Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population

Healthy Volunteers Clinical Trial

Official title:

A Phase 1b, Age De-Escalation/Dose Escalation Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of MAM01 in Adults, Children, and Special Pediatric Populations in a Setting of Perennial Malaria Transmission in Africa

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06408857
• Other study ID #: Gates MRI-MAM01-103
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 2024
• Est. completion date: May 2026

Study information

• Verified date: May 2024
• Source: Bill & Melinda Gates Medical Research Institute
• Contact: Gates MRI
• Phone: +1 866 789 5767
• Email: clinical.trials[@]gatesmri.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will test a new drug (MAM01) to find which doses are safe and could help prevent people from getting malaria. The study will take place in parts of Africa where malaria is common. Parts A and B of the study will first test single doses of MAM01 in healthy adults, then after safety review, in older children, and then after additional safety review, in infants. Part C will then test single doses of MAM01 in children and infants who have a medical problem that could put them at greater risk if they get malaria.

Description:

This is a Phase 1b, age de-escalation/dose escalation trial that will be conducted in a setting of perennial high Plasmodium falciparum (malaria parasite) transmission in Africa. The study will be conducted in 3 parts: Part A (Age De-escalation/Dose Escalation in Adults and Older Children); Part B (Age De-escalation/Dose Escalation in Younger Children) and Part C (Special Pediatric Populations).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 264
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Months to 55 Years

Eligibility

Inclusion Criteria:

PART A

• Age Cohort 1: male or female adults aged 18 to 55 years inclusive at the time of signing the informed consent form (ICF), who are capable of, and willing to provide, informed consent

• Age Cohort 2: male or female children aged 5 to 10 years inclusive at the time their parent or Legally Acceptable Representative (LAR) signs the ICF, and they sign the assent form

• Healthy, as determined by Investigator assessment, including medical history, physical examination, and screening laboratory results

• All dosing groups: hemoglobin level = 8 grams per deciliter (g/dL)

• All dosing groups: living within local jurisdiction of trial site(s) and available for the duration of the trial for all cohorts

• Age Cohort 1: female participants of childbearing potential must be nonpregnant and agree to avoid becoming pregnant by using an acceptable contraception method

• Age Cohort 2: height and weight Z-scores =-2

• Age Cohort 2: female participants must be pre-menarche

PART B

• Age Cohort 3: male or female children aged 12 months to <5 years at the time their parent or LAR signs the ICF

• Age Cohort 4: male or female infant children aged 3 to <12 months and weighing at least 5 kilograms (kg) at the time their parent or LAR signs the ICF

• Healthy, as determined by Investigator assessment, including medical history, physical examination, and screening laboratory results

• All dosing groups: hemoglobin level = 8g/dL

• All dosing groups: height and weight Z-scores =-2

• All dosing groups: living within local jurisdiction of trial site(s) and available for the duration of the trial

PART C - All Participants

• Male or female children aged 3 months to <5 years at the time their parent or LAR signs the ICF

• All dosing groups: living within local jurisdiction of trial site(s) and available for the duration of the trial

Dosing Group 5a -Severe Anemia

• Current or recent (< 14 days prior) hospitalization for severe anemia (hemoglobin < 5 g/dL)

• Blood transfusions (if required) completed prior to investigational product (IP) administration

• Completed, undergoing, or prescribed a course of oral antimalarial treatment as part of anemia management

Dosing Group 5b -Severe Acute Malnutrition

• Diagnosis of severe acute malnutrition based on:

1. Weight-for-height z-score <-3; or

2. Mid-upper-arm circumference measurements (<11.5 centimeters [cm] for children aged >6 months and <11 cm for infants aged 3-5 months); or

3. Presence of kwashiorkor (edematous malnutrition).

• Had completed the stabilization phase of treatment in the hospital for severe acute malnutrition or direct enrollment in an outpatient therapeutic care (OTC) program

Dosing Group 5c -Human immunodeficiency virus (HIV) Infection

• HIV positive by serology or HIV rapid test or history of positive viral load for HIV

• HIV treated by antiretroviral therapy for at least 3 months

Dosing Group 5d -Sickle Cell Disease

• Sickle cell disease, including hemoglobin SS, hemoglobin SC, and sickle-beta thalassemia confirmed by hemoglobin electrophoresis at Screening

