A Phase 1b, Age De-Escalation/Dose Escalation Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of MAM01 in Adults, Children, and Special Pediatric Populations in a Setting of Perennial Malaria Transmission in Africa

Gates MRI-MAM01-103

This study will test a new drug (MAM01) to find which doses are safe and could help prevent people from getting malaria. The study will take place in parts of Africa where malaria is common. Parts A and B of the study will first test single doses of MAM01 in healthy adults, then after safety review, in older children, and then after additional safety review, in infants. Part C will then test single doses of MAM01 in children and infants who have a medical problem that could put them at greater risk if they get malaria.

2024-09-01

2026-05-01

2026-05-01

Not yet recruiting

Early phase I

264

Inclusion Criteria: PART A * Age Cohort 1: 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 * Age Cohort 2: male or female children aged 5 to 10 years inclusive at the time their parent or Legally Acceptable Representative (LAR) signs the ICF, and they sign the assent form * 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 * Age Cohort 1: female participants of childbearing potential must be nonpregnant and agree to avoid becoming pregnant by using an acceptable contraception method * Age Cohort 2: height and weight Z-scores ≥-2 * Age Cohort 2: female participants must be pre-menarche PART B * Age Cohort 3: male or female children aged 12 months to \<5 years at the time their parent or LAR signs the ICF * Age Cohort 4: male or female infant children aged 3 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 * All dosing groups: hemoglobin level ≥ 8g/dL * All dosing groups: height and weight Z-scores ≥-2 * All dosing groups: living within local jurisdiction of trial site(s) and available for the duration of the trial PART C - All Participants * Male or female children aged 3 months to \<5 years at the time their parent or LAR signs the ICF * All dosing groups: living within local jurisdiction of trial site(s) and available for the duration of the trial Dosing Group 5a -Severe Anemia * Current or recent (\< 14 days prior) hospitalization for severe anemia (hemoglobin \< 5 g/dL) * Blood transfusions (if required) completed prior to investigational product (IP) administration * Completed, undergoing, or prescribed a course of oral antimalarial treatment as part of anemia management Dosing Group 5b -Severe Acute Malnutrition * Diagnosis of severe acute malnutrition based on: 1. Weight-for-height z-score \<-3; or 2. Mid-upper-arm circumference measurements (\<11.5 centimeters \[cm\] for children aged \>6 months and \<11 cm for infants aged 3-5 months); or 3. Presence of kwashiorkor (edematous malnutrition). * Had completed the stabilization phase of treatment in the hospital for severe acute malnutrition or direct enrollment in an outpatient therapeutic care (OTC) program Dosing Group 5c -Human immunodeficiency virus (HIV) Infection * HIV positive by serology or HIV rapid test or history of positive viral load for HIV * HIV treated by antiretroviral therapy for at least 3 months Dosing Group 5d -Sickle Cell Disease * Sickle cell disease, including hemoglobin SS, hemoglobin SC, and sickle-beta thalassemia confirmed by hemoglobin electrophoresis at Screening * On stable disease-modifying regimen (eg, hydroxyurea) for at least 4 weeks 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) in their catchment area when it is available * 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 (Age Cohort 1) female participants who are breastfeeding, pregnant, or unable or unwilling to adhere to required contraception * For Part A (Age Cohort 2) and 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 PART C - All Participants * Within 48 hours prior to randomization, acute febrile illness * 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 mAb to Pf * Eligible to receive a malaria vaccine (RTS,S/AS01 or R21/Matrix-M) in their catchment area when it is available * 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 * Use of chronic (≥ 14 days) immunosuppressive agents including systemic steroids (eg, prednisone \>10 mg/day) within 30 days prior to dosing. Use of inhaled or topical corticosteroids is permitted * Serious comorbidity likely to be associated with mortality unrelated to infection such as severe heart disease or malignancy * Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising with blood draws * Any current uncontrolled medical or psychiatric condition that in the opinion of the Investigator, will make it unlikely for participant or their parent or LAR to comply with the protocol, or may interfere with study assessments, or could jeopardize the safety of the participant * In the opinion of the Investigator, the parent or LAR may not be able to ensure participant compliance with the requirements of the trial Dosing Group 5a - Severe Anemia * Anemia caused by trauma or malignancy * Known sickle cell disease or hemoglobin SS, hemoglobin SC or sickle-beta thalassemia by hemoglobin electrophoresis at Screening * HIV infection * History of any autoimmune disease or immunodeficiency or other impairment to the immune system * Severe acute malnutrition * Any contraindication for an intravenous injection Dosing Group 5b - Severe Acute Malnutrition * Known sickle cell disease or hemoglobin SS, hemoglobin SC or sickle-beta thalassemia by hemoglobin electrophoresis at Screening * HIV infection * History of any autoimmune disease or immunodeficiency or other impairment to the immune system * Severe anemia (Hemoglobin \<5 g/dL or clinical indication for blood transfusion) * Any contraindication for an intramuscular injection Dosing Group 5c -HIV Infection * Acute anti-retroviral syndrome * CD4 count \< 200 cells per cubic milliliters (cells/mm3) * Active opportunistic infection * Hemoglobin \< 8g/dL * Known sickle cell disease or hemoglobin SS, hemoglobin SC, sickle-beta thalassemia by hemoglobin electrophoresis at Screening * Severe acute malnutrition * Any contraindication for a subcutaneous injection Dosing Group 5d -Sickle Cell Disease * Acute sickle crisis in previous 2 weeks * Hemoglobin \<5 g/dL or clinical indication for blood transfusion * HIV infection * History of any autoimmune disease or immunodeficiency or other impairment to the immune system * Severe acute malnutrition * Any contraindication for a subcutaneous injection

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'All Part C participants are to receive open label MAM01.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 264, 'type': 'ESTIMATED'}}

2024-05-10