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

A Phase 1, Dose Escalation, Double Blind, Placebo Controlled Clinical Trial With Controlled Human Malaria Infections (CHMI) to Evaluate Safety, Tolerability, Pharmacokinetics, and Protective Efficacy of an Anti-Malaria Human Monoclonal Antibody, MAM01, in Healthy, Malaria-Naive Adults

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Biological: MAM01 1.5 mg/kg; Biological: Placebo; Biological: Placebo; Biological: MAM01 5 mg/kg; Biological: MAM01 5 mg/kg; Biological: MAM01 10 mg/kg; Biological: MAM01 40 mg/kg; Biological: MAM01 450 mg; Biological: MAM01 600 mg; Biological: MAM01 900 mg; Other: Control

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Center for Vaccine Development and Global Health, 685 W. Baltimore Street

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: MAM01 1.5 mg/kg; 1.5 mg/kg MAM01 will be administered via IV route.; Biological: Placebo; Placebo will be administered via IV route.; Biological: Placebo; Placebo will be administered via SC route.
Experimental: 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	Biological: Placebo; Placebo will be administered via IV route.; Biological: Placebo; Placebo will be administered via SC route.; Biological: MAM01 5 mg/kg; 5 mg/kg MAM01 will be administered via SC route.; Biological: MAM01 5 mg/kg; 5 mg/kg MAM01 will be administered via IV route.
Experimental: 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.	Biological: Placebo; Placebo will be administered via IV route.; Biological: Placebo; Placebo will be administered via SC route.; Biological: MAM01 5 mg/kg; 5 mg/kg MAM01 will be administered via SC route.; Biological: MAM01 5 mg/kg; 5 mg/kg MAM01 will be administered via IV route.
Experimental: 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.	Biological: Placebo; Placebo will be administered via IV route.; Biological: Placebo; Placebo will be administered via SC route.; Biological: MAM01 10 mg/kg; 10 mg/kg MAM01 will be administered via IV route.
Experimental: 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	Biological: Placebo; Placebo will be administered via IV route.; Biological: Placebo; Placebo will be administered via SC route.; Biological: MAM01 40 mg/kg; 40 mg/kg MAM01 will be administered via IV route.
Experimental: Part A: Multiple Ascending Dose (MAD) (Repeat dosing): MAM01; Participants from Cohort 2 and from Cohort 3 will receive 5 mg/kg MAM01 SC.	Biological: MAM01 5 mg/kg; 5 mg/kg MAM01 will be administered via SC route.; Biological: MAM01 5 mg/kg; 5 mg/kg MAM01 will be administered via IV route.
Experimental: 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).	Biological: MAM01 450 mg; MAM01 will be administered via SC route.
Experimental: 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	Biological: MAM01 600 mg; MAM01 will be administered via SC route.
Experimental: 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.	Biological: MAM01 900 mg; MAM01 will be administered via SC route.
Experimental: 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	Other: Control; No drug or placebo will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Observed Concentration (Cmax) Following Single Dose of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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
Concentration at the Time of CHMI (CCHMI) of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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
Blood Terminal Elimination Rate Constant (λz) of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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
Terminal Half Life (t1/2) Following Single Dose of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	Time Frame: 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
t1/2 Following Repeat Dosing of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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 From Time=0 Extrapolated to Infinity (AUC0-infinity) of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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
Absolute Bioavailability of SC Formulation Following Repeated Dosing of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.	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, 280 and 378 post-dose
Accumulation Ratio (AUC0-168) Following Repeated Doses of MAM01	Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics. The accumulation ratio was calculated as the ratio of AUC (0-168) (post first dose) to AUC (210-378) (post redose).	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 and 168 post-dose
Number of Participants With Confirmed Pf Infection Assessed by Quantitative Polymerase Chain Reaction Assay (qRT-PCR) After CHMI	The characterization of protective efficacy against Pf following CHMI challenge, was assessed by evaluating the presence or absence of Pf infection as determined by qRT-PCR after CHMI (planned through 4 weeks post-CHMI) and evaluating the time to parasitemia after CHMI in each cohort.	Up to Day 27 post-CHMI
Time to Parasitemia After CHMI	Parasitemia was assessed by qRT-PCR up to Day 27 following CHMI. In addition, a thick blood smear was prepared for microscopic analysis, which was examined only once the first qRT-PCR sample tested positive. Daily parasitemia monitoring continued until the participant had a confirmed initial positive qRT-PCR. The first positive qRT-PCR triggered either a second PCR test or microscopic analysis of the blood smear. Once two positive results were obtained, rescue therapy was initiated.	Up to Day 27 post-CHMI
Cohorts 1, 4 and 5: Numbers of Participants With Seroconversion	The formation of ADAs (immunogenicity) following MAM01 SC and/or IV administration) was evaluated by measuring titers of ADA to MAM01 to last study visit for all participants. Capillary blood samples and selected serum samples were collected on volumetric absorptive micro-sampling (VAMS) devices at timepoints.	Up to Day 280
Cohorts 2 and 3: Numbers of Participants Receiving 2 Doses With Seroconversion	The formation of ADAs (immunogenicity) following MAM01 SC and/or IV administration) was evaluated by measuring titers of ADA to MAM01 to last study visit for all participants. Capillary blood samples and selected serum samples were collected on volumetric absorptive micro-sampling (VAMS) devices at timepoints.	Up to Day 378
Cohort 6: Numbers of Participants With Seroconversion	The formation of ADAs (immunogenicity) following MAM01 SC and/or IV administration) was evaluated by measuring titers of ADA to MAM01 to last study visit for all participants. Capillary blood samples and selected serum samples were collected on volumetric absorptive micro-sampling (VAMS) devices at timepoints.	Up to Day 84

Collaborators and Investigators

• Sponsor: Gates Medical Research Institute
• Investigators: Study Director: +1 866 789 5767, Gates Medical Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Actual): December 13, 2024
• Study Completion (Actual): December 13, 2024

Study Registration Dates

• First Submitted: May 26, 2023
• First Submitted That Met QC Criteria: May 26, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Healthy volunteers; First-in-Human; Prevention; Phase 1; Dose-escalation; Mosquito; Multiple ascending dose; Single ascending dose; Malaria vaccine; Recruiting; MAM01 monoclonal antibody; Gates; Nonprofit
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria
• Other Study ID Numbers: Gates MRI-MAM01-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No