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

NCT ID: NCT05891236

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-14
• Study Completion Date: 2024-12-13

Brief Summary

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

MAM01 1.5 mg/kg

Intervention Type: BIOLOGICAL

1.5 mg/kg MAM01 will be administered via IV route.

Placebo

Intervention Type: BIOLOGICAL

Placebo will be administered via IV route.

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

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

Group Type: EXPERIMENTAL

MAM01 5 mg/kg

Intervention Type: BIOLOGICAL

5 mg/kg MAM01 will be administered via SC route.

Placebo

Intervention Type: BIOLOGICAL

Placebo will be administered via SC route.

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

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: BIOLOGICAL

Placebo will be administered via IV route.

MAM01 5 mg/kg

Intervention Type: BIOLOGICAL

5 mg/kg MAM01 will be administered via IV route.

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

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: BIOLOGICAL

Placebo will be administered via IV route.

MAM01 10 mg/kg

Intervention Type: BIOLOGICAL

10 mg/kg MAM01 will be administered via IV route.

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

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: BIOLOGICAL

Placebo will be administered via IV route.

MAM01 40 mg/kg

Intervention Type: BIOLOGICAL

40 mg/kg MAM01 will be administered via IV route.

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

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

Group Type: EXPERIMENTAL

MAM01 5 mg/kg

Intervention Type: BIOLOGICAL

5 mg/kg MAM01 will be administered via SC route.

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

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).

Group Type: EXPERIMENTAL

MAM01 450 mg

Intervention Type: BIOLOGICAL

MAM01 will be administered via SC route.

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

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

Group Type: EXPERIMENTAL

MAM01 600 mg

Intervention Type: BIOLOGICAL

MAM01 will be administered via SC route.

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

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.

Group Type: EXPERIMENTAL

MAM01 900 mg

Intervention Type: BIOLOGICAL

MAM01 will be administered via SC route.

Internal Infectivity Controls

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

Group Type: EXPERIMENTAL

Control

Intervention Type: OTHER

No drug or placebo will be administered.

Interventions

MAM01 1.5 mg/kg

1.5 mg/kg MAM01 will be administered via IV route.

Intervention Type: BIOLOGICAL

Placebo

Placebo will be administered via IV route.

Intervention Type: BIOLOGICAL

MAM01 5 mg/kg

5 mg/kg MAM01 will be administered via SC route.

Intervention Type: BIOLOGICAL

MAM01 10 mg/kg

10 mg/kg MAM01 will be administered via IV route.

Intervention Type: BIOLOGICAL

MAM01 40 mg/kg

40 mg/kg MAM01 will be administered via IV route.

Intervention Type: BIOLOGICAL

MAM01 450 mg

MAM01 will be administered via SC route.

Intervention Type: BIOLOGICAL

Placebo

Placebo will be administered via SC route.

Intervention Type: BIOLOGICAL

MAM01 5 mg/kg

5 mg/kg MAM01 will be administered via IV route.

Intervention Type: BIOLOGICAL

Control

No drug or placebo will be administered.

Intervention Type: OTHER

MAM01 600 mg

MAM01 will be administered via SC route.

Intervention Type: BIOLOGICAL

MAM01 900 mg

MAM01 will be administered via SC route.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gates Medical Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

+1 866 789 5767

Role: STUDY_DIRECTOR

Gates Medical Research Institute

Locations

Center for Vaccine Development and Global Health, 685 W. Baltimore Street

Baltimore, Maryland, United States

Countries

United States

References

Lyke KE, Berry AA, Laurens MB, Winkler J, Joshi S, Koudjra AR, Butler L, Billingsley PF, Pascini T, Patil A, Sim BKL, Fitzgerald G, Riegel J, Andrews K, Levi M, Anderson AB, Wells CD, Liu H, Huleatt J, Miller RS. Human monoclonal antibody MAM01 for protection against malaria in adults in the USA: a first-in-human, phase 1, dose-escalation, double-blind, placebo-controlled, adaptive trial. Lancet Infect Dis. 2025 Sep 23:S1473-3099(25)00481-5. doi: 10.1016/S1473-3099(25)00481-5. Online ahead of print.

Reference Type: DERIVED

PMID: 41005346 (View on PubMed)

Other Identifiers

Gates MRI-MAM01-101

Identifier Type: -

Identifier Source: org_study_id