Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults
Malaria
About this trial
This is an interventional treatment trial for Malaria focused on measuring Healthy volunteers, MAM01 monoclonal antibody, First-in-Human, Dose-escalation, Single ascending dose, Multiple ascending dose
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 completion of the trial visits. Capable of giving signed Informed Consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this 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 1. Anticipated use of medications known to cause drug reactions with chloroquine or atovaquoneproguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Center for Vaccine Development and Global Health, 685 W. Baltimore StreetRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Part A: Single Ascending Dose (SAD): Dose escalation cohort 1: MAM01 and placebo Intravenous (IV)
Part A: SAD dosing: Dose escalation Cohort 2: MAM01 and placebo SC
Part A: SAD dosing: Dose escalation Cohort 3: MAM01 and placebo IV
Part A: SAD dosing: Dose escalation Cohort 4: MAM01 and placebo IV
Part A: SAD dosing: Dose escalation Cohort 5: MAM01 and placebo IV
Part A: Multiple Ascending Dose (MAD) (Repeat dosing): MAM01 and placebo SC
Part B: Dose Expansion Cohort 6: Group 1: MAM01 and placebo SC (optional)
Part B: Dose Expansion Cohort 6: Group 2: MAM01 and placebo SC (optional)
Part B: Dose Expansion Cohort 6: Group 3: MAM01 and placebo SC (optional)
2 sentinel participants will be randomized in a 1:1 ratio to receive MAM01 1.5 milligrams per kilogram (mg/kg) IV or placebo. Following at least a 24-hour safety review period, the 6 remaining participants of Cohort 1 will be randomized in a 5:1 ratio to receive MAM01 1.5 mg/kg IV or placebo.
7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg SC or placebo
7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg IV or placebo.
8 participants will be randomly assigned in a 6:2 ratio to receive MAM01 10 mg/kg IV or placebo.
7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 40 mg/kg IV or placebo
Participants from Cohort 2 and from Cohort 3 will receive 5 mg/kg MAM01 SC.
8 participants will receive a single SC dose of either MAM01 or placebo. The dose will be selected by applying a PK-pharmacodynamic (PD) model from the Part A data to estimate a (data-driven) protection threshold.
8 participants will receive a single SC dose of either MAM01 or placebo. The dose will be selected by applying a PK-PD model from the Part A data to estimate a (data-driven) protection threshold.
8 participants will receive a single SC dose of either MAM01 or placebo. The dose will be selected by applying a PK-PD model from the Part A data to estimate a (data-driven) protection threshold.