Clinical trial NCT06408857: Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Malaria
Plasmodium falciparum
MAM01
De-Escalation
Dose Escalation
Perennial Malaria Transmission
Antibody
Monoclonal
Prevention
Pediatric
Lead sponsor: Bill & Melinda Gates Medical Research Institute
Sponsor class: OTHER
First posted: 2024-05-10
Enrollment: 139
Sex: ALL
Minimum age (years): 3
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants reporting Treatment-emergent adverse events (TEAEs)
timeFrame: Up to 28 days post dose (Part A and B)
measure: Number of participants reporting serious adverse events (SAEs), adverse events of special interest (AESI), and AEs leading to discontinuation
timeFrame: Up to 182 days post dose
measure: Number of participants reporting solicited systemic AEs and solicited injection site AEs (applicable to IM dosing)
timeFrame: Up to 7 days post dose
measure: Number of participants reporting solicited systemic AEs and solicited injection site AEs (applicable to SC dosing)
timeFrame: Up to 7 days post dose
Secondary outcomes:
measure: Percentage of participants with graded abnormal clinical hematology and chemistry laboratory results
timeFrame: Up to 28 days post dose
measure: Maximal observed blood concentration of MAM01 following the first dose (Cmax1)
timeFrame: Pre- and post-dose (IV dosing groups only) at Day 1, 4, 7, 14, 28, 56, 84, 112, 140, and 182
measure: Concentration at Day 182 (C182)
timeFrame: At Day 182 post first dose
measure: Total Area Under the Concentration Curve (AUC) Day 0 - Day 182
timeFrame: From 0 to 182 days post dose
measure: Percentage of participants with antidrug antibodies (ADAs) to MAM01
timeFrame: At Days 1, 28, 84, and 182
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: JCRC-Joint Clinical Research Centre
city: Tororo
country: Uganda
facility: IDRC-Infectious Disease Research Collaboration, IDRC Tororo Hospital Station Road
Study officials:
References: