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

NCT05891236 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Gates MRI-MAM01-101
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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

Keywords

Healthy volunteers; MAM01 monoclonal antibody; First-in-Human; Dose-escalation; Single ascending dose; Multiple ascending dose; Recruiting; Malaria vaccine; Mosquito; Gates; Prevention; Phase 1; Nonprofit

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Solicited Adverse Events (AEs) in the Subcutaneous Cohorts

  Solicited AEs were defined events participants were specifically asked about, which were recorded by participants in the memory aid card. Solicited AES included local injection site AEs (pain, redness, swelling, itching and bruising) and systemic AEs (fever, chills, headache, fatigue, nausea, muscle pain and joint pain). A Solicited AE does not necessarily have a causal relationship with the intervention.

  Day 1 to Day 7 post dose

• Number of Participants Reporting Unsolicited Adverse Events

  In this study an unsolicited AE is any AE not captured as a solicited AE in the Memory Aid Card between Day 0 and Day 7 after MAM01 dosing, and all AEs occurring after Day 7 post dose were collected as Unsolicited AEs.

  Through Day 28 post dose

• Number of Participants Reporting Serious Adverse Events (SAEs) Including Suspected Unexpected Serious Adverse Reactions (SUSARs) and Adverse Events Special Interest (AESIs)

  A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is a medically significant / important event or reaction. SUSARs are AEs reported for a clinical trial participant, which is assessed by the Sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug. AESIs are adverse events that the Sponsor wants to monitor closely and which require expedited reporting.

  Up to Day 168

• Number of Participants Who Received 2 Doses Reporting SUSARs, SAEs and AESIs

  A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is a medically significant / important event or reaction. SUSARs are AEs reported for a clinical trial participant, which is assessed by the Sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug. AESIs are adverse events that the Sponsor wants to monitor closely and which require expedited reporting.

  Through Day 336

• Number of Participants With Clinically Significant Changes in Serum Chemistry Parameters

  Blood samples were collected for the assessment of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total carbon-dioxide (CO2), chloride, total bilirubin, creatinine, blood urea nitrogen, glucose, albumin, total protein, sodium and potassium.

  Through Day 336

• Number of Participants With Clinically Significant Changes in Hematology Parameters

  Blood samples were collected for the assessment of complete blood count (CBC) including hemoglobin, platelet count, and white blood cell counts, and differential to include the absolute counts for neutrophils, lymphocytes, eosinophils, and monocytes.

  Through Day 336

Secondary Outcomes (17)

• Maximal Observed Concentration (Cmax) Following Single Dose of MAM01

  Pre-dose, Day 0: end of infusion (EOI), 1, 3 and 6 hours; Day 1: 24 hours; Day 2: 48 hours; Days 7, 14, 28, 42, 56, 70, 84, 98, 112, 140, 168, 224 and 280 post-dose

• Cmax Following Repeat Dosing of MAM01

  Pre-dose, Day 0: end of infusion (EOI), 1, 3 and 6 hours, Day 1: 24 hours, Day 2: 48 hours, Days 7, 14, 28, 42, 56, 70, 84, 98, 112, 140, 168, 224 and 280 post-dose

• Area Under the Curve (AUC) From Time=0 to the Last Measurable Concentration (AUC0-t) Following Single Dose of MAM01

  Pre-dose, Day 0: end of infusion (EOI), 1, 3 and 6 hours; Day 1: 24 hours; Day 2: 48 hours; Days 7, 14, 28, 42, 56, 70, 84, 98, 112, 140, 168, 224 and 280 post-dose

• AUC (0-t) Following Repeat Dosing of MAM01

  Pre-dose, Day 0: end of infusion (EOI), 1, 3 and 6 hours; Day 1: 24 hours; Day 2: 48 hours; Days 7, 14, 28, 42, 56, 70, 84, 98, 112, 140, 168, 224 and 280 post-dose

• Partial AUC's Time= 0 to the CHMI Challenge (AUC0-CHMI) of MAM01

  Pre-dose, Day 0: end of infusion (EOI), 1, 3 and 6 hours; Day 1: 24 hours; Day 2: 48 hours; Days 7, 14, 28, 42, 56, 70, 84, 98, 112, 140, 168, 224 and 280 post-dose

Study Arms (10)

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

EXPERIMENTAL

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.

Biological: MAM01 1.5 mg/kg; Biological: Placebo

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

EXPERIMENTAL

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

Biological: MAM01 5 mg/kg; Biological: Placebo

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

EXPERIMENTAL

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

Biological: Placebo; Biological: MAM01 5 mg/kg

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

EXPERIMENTAL

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

Biological: Placebo; Biological: MAM01 10 mg/kg

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

EXPERIMENTAL

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

Biological: Placebo; Biological: MAM01 40 mg/kg

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

EXPERIMENTAL

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

Biological: MAM01 5 mg/kg

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

EXPERIMENTAL

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).

Biological: MAM01 450 mg

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

EXPERIMENTAL

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

Biological: MAM01 600 mg

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

EXPERIMENTAL

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.

Biological: MAM01 900 mg

Internal Infectivity Controls

EXPERIMENTAL

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

Other: Control

Interventions

MAM01 1.5 mg/kg BIOLOGICAL

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

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

Placebo BIOLOGICAL

Placebo will be administered via IV route.

Part A: SAD dosing: Dose escalation Cohort 3: MAM01 and placebo IV; Part A: SAD dosing: Dose escalation Cohort 4: MAM01 and placebo IV; Part A: SAD dosing: Dose escalation Cohort 5: MAM01 and placebo IV; Part A: Single Ascending Dose (SAD): Dose escalation cohort 1: MAM01 and placebo Intravenous (IV)

MAM01 5 mg/kg BIOLOGICAL

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

Part A: Multiple Ascending Dose (MAD) (Repeat dosing): MAM01; Part A: SAD dosing: Dose escalation Cohort 2: MAM01 and placebo SC

MAM01 10 mg/kg BIOLOGICAL

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

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

MAM01 40 mg/kg BIOLOGICAL

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

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

MAM01 450 mg BIOLOGICAL

MAM01 will be administered via SC route.

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

Control OTHER

No drug or placebo will be administered.

Internal Infectivity Controls

MAM01 600 mg BIOLOGICAL

MAM01 will be administered via SC route.

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

MAM01 900 mg BIOLOGICAL

MAM01 will be administered via SC route.

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gates Medical Research Institute: lead

Study Sites (1)

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

Baltimore, Maryland, 21201, United States

Location

Related Publications (1)

• 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. 2026 Feb;26(2):170-181. doi: 10.1016/S1473-3099(25)00481-5. Epub 2025 Sep 23.

  PMID: 41005346 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Study Director
• Organization: Gates MRI

clinical.trials@gatesmri.org

18577022108

Study Officials

• +1 866 789 5767

  Gates Medical Research Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 6, 2023
• Study Start: August 14, 2023
• Primary Completion: December 13, 2024
• Study Completion: December 13, 2024
• Last Updated: June 12, 2026
• Results First Posted: June 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)