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Completed

NCT Number: NCT05891236

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

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.

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Key information

Conditions

Malaria Infections Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

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

Baltimore, Maryland, 21201, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

MAM01 1.5 mg/kg

Biological

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

Placebo

Biological

Placebo will be administered via IV route.

MAM01 5 mg/kg

Biological

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

MAM01 10 mg/kg

Biological

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

MAM01 40 mg/kg

Biological

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

MAM01 450 mg

Biological

MAM01 will be administered via SC route.

Control

Other

No drug or placebo will be administered.

MAM01 600 mg

Biological

MAM01 will be administered via SC route.

MAM01 900 mg

Biological

MAM01 will be administered via SC route.

Primary outcomes

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

    Time frame: Day 1 to Day 7 post dose

    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.

  2. Number of Participants Reporting Unsolicited Adverse Events

    Time frame: Through Day 28 post dose

    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.

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

    Time frame: Up to Day 168

    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.

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

    Time frame: Through Day 336

    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.

  5. Number of Participants With Clinically Significant Changes in Serum Chemistry Parameters

    Time frame: Through Day 336

    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.

  6. Number of Participants With Clinically Significant Changes in Hematology Parameters

    Time frame: Through Day 336

    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.

Secondary outcomes

  1. Maximal Observed Concentration (Cmax) Following Single Dose of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  2. Cmax Following Repeat Dosing of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  3. Area Under the Curve (AUC) From Time=0 to the Last Measurable Concentration (AUC0-t) Following Single Dose of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  4. AUC (0-t) Following Repeat Dosing of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  5. Partial AUC's Time= 0 to the CHMI Challenge (AUC0-CHMI) of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  6. Concentration at the Time of CHMI (CCHMI) of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  7. Blood Terminal Elimination Rate Constant (λz) of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  8. Terminal Half Life (t1/2) Following Single Dose of MAM01

    Time frame: 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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  9. t1/2 Following Repeat Dosing of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  10. AUC From Time=0 Extrapolated to Infinity (AUC0-infinity) of MAM01

    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

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  11. Absolute Bioavailability of SC Formulation Following Repeated Dosing of MAM01

    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, 280 and 378 post-dose

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.

  12. Accumulation Ratio (AUC0-168) Following Repeated Doses of MAM01

    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 and 168 post-dose

    Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics. The accumulation ratio was calculated as the ratio of AUC (0-168) (post first dose) to AUC (210-378) (post redose).

  13. Number of Participants With Confirmed Pf Infection Assessed by Quantitative Polymerase Chain Reaction Assay (qRT-PCR) After CHMI

    Time frame: Up to Day 27 post-CHMI

    The characterization of protective efficacy against Pf following CHMI challenge, was assessed by evaluating the presence or absence of Pf infection as determined by qRT-PCR after CHMI (planned through 4 weeks post-CHMI) and evaluating the time to parasitemia after CHMI in each cohort.

  14. Time to Parasitemia After CHMI

    Time frame: Up to Day 27 post-CHMI

    Parasitemia was assessed by qRT-PCR up to Day 27 following CHMI. In addition, a thick blood smear was prepared for microscopic analysis, which was examined only once the first qRT-PCR sample tested positive. Daily parasitemia monitoring continued until the participant had a confirmed initial positive qRT-PCR. The first positive qRT-PCR triggered either a second PCR test or microscopic analysis of the blood smear. Once two positive results were obtained, rescue therapy was initiated.

  15. Cohorts 1, 4 and 5: Numbers of Participants With Seroconversion

    Time frame: Up to Day 280

    The formation of ADAs (immunogenicity) following MAM01 SC and/or IV administration) was evaluated by measuring titers of ADA to MAM01 to last study visit for all participants. Capillary blood samples and selected serum samples were collected on volumetric absorptive micro-sampling (VAMS) devices at timepoints.

  16. Cohorts 2 and 3: Numbers of Participants Receiving 2 Doses With Seroconversion

    Time frame: Up to Day 378

    The formation of ADAs (immunogenicity) following MAM01 SC and/or IV administration) was evaluated by measuring titers of ADA to MAM01 to last study visit for all participants. Capillary blood samples and selected serum samples were collected on volumetric absorptive micro-sampling (VAMS) devices at timepoints.

  17. Cohort 6: Numbers of Participants With Seroconversion

    Time frame: Up to Day 84

    The formation of ADAs (immunogenicity) following MAM01 SC and/or IV administration) was evaluated by measuring titers of ADA to MAM01 to last study visit for all participants. Capillary blood samples and selected serum samples were collected on volumetric absorptive micro-sampling (VAMS) devices at timepoints.

Sponsors and collaborators

Lead sponsor

Gates Medical Research Institute

Other

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 6, 2023
Registry last updated
Jun 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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