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

Primary Purpose

Malaria

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MAM01
Placebo
Sponsored by
Bill & Melinda Gates Medical Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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)

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of participants reporting solicited local and systemic adverse events (AEs) in the SC cohorts
Number of participants reporting unsolicited AEs (single dose or multiple dose)
Number of participants reporting serious adverse events (SAEs) including suspected unexpected serious adverse reactions (SUSARs) and Adverse Events Special Interest (AESIs)
Number of re-dosed participants reporting SUSARs, SAEs and AESIs
Number of participants with safety laboratory assessments by grade (grade 1 and above)

Secondary Outcome Measures

Maximal observed blood concentration (Cmax) following single and repeat dosing of MAM01
Area under the curve (AUC) from Time=0 to the last measurable concentration (AUC0-t) following single and repeat dosing of MAM01
Partial AUC's Time= 0 to the CHMI challenge (AUC0-CHMI) following single and repeat dosing of MAM01
Concentration at the time of CHMI (CCHMI) following single and repeat dosing of MAM01
Blood terminal elimination rate constant (λz) following single and repeat dosing of MAM01
Terminal half life (t1/2) following single and repeat dosing of MAM01
AUC from Time=0 extrapolated to infinity (AUC0-infinity) following single and repeat dosing of MAM01
Percentage (%) AUC extrapolated (% AUCext) following single and repeat dosing of MAM01
Bioavailability of SC formulation following single and repeat dosing of MAM01
Part A: Cohorts 2 and 3: Accumulation ratio (AUC0-168) following single and repeat dosing of MAM01
Part A: Cohorts 2 and 3: AUC (169-336) following single and repeat dosing of MAM01
Number of participants with presence or absence of Pf infection assessed by quantitative polymerase chain reaction assay (qRT-PCR)) after CHMI
Time to parasitemia after CHMI
Part A: Cohorts 1, 4 and 5: Number of participants with anti-drug antibodies (ADAs) following administration of MAM01
Part A: Cohorts 2 and 3: Number of participants with ADAs following administration of MAM01
Part B: Number of participants with ADAs following administration of MAM01

Full Information

First Posted
May 26, 2023
Last Updated
August 23, 2023
Sponsor
Bill & Melinda Gates Medical Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05891236
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 14, 2023 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bill & Melinda Gates Medical Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a First-in-Human (FiH) double-blind, randomized, placebo-controlled, 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Healthy volunteers, MAM01 monoclonal antibody, First-in-Human, Dose-escalation, Single ascending dose, Multiple ascending dose

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
61 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A: Single Ascending Dose (SAD): Dose escalation cohort 1: MAM01 and placebo Intravenous (IV)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A: SAD dosing: Dose escalation Cohort 2: MAM01 and placebo SC
Arm Type
Experimental
Arm Description
7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg SC or placebo
Arm Title
Part A: SAD dosing: Dose escalation Cohort 3: MAM01 and placebo IV
Arm Type
Experimental
Arm Description
7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg IV or placebo.
Arm Title
Part A: SAD dosing: Dose escalation Cohort 4: MAM01 and placebo IV
Arm Type
Experimental
Arm Description
8 participants will be randomly assigned in a 6:2 ratio to receive MAM01 10 mg/kg IV or placebo.
Arm Title
Part A: SAD dosing: Dose escalation Cohort 5: MAM01 and placebo IV
Arm Type
Experimental
Arm Description
7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 40 mg/kg IV or placebo
Arm Title
Part A: Multiple Ascending Dose (MAD) (Repeat dosing): MAM01 and placebo SC
Arm Type
Experimental
Arm Description
Participants from Cohort 2 and from Cohort 3 will receive 5 mg/kg MAM01 SC.
Arm Title
Part B: Dose Expansion Cohort 6: Group 1: MAM01 and placebo SC (optional)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part B: Dose Expansion Cohort 6: Group 2: MAM01 and placebo SC (optional)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part B: Dose Expansion Cohort 6: Group 3: MAM01 and placebo SC (optional)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
MAM01
Intervention Description
MAM01 will be administered via IV or SC route
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered via IV or SC route.
Primary Outcome Measure Information:
Title
Number of participants reporting solicited local and systemic adverse events (AEs) in the SC cohorts
Time Frame
Through 7 days post-dose
Title
Number of participants reporting unsolicited AEs (single dose or multiple dose)
Time Frame
Through Day 28
Title
Number of participants reporting serious adverse events (SAEs) including suspected unexpected serious adverse reactions (SUSARs) and Adverse Events Special Interest (AESIs)
Time Frame
Through 168 days post-dose
Title
Number of re-dosed participants reporting SUSARs, SAEs and AESIs
Time Frame
Through 336 days
Title
Number of participants with safety laboratory assessments by grade (grade 1 and above)
Time Frame
Up to 336 Days
Secondary Outcome Measure Information:
Title
Maximal observed blood concentration (Cmax) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Area under the curve (AUC) from Time=0 to the last measurable concentration (AUC0-t) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Partial AUC's Time= 0 to the CHMI challenge (AUC0-CHMI) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Concentration at the time of CHMI (CCHMI) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Blood terminal elimination rate constant (λz) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Terminal half life (t1/2) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
AUC from Time=0 extrapolated to infinity (AUC0-infinity) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Percentage (%) AUC extrapolated (% AUCext) following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Bioavailability of SC formulation following single and repeat dosing of MAM01
Time Frame
Pre-dose, Day 28 and Day 84 post-dose
Title
Part A: Cohorts 2 and 3: Accumulation ratio (AUC0-168) following single and repeat dosing of MAM01
Time Frame
Pre-dose and up to Day 168
Title
Part A: Cohorts 2 and 3: AUC (169-336) following single and repeat dosing of MAM01
Time Frame
Day 169 and up to Day 336
Title
Number of participants with presence or absence of Pf infection assessed by quantitative polymerase chain reaction assay (qRT-PCR)) after CHMI
Time Frame
Through Day 27 post CHMI
Title
Time to parasitemia after CHMI
Time Frame
Up to Day 336
Title
Part A: Cohorts 1, 4 and 5: Number of participants with anti-drug antibodies (ADAs) following administration of MAM01
Time Frame
Up to Day 280
Title
Part A: Cohorts 2 and 3: Number of participants with ADAs following administration of MAM01
Time Frame
Up to Day 336
Title
Part B: Number of participants with ADAs following administration of MAM01
Time Frame
Up to Day 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gates MRI
Phone
+1 857 702 2108
Email
clinical.trials@gatesmri.org
First Name & Middle Initial & Last Name or Official Title & Degree
Gates MRI (Toll Free Number)
Phone
+1 866 789 5767
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
+1 866 789 5767
Organizational Affiliation
Bill & Melinda Gates Medical Research Institute
Official's Role
Study Director
Facility Information:
Facility Name
Center for Vaccine Development and Global Health, 685 W. Baltimore Street
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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