• On stable disease-modifying regimen (eg, hydroxyurea) for at least 4 weeks

Exclusion Criteria:

PART A & PART B

• Within 48 hours prior to randomization, acute febrile illness

• Sickle cell disease or history of splenectomy

• Use of antimalarial chemoprevention or treatment, and/or antibiotics with known antimalarial effects (eg, clotrimoxazole, azithromycin, tetracyclines) within 30 days prior to dosing

• Enrolled in another clinical trial within 90 days prior to Screening or planning to participate in another trial during, or within 1 year following, their participation in this trial

• Received any doses of a malaria vaccine or other monoclonal antibodies (mAb) to Pf

• Eligible to receive a malaria vaccine (RTS, S/AS01 or R21/Matrix-M) in their catchment area when it is available

• History of allergy or hypersensitivity or contraindications to trial drugs (including those used as empirically treatment for Pf to clear any existing parasitemia), excipients or related substances

• Any history of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the trial

• History of any autoimmune disease or immunodeficiency or other impairment to the immune system, including HIV infection

• Use of chronic (= 14 days) immunosuppressive agents including systemic steroids (eg, prednisone >10 milligrams per day [mg/day]) within 30 days prior to dosing. Use of inhaled or topical corticosteroids is permitted

• Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising with blood draws

• Receipt of immunoglobulins and/or blood products within the past 6 months

• Any current uncontrolled medical or psychiatric condition, or substance abuse problems that in the opinion of the Investigator, will make it unlikely for participant to comply with the protocol, may interfere with study assessments, or could jeopardize the safety of the participant

• Any contraindication for a subcutaneous injection, intravenous injection, or intramuscular injection, as applicable

• For Part A (Age Cohort 1) female participants who are breastfeeding, pregnant, or unable or unwilling to adhere to required contraception

• For Part A (Age Cohort 2) and Part B, in the opinion of the Investigator, the parent or LAR may not be able to ensure participant compliance with the requirements of the trial

PART C - All Participants

• Within 48 hours prior to randomization, acute febrile illness

• Enrolled in another clinical trial within 90 days prior to Screening or planning to participate in another trial during, or within 1 year following, their participation in this trial

• Received any doses of a malaria vaccine or other mAb to Pf

• Eligible to receive a malaria vaccine (RTS,S/AS01 or R21/Matrix-M) in their catchment area when it is available

• History of allergy or hypersensitivity or contraindications to trial drugs (including those used as empirically treatment for Pf to clear any existing parasitemia), excipients or related substances

• Any history of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the trial

• Use of chronic (= 14 days) immunosuppressive agents including systemic steroids (eg, prednisone >10 mg/day) within 30 days prior to dosing. Use of inhaled or topical corticosteroids is permitted

• Serious comorbidity likely to be associated with mortality unrelated to infection such as severe heart disease or malignancy

• Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising with blood draws

• Any current uncontrolled medical or psychiatric condition that in the opinion of the Investigator, will make it unlikely for participant or their parent or LAR to comply with the protocol, or may interfere with study assessments, or could jeopardize the safety of the participant

• In the opinion of the Investigator, the parent or LAR may not be able to ensure participant compliance with the requirements of the trial

Dosing Group 5a - Severe Anemia

• Anemia caused by trauma or malignancy

• Known sickle cell disease or hemoglobin SS, hemoglobin SC or sickle-beta thalassemia by hemoglobin electrophoresis at Screening

• HIV infection

• History of any autoimmune disease or immunodeficiency or other impairment to the immune system

• Severe acute malnutrition

• Any contraindication for an intravenous injection

Dosing Group 5b - Severe Acute Malnutrition

• Known sickle cell disease or hemoglobin SS, hemoglobin SC or sickle-beta thalassemia by hemoglobin electrophoresis at Screening

• HIV infection

• History of any autoimmune disease or immunodeficiency or other impairment to the immune system

• Severe anemia (Hemoglobin <5 g/dL or clinical indication for blood transfusion)

• Any contraindication for an intramuscular injection

Dosing Group 5c -HIV Infection

• Acute anti-retroviral syndrome

• CD4 count < 200 cells per cubic milliliters (cells/mm3)

