Clinical trial NCT05891236: Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Keywords: Healthy volunteers
MAM01 monoclonal antibody
First-in-Human
Dose-escalation
Single ascending dose
Multiple ascending dose
Recruiting
Malaria vaccine
Mosquito
Gates
Prevention
Phase 1
Nonprofit
Lead sponsor: Bill & Melinda Gates Medical Research Institute
Sponsor class: OTHER
First posted: 2023-06-06
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants reporting solicited local and systemic adverse events (AEs) in the SC cohorts
timeFrame: Through 7 days post-dose
measure: Number of participants reporting unsolicited AEs (single dose or multiple dose)
timeFrame: Through Day 28
measure: Number of participants reporting serious adverse events (SAEs) including suspected unexpected serious adverse reactions (SUSARs) and adverse events special interest (AESIs)
timeFrame: Through 168 days post-dose
measure: Number of re-dosed participants reporting SUSARs, SAEs and AESIs
timeFrame: Through 378 days
measure: Number of participants with safety laboratory assessments by grade (grade 1 and above)
timeFrame: Up to 378 Days
Secondary outcomes:
measure: Maximal observed concentration (Cmax) following single and repeat dosing of MAM01
timeFrame: 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
measure: Area under the curve (AUC) from Time=0 to the last measurable concentration (AUC0-t) of MAM01
timeFrame: 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
measure: Partial AUC's Time= 0 to the CHMI challenge (AUC0-CHMI) of MAM01
timeFrame: 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
measure: Concentration at the time of CHMI (CCHMI) following single and repeat dosing of MAM01
timeFrame: 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
measure: Blood terminal elimination rate constant (λz) following single and repeat dosing of MAM01
timeFrame: 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
measure: Terminal half life (t1/2) of MAM01
timeFrame: 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
measure: AUC from Time=0 extrapolated to infinity (AUC0-infinity) of MAM01
timeFrame: 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
measure: Percentage (%) AUC extrapolated (% AUCext) of MAM01
timeFrame: 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
measure: Bioavailability of SC formulation following single and repeat dosing of MAM01
timeFrame: 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
measure: Part A: Cohorts 2 and 3: Accumulation ratio (AUC0-168) of MAM01
timeFrame: 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
measure: Part A: Cohorts 2 and 3: AUC (210-378) of MAM01
timeFrame: Day 210 and up to Day 378
measure: Part A: Cohorts 2 and 3: Accumulation ratio AUC (210-378) of MAM01
timeFrame: Day 210 and up to Day 378
measure: Number of participants with presence or absence of Pf infection assessed by quantitative polymerase chain reaction assay (qRT-PCR) after CHMI
timeFrame: Through Day 27 post CHMI
measure: Time to parasitemia after CHMI in Efficacy Population
timeFrame: Up to Day 378
measure: Part A: Cohorts 1, 4 and 5: Titers of anti-drug antibodies (ADAs) following administration of MAM01 in Immunogenicity Population
timeFrame: Up to Day 280
measure: Part A: Cohorts 2 and 3: Titers of ADAs following administration of MAM01 in Immunogenicity Population
timeFrame: Up to Day 378
measure: Part B: Cohort 6: Titers of Number of participants with ADAs following administration of MAM01 in Immunogenicity Population
timeFrame: Up to Day 84
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Center for Vaccine Development and Global Health, 685 W. Baltimore Street
state: Maryland
Study officials:
affiliation: Bill & Melinda Gates Medical Research Institute
name: +1 866 789 5767
role: STUDY_DIRECTOR
References: