Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population

A Phase 1b, Age De-Escalation/Dose Escalation Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in an African Population of Adults and Children in a Setting of Perennial Malaria Transmission

This study will test a new drug (MAM01) to find which doses are safe and could help prevent people from getting malaria for at least 4 months. The study will take place in parts of Africa where malaria is common. Part A is an open-label study conducted in healthy adults whereas Part B is double-blind study conducted in young children and infants. Both the parts will evaluate the safety, tolerability and pharmacokinetics of MAM01.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: MAM01 300 mg SC; Drug: Placebo SC; Drug: MAM01 300 mg IM; Drug: Placebo IM; Drug: MAM01 150 mg SC; Drug: MAM01 225 mg SC; Drug: MAM01 150 mg IM; Drug: MAM01 150 mg IV; Drug: MAM01 2000 mg IV; Drug: MAM01 190 mg SC; Drug: Placebo IV

Detailed Description

This is a Phase 1b, age de-escalation/dose escalation trial that will be conducted in a setting of perennial Plasmodium falciparum (malaria parasite) transmission in Africa. The study will be conducted in 2 parts: Part A (Dose Escalation in Adults); Part B (Age De-escalation/Dose Escalation in Younger Children and infants).

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 1

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda, 10005
    • JCRC-Joint Clinical Research Centre
  • Tororo, Uganda, 749
    • IDRC-Infectious Disease Research Collaboration, IDRC Tororo Hospital Station Road

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

PART A

• Male or female adults aged 18 to 55 years inclusive at the time of signing the informed consent form (ICF), who are capable of, and willing to provide, informed consent
• Healthy, as determined by Investigator assessment, including medical history, physical examination, and screening laboratory results
• All dosing groups: hemoglobin level ≥ 8 grams per deciliter (g/dL)
• All dosing groups: living within local jurisdiction of trial site(s) and available for the duration of the trial for all cohorts
• Female participants of childbearing potential must be nonpregnant and agree to avoid becoming pregnant by using an acceptable contraception method

PART B

• Age Cohort 2: male or female children aged 2 years to <5 years at the time their parent or Legally Authorized Representative (LAR) signs the ICF
• Age Cohort 3: male or female children aged 12 months to <24 months at the time their parent or LAR signs the ICF
• Age Cohort 4: male or female infant children aged 3 months to <12 months and weighing at least 5 kilograms (kg) at the time their parent or LAR signs the ICF
• Healthy, as determined by Investigator assessment, including medical history, physical examination, and screening laboratory results
• Hemoglobin level ≥ 8g/dL
• Height and weight Z-scores ≥-2
• Living within local jurisdiction of trial site(s) and available for the duration of the trial

Exclusion Criteria:

PART A & PART B

• Within 48 hours prior to randomization, acute febrile illness

  • Sickle cell disease or history of splenectomy
  • Use of antimalarial chemoprevention or treatment, and/or antibiotics with known antimalarial effects (eg, clotrimoxazole, azithromycin, tetracyclines) within 30 days prior to dosing
  • Enrolled in another clinical trial within 90 days prior to Screening or planning to participate in another trial during, or within 1 year following, their participation in this trial
  • Received any doses of a malaria vaccine or other monoclonal antibodies (mAb) to Pf
  • Eligible to receive a malaria vaccine (RTS, S/AS01 or R21/Matrix-M) at screening or if it is expected to become available during the period of the trial.
  • History of allergy or hypersensitivity or contraindications to trial drugs (including those used as empirically treatment for Pf to clear any existing parasitemia), excipients or related substances
  • Any history of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the trial
  • History of any autoimmune disease or immunodeficiency or other impairment to the immune system, including HIV infection
  • Use of chronic (≥ 14 days) immunosuppressive agents including systemic steroids (eg, prednisone >10 milligrams per day [mg/day]) within 30 days prior to dosing. Use of inhaled or topical corticosteroids is permitted
  • Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising with blood draws
  • Receipt of immunoglobulins and/or blood products within the past 6 months
  • Any current uncontrolled medical or psychiatric condition, or substance abuse problems that in the opinion of the Investigator, will make it unlikely for participant to comply with the protocol, may interfere with study assessments, or could jeopardize the safety of the participant
  • Any contraindication for a subcutaneous injection, intravenous injection, or intramuscular injection, as applicable
  • For Part A, female participants who are breastfeeding, pregnant, or unable or unwilling to adhere to required contraception
  • For Part B, in the opinion of the Investigator, the parent or LAR may not be able to ensure participant compliance with the requirements of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Cohort 1a (Healthy Adults): 300 milligrams (mg) MAM01 subcutaneously (SC); Participants will receive MAM01.	Drug: MAM01 300 mg SC; MAM01 300 mg will be administered SC
Experimental: Part A: Cohort 1b (Healthy Adults): 300 mg MAM01 intramuscularly (IM); Participants will receive MAM01.	Drug: MAM01 300 mg IM; MAM01 300 mg will be administered IM route
Experimental: Part A: Cohort 1c (Healthy Adults): 2000 mg MAM01 intravenously (IV); Participants will receive MAM01.	Drug: MAM01 2000 mg IV; MAM01 2000 mg will be administered IV
Experimental: Part B: Cohort 2a (Healthy Younger Children): 190 mg MAM01 or placebo SC; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: Placebo SC; Placebo will be administered SC; Drug: MAM01 190 mg SC; MAM01 190 mg will be administered SC
Experimental: Part B: Cohort 2b (Healthy Younger Children): 225 mg MAM01 or placebo SC; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: Placebo SC; Placebo will be administered SC; Drug: MAM01 225 mg SC; MAM01 225 mg will be administered SC
Experimental: Part B: Cohort 3a (Healthy Infants): 150 mg MAM01 or placebo SC; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: Placebo SC; Placebo will be administered SC; Drug: MAM01 150 mg SC; MAM01 150 mg will be administered SC
Experimental: Part B: Cohort 3b (Healthy Infants): 150 mg MAM01 or placebo IM; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: Placebo IM; Placebo will be administered IM; Drug: MAM01 150 mg IM; MAM01 150 mg will be administered IM
Experimental: Part B: Cohort 3c (Healthy Infants): 150 mg MAM01 or placebo IV; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: MAM01 150 mg IV; MAM01 150 mg will be administered IV; Drug: Placebo IV; Placebo will be administered IV.
Experimental: Part B: Cohort 4a (Healthy Infants): 150 mg MAM01 or placebo SC; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: Placebo SC; Placebo will be administered SC; Drug: MAM01 150 mg SC; MAM01 150 mg will be administered SC
Experimental: Part B: Cohort 4b (Healthy Infants): 150 mg MAM01 or placebo IM; Participants will be randomized in 3:1 ratio (MAM01 : PBO)	Drug: Placebo IM; Placebo will be administered IM; Drug: MAM01 150 mg IM; MAM01 150 mg will be administered IM
Experimental: Part B: Cohort 4c (Healthy Infants): 150 mg MAM01 or placebo IV; Participants will be randomized in 3:1 ratio (MAM01: PBO)	Drug: MAM01 150 mg IV; MAM01 150 mg will be administered IV; Drug: Placebo IV; Placebo will be administered IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants reporting solicited systemic AEs and solicited injection site AEs (applicable to IM dosing)	Up to 7 days post dose
Number of participants reporting solicited systemic AEs and solicited injection site AEs (applicable to SC dosing)	Up to 7 days post dose
Number of participants reporting Treatment-emergent adverse events (TEAEs)	Up to 28 days post dose (Part A and B)
Number of participants reporting serious adverse events (SAEs), adverse events of special interest (AESI), and AEs leading to discontinuation	Up to 182 days post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with graded abnormal clinical hematology and chemistry laboratory results		Up to 28 days post dose
Maximal observed blood concentration of MAM01 following the first dose (Cmax1)	Capillary blood samples will be collected for the analysis pharmacokinetic parameters. Blood concentrations of MAM01 will be measured using a validated immunoassay.	Pre- and post-dose (IV dosing groups only) at Day 1, 4, 7, 14, 28, 56, 84, 112, 140, and 182
Concentration at Day 182 (C182)		At Day 182 post first dose
Total Area Under the Concentration Curve (AUC) Day 0 - Day 182		From 0 to 182 days post dose
Percentage of participants with antidrug antibodies (ADAs) to MAM01		At Days 1, 28, 84, and 182

Collaborators and Investigators

• Sponsor: Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2025
• Primary Completion (Actual): May 28, 2026
• Study Completion (Actual): May 28, 2026

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Malaria; Plasmodium falciparum; Pediatric; Prevention; Antibody; Dose Escalation; Monoclonal; MAM01; De-Escalation; Perennial Malaria Transmission; mAb-1797
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum
• Other Study ID Numbers: Gates MRI-MAM01-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD data that underlie the results presented herein
• IPD Sharing Time Frame: Within 12 months of the study completion date
• IPD Sharing Access Criteria: Anonymized participant-level data may be shared with external researchers in accordance with trial participants' written and executed informed consent and applicable local regulations. Qualified researchers may submit a request along with a research proposal to Gates MRI for review. A data sharing agreement must be in place before any clinical trial data are shared. Additional restrictions may apply due to contractual obligations or regulatory constraints.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No