infectivity controls

Treatment:

Other: Control