Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults

Gates Medical Research Institute63 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

Malaria

Interventions

MAM01 1.5 mg/kg

1.5 mg/kg MAM01 will be administered via IV route.

PlaceboBIOLOGICAL

Placebo will be administered via IV route.

MAM01 5 mg/kgBIOLOGICAL

5 mg/kg MAM01 will be administered via SC route.

MAM01 10 mg/kgBIOLOGICAL

10 mg/kg MAM01 will be administered via IV route.

MAM01 40 mg/kgBIOLOGICAL

40 mg/kg MAM01 will be administered via IV route.

MAM01 450 mgBIOLOGICAL

MAM01 will be administered via SC route.

PlaceboBIOLOGICAL

Placebo will be administered via SC route.

MAM01 5 mg/kgBIOLOGICAL

5 mg/kg MAM01 will be administered via IV route.

ControlOTHER

No drug or placebo will be administered.

MAM01 600 mgBIOLOGICAL

MAM01 will be administered via SC route.

MAM01 900 mgBIOLOGICAL

MAM01 will be administered via SC route.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Center for Vaccine Development and Global Health, 685 W. Baltimore Street

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Number of Participants Reporting Solicited Adverse Events (AEs) in the Subcutaneous Cohorts

Solicited AEs were defined events participants were specifically asked about, which were recorded by participants in the memory aid card. Solicited AES included local injection site AEs (pain, redness, swelling, itching and bruising) and systemic AEs (fever, chills, headache, fatigue, nausea, muscle pain and joint pain). A Solicited AE does not necessarily have a causal relationship with the intervention.

Time frame: Day 1 to Day 7 post dose

Number of Participants Reporting Unsolicited Adverse Events

In this study an unsolicited AE is any AE not captured as a solicited AE in the Memory Aid Card between Day 0 and Day 7 after MAM01 dosing, and all AEs occurring after Day 7 post dose were collected as Unsolicited AEs.

Time frame: Through Day 28 post dose

Number of Participants Reporting Serious Adverse Events (SAEs) Including Suspected Unexpected Serious Adverse Reactions (SUSARs) and Adverse Events Special Interest (AESIs)

A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is a medically significant / important event or reaction. SUSARs are AEs reported for a clinical trial participant, which is assessed by the Sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug. AESIs are adverse events that the Sponsor wants to monitor closely and which require expedited reporting.

Time frame: Up to Day 168

Number of Participants Who Received 2 Doses Reporting SUSARs, SAEs and AESIs

A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is a medically significant / important event or reaction. SUSARs are AEs reported for a clinical trial participant, which is assessed by the Sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug. AESIs are adverse events that the Sponsor wants to monitor closely and which require expedited reporting.

Time frame: Through Day 336

Number of Participants With Clinically Significant Changes in Serum Chemistry Parameters

Blood samples were collected for the assessment of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total carbon-dioxide (CO2), chloride, total bilirubin, creatinine, blood urea nitrogen, glucose, albumin, total protein, sodium and potassium.

Time frame: Through Day 336

Number of Participants With Clinically Significant Changes in Hematology Parameters

Blood samples were collected for the assessment of complete blood count (CBC) including hemoglobin, platelet count, and white blood cell counts, and differential to include the absolute counts for neutrophils, lymphocytes, eosinophils, and monocytes.

Time frame: Through Day 336