• Active opportunistic infection

• Hemoglobin < 8g/dL

• Known sickle cell disease or hemoglobin SS, hemoglobin SC, sickle-beta thalassemia by hemoglobin electrophoresis at Screening

• Severe acute malnutrition

• Any contraindication for a subcutaneous injection

Dosing Group 5d -Sickle Cell Disease

• Acute sickle crisis in previous 2 weeks

• Hemoglobin <5 g/dL or clinical indication for blood transfusion

• HIV infection

• History of any autoimmune disease or immunodeficiency or other impairment to the immune system

• Severe acute malnutrition

• Any contraindication for a subcutaneous injection

Related Conditions & MeSH terms

• Healthy Volunteers
• Malaria

Intervention

Drug:
• MAM01 300 mg SC
MAM01 300 mg will be administered SC
• MAM01 300 mg IM
MAM01 300 mg will be administered IM route
• MAM01 600 mg SC
MAM01 600 mg will be administered SC
• MAM01 2000 mg IM
MAM01 2000 mg will be administered IM
• MAM01 150 mg SC
MAM01 150 mg will be administered SC
• MAM01 75 mg SC
MAM01 75 mg will be administered SC
• MAM01 225 mg SC
MAM01 225 mg will be administered SC
• MAM01 150 mg IM
MAM01 150 mg will be administered IM
• MAM01 150 mg IV
MAM01 150 mg will be administered IV
• Placebo IV
Placebo will be administered IV
• MAM01 150 mg
MAM01 150 mg route of administration (SC, IM, or IV) will be selected at Investigator's discretion
• Placebo IM
Placebo will be administered IM
• Placebo SC
Placebo will be administered SC

Locations

Country	Name	City	State
Kenya	KEMRI CGRH, Kenya	Kisumu
Uganda	IDRC-Infectious Disease Research Collaboration, IDRC Masafu General Hospital Manjanji Road	Busia
Uganda	JCRC-Joint Clinical Research Centre	Kampala
Uganda	IDRC-Infectious Disease Research Collaboration, IDRC Tororo Hospital Station Road	Tororo

Sponsors (1)

Lead Sponsor	Collaborator
Bill & Melinda Gates Medical Research Institute

Countries where clinical trial is conducted

Kenya,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants reporting Treatment-emergent adverse events (TEAEs)		Up to 28 days post dose
Primary	Number of participants reporting serious adverse events (SAEs), adverse events of special interest (AESI), and AEs leading to discontinuation		Up to 182 days post dose (Parts A and C) or 364 days post dose (Part B)]
Primary	Number of participants reporting solicited systemic AEs and solicited injection site AEs (applicable to IM dosing)		Up to 7 days post dose
Primary	Number of participants reporting solicited systemic AEs and solicited injection site AEs (applicable to SC dosing)		Up to 7 days post dose
Secondary	Percentage of participants with graded abnormal clinical hematology and chemistry laboratory results		Up to 28 days post dose
Secondary	Maximal observed blood concentration of MAM01 following the first dose (Cmax1)	Capillary blood samples will be collected for the analysis pharmacokinetic parameters. Blood concentrations of MAM01 will be measured using a validated immunoassay.	Pre- and post-dose (IV dosing groups only) at Day 1, 4, 7, 14, 28, 56, 84, 112, 140, and 182
Secondary	Concentration at Day 182 (C182)		At Day 182 post first dose
Secondary	Total Area Under the Concentration Curve (AUC) Day 0 - Day 182		From 0 to 182 days post first dose
Secondary	Cmax following the second dose (Cmax2)	Capillary blood samples will be collected for the analysis pharmacokinetic parameters. Blood concentrations of MAM01 will be measured using a validated immunoassay.	Pre-and post-dose (IV dosing groups only) at Day 182,186, 189, 196, 210, 238, 266, 294, 322, and 364
Secondary	Concentration at Day 364 (C364)		At Day 364
Secondary	Total AUC from Day 182 - Day 364		From Day182 (post second dose) to Day 364
Secondary	Percentage of participants with antidrug antibodies (ADAs) to MAM01		At Days 1, 28, 84, and 182, 210, 266, and 364