MalariaPhase 1NCT05891236
Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults
A Phase 1 study testing MAM01 1.5 mg/kg, MAM01 5 mg/kg and MAM01 10 mg/kg in people with Malaria, run by Gates Medical Research Institute at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- MAM01 1.5 mg/kg, MAM01 5 mg/kg and MAM01 10 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Aug 2023to 13 Dec 2024
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Vaccine Development and Global Health, 685 W. Baltimore Street
Baltimore, Maryland, 21201
About this study
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
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.
- Conditions
- Malaria
- Being tested
- MAM01 1.5 mg/kg, Placebo, MAM01 5 mg/kg, MAM01 10 mg/kg, MAM01 40 mg/kg
- 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
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAM01 1.5 mg/kgBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Single Ascending Dose (SAD): Dose escalation cohort 1: MAM01 and placebo Intravenous (IV) | Experimental | 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. Receives: Biological: MAM01 1.5 mg/kg; Biological: Placebo |
| Part A: SAD dosing: Dose escalation Cohort 2: MAM01 and placebo SC | Experimental | 7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg SC or placebo Receives: Biological: MAM01 5 mg/kg; Biological: Placebo |
| Part A: SAD dosing: Dose escalation Cohort 3: MAM01 and placebo IV | Experimental | 7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 5 mg/kg IV or placebo. Receives: Biological: Placebo; Biological: MAM01 5 mg/kg |
| Part A: SAD dosing: Dose escalation Cohort 4: MAM01 and placebo IV | Experimental | 8 participants will be randomly assigned in a 6:2 ratio to receive MAM01 10 mg/kg IV or placebo. Receives: Biological: Placebo; Biological: MAM01 10 mg/kg |
| Part A: SAD dosing: Dose escalation Cohort 5: MAM01 and placebo IV | Experimental | 7 participants will be randomly assigned in a 6:1 ratio to receive MAM01 40 mg/kg IV or placebo Receives: Biological: Placebo; Biological: MAM01 40 mg/kg |
| Part A: Multiple Ascending Dose (MAD) (Repeat dosing): MAM01 | Experimental | Participants from Cohort 2 and from Cohort 3 will receive 5 mg/kg MAM01 SC. Receives: Biological: MAM01 5 mg/kg |
| Part B: Dose Expansion Cohort 6: Group 1: MAM01 | Experimental | 6 participants will receive a 450 mg SC dose of MAM01. The dose was selected by applying a PK-pharmacodynamic (PD) model from the Part A data to estimate a (data-driven) protection threshold at Controlled Human Malaria Infection (CHMI). Receives: Biological: MAM01 450 mg |
| Part B: Dose Expansion Cohort 6: Group 2: MAM01 | Experimental | 8 participants will receive a 600 mg SC dose of MAM01. The dose was selected by applying a PK-PD model from the Part A data to estimate a (data-driven) protection threshold at CHMI Receives: Biological: MAM01 600 mg |
| Part B: Dose Expansion Cohort 6: Group 3: MAM01 | Experimental | 8 participants will receive 900 mg SC dose of MAM01. The dose was selected by applying a PK-PD model from the Part A data to estimate a (data-driven) protection threshold at CHMI. Receives: Biological: MAM01 900 mg |
| Internal Infectivity Controls | Experimental | 6 participants will be enrolled into a non-randomized group prior to CHMI. These participants will receive no treatment and act as infectivity controls Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through Day 336
Secondary outcomes (17)
Maximal Observed Concentration (Cmax) Following Single Dose of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Cmax Following Repeat Dosing of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Area Under the Curve (AUC) From Time=0 to the Last Measurable Concentration (AUC0-t) Following Single Dose of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
AUC (0-t) Following Repeat Dosing of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Partial AUC's Time= 0 to the CHMI Challenge (AUC0-CHMI) of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Concentration at the Time of CHMI (CCHMI) of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Blood Terminal Elimination Rate Constant (λz) of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Terminal Half Life (t1/2) Following Single Dose of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
t1/2 Following Repeat Dosing of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
AUC From Time=0 Extrapolated to Infinity (AUC0-infinity) of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Absolute Bioavailability of SC Formulation Following Repeated Dosing of MAM01
Serum from venous blood samples was collected for measurement of MAM01 pharmacokinetics.
Measured: 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
Accumulation Ratio (AUC0-168) Following Repeated Doses of MAM01
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).
Measured: 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
Number of Participants With Confirmed Pf Infection Assessed by Quantitative Polymerase Chain Reaction Assay (qRT-PCR) After 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.
Measured: Up to Day 27 post-CHMI
Time to Parasitemia After 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.
Measured: Up to Day 27 post-CHMI
Cohorts 1, 4 and 5: Numbers of Participants With Seroconversion
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.
Measured: Up to Day 280
Cohorts 2 and 3: Numbers of Participants Receiving 2 Doses With Seroconversion
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.
Measured: Up to Day 378
Cohort 6: Numbers of Participants With Seroconversion
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.
Measured: Up to Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2023
- Study start14 Aug 2023
- Primary completion13 Dec 2024
- Study completion13 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gates Medical Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- +1 866 789 5767, Study director, Gates Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05891236
- Sponsor's protocol ID
- Gates MRI-MAM01-101
- Status last verified
- May 2026
- First submitted
- 26 May 2023
- Last updated
- 12 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lyke KE, Berry AA, Laurens MB, Winkler J, Joshi S, Koudjra AR, Butler L, Billingsley PF, Pascini T, Patil A, Sim BKL, Fitzgerald G, Riegel J, Andrews K, Levi M, Anderson AB, Wells CD, Liu H, Huleatt J, Miller RS. Human monoclonal antibody MAM01 for protection against malaria in adults in the USA: a first-in-human, phase 1, dose-escalation, double-blind, placebo-controlled, adaptive trial. Lancet Infect Dis. 2026 Feb;26(2):170-181. doi: 10.1016/S1473-3099(25)00481-5. Epub 2025 Sep 23.
PubMed 41005346