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

Gates Medical Research Institute

Status and phase: Enrolling; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: MAM01 300 mg IM; Drug: MAM01 190 mg SC; Drug: MAM01 150 mg SC; Drug: MAM01 2000 mg IV; Drug: Placebo IM; Drug: MAM01 300 mg SC; Drug: Placebo SC; Drug: MAM01 150 mg IV; Drug: MAM01 225 mg SC; Drug: Placebo IV; Drug: MAM01 150 mg IM

Study type: Interventional

Funder types: Other

Identifiers

NCT06408857

Gates MRI-MAM01-103

Details and patient eligibility

About

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.

Full 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).

Enrollment: 123 estimated patients

Sex: All

Ages: 3 months to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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123 participants in 11 patient groups

Part A: Cohort 1a (Healthy Adults): 300 milligrams (mg) MAM01 subcutaneously (SC)

Experimental group

Description:

Participants will receive MAM01.

Treatment:

Drug: MAM01 300 mg SC

Part A: Cohort 1b (Healthy Adults): 300 mg MAM01 intramuscularly (IM)

Experimental group

Description:

Participants will receive MAM01.

Treatment:

Drug: MAM01 300 mg IM

Part A: Cohort 1c (Healthy Adults): 2000 mg MAM01 intravenously (IV)

Experimental group

Description:

Participants will receive MAM01.

Treatment:

Drug: MAM01 2000 mg IV

Part B: Cohort 2a (Healthy Younger Children): 190 mg MAM01 or placebo SC

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: Placebo SC

Drug: MAM01 190 mg SC

Part B: Cohort 2b (Healthy Younger Children): 225 mg MAM01 or placebo SC

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: MAM01 225 mg SC

Drug: Placebo SC

Part B: Cohort 3a (Healthy Infants): 150 mg MAM01 or placebo SC

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: Placebo SC

Drug: MAM01 150 mg SC

Part B: Cohort 3b (Healthy Infants): 150 mg MAM01 or placebo IM

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: MAM01 150 mg IM

Drug: Placebo IM

Part B: Cohort 3c (Healthy Infants): 150 mg MAM01 or placebo IV

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: Placebo IV

Drug: MAM01 150 mg IV

Part B: Cohort 4a (Healthy Infants): 150 mg MAM01 or placebo SC

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: Placebo SC

Drug: MAM01 150 mg SC

Part B: Cohort 4b (Healthy Infants): 150 mg MAM01 or placebo IM

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01 : PBO)

Treatment:

Drug: MAM01 150 mg IM

Drug: Placebo IM

Part B: Cohort 4c (Healthy Infants): 150 mg MAM01 or placebo IV

Experimental group

Description:

Participants will be randomized in 3:1 ratio (MAM01: PBO)

Treatment:

Drug: Placebo IV

Drug: MAM01 150 mg IV