Chemoprophylactic Activity of M5717 in PfSPZ Challenge Model

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: M5717 60 mg; Drug: M5717 80 mg; Drug: Placebo; Drug: M5717 30 mg; Drug: M5717 200 mg; Drug: M5717 100 mg; Drug: Palcebo; Biological: PfSPZ Challenge

Study type: Interventional

Funder types: Industry

Identifiers

NCT04250363

2019-003414-14 (EudraCT Number)

203481/Z/16/Z (Other Grant/Funding Number)

MS201618_0003

Details and patient eligibility

About

The main purpose of this study was to assess the chemoprophylactic activity and dose-exposure-response relationship of single oral dose of M5717 administered after direct intravenous inoculation (DVI) of Plasmodium falciparum sporozoite (PfSPZ) challenge in healthy participants.

Enrollment: 39 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants who are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
• Participants who have a body weight within 50 to 100 kilograms (kg) and body mass index within the range 19.0 to 29.9 kilograms per meter square (kg/m2) (inclusive)
• Male participants, during the study intervention period and for at least 120 days after the day of the study intervention dose (covering a full sperm cycle of 90 days starting after 5 half lives of last dose of study intervention: - refrain from donating sperm plus, either - abstain from intercourse with a woman of childbearing potential (WOCBP) or - use a male condom, when having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of less than (<) 1 percent (%) per year, since a condom may break or leak
• Female participants who are: - not a WOCBP; - at least 1 year post-menopausal (amenorrhea greater than or equal to [>=] 12 months and follicle-stimulating hormone [FSH] >= 40 milli-international units per milliliter [mIU/mL]) at screening; - surgically sterile (bilateral oophorectomy, hysterectomy or bilateral salpingectomy; tubal ligation alone is not sufficient)
• Participants who are capable of giving signed informed consent, which includes compliance with the requirements (including mandatory intake of rescue medication to participants who have been administered the investigational Plasmodium falciparum sporozoite challenge) and restrictions listed in the informed consent form (ICF) and this protocol
• Other protocol defined inclusion criteria could apply

Exclusion criteria

• Participants with 12-Lead electrocardiogram (ECG) outside normal range (QTcF greater than [>] 450 milli seconds [ms], pulse rate [PR] > 215 ms, or QRS > 120 ms) and deemed clinically relevant by the Investigator
• Supine systolic blood pressure > 140 or < 90 millimeter of mercury (mmHg), diastolic blood pressure > 90 or < 50 mmHg, and pulse rate > 90 or < 50 beats per minute (min) at screening and at admission on Day -1 (any abnormal blood pressure or pulse rate results may be repeated once and if the repeat result is within the normal range, it is not considered to have met the exclusion criterion)
• Seropositive for human immunodeficiency virus (HIV) I and II antibody or antigen), hepatitis B virus (HBV; hepatitis B surface antigen [HBsAg]), or hepatitis C virus (HCV; antibody) tests
• Liver function tests above the upper limit of normal (ULN) (> 3 x ULN) the day before DVI / study intervention administration (Day -1)
• History or presence of diagnosed food or known drug allergies (including but not limited to allergy to any of the antimalarial rescue medications to be used in the study), or history of anaphylaxis or other severe allergic reactions
• Participant with a whole blood donation or loss of > 450 mL within 60 days before administration of study drug or unwilling to defer blood donations for 6 months
• Other protocol defined exclusion criteria could apply

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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39 participants in 10 patient groups, including a placebo group

Early liver stage: Pooled Placebo

Placebo Comparator group

Description:

Participants received single dose of placebo matched to M5717 capsule on Day 1 after 2 hours of Plasmodium falciparum Sporozoite (PfSPZ) (3200 sporozoites per injection) intravenous (IV) inoculation administration on Day 1.

Treatment:

Drug: Palcebo

Biological: PfSPZ Challenge

Early liver stage: 30 mg M5717

Experimental group

Description:

Participants received single dose of M5717 30 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 30 mg

Biological: PfSPZ Challenge

Early liver stage: 60 mg M5717

Experimental group

Description:

Participants received single dose of M5717 60 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 60 mg

Biological: PfSPZ Challenge

Drug: M5717 60 mg

Early liver stage: 80 mg M5717

Experimental group

Description:

Participants received single dose of M5717 80 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 80 mg

Biological: PfSPZ Challenge

Early liver stage: 100 mg M5717

Experimental group

Description:

Participants received single dose of M5717 100 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 100 mg

Biological: PfSPZ Challenge

Drug: M5717 100 mg

Early liver stage: 200 mg M5717

Experimental group

Description:

Participants received single dose of M5717 200 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 200 mg

Drug: M5717 200 mg

Biological: PfSPZ Challenge

Late liver stage: Pooled Placebo

Experimental group

Description:

Participants received single dose of placebo matched to M5717 capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Biological: PfSPZ Challenge

Drug: Placebo

Late liver stage: 60 mg M5717

Experimental group

Description:

Participants received single dose of M5717 60 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 60 mg

Biological: PfSPZ Challenge

Drug: M5717 60 mg

Late liver stage: 100 mg M5717

Experimental group

Description:

Participants received single dose of M5717 100 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 100 mg

Biological: PfSPZ Challenge

Drug: M5717 100 mg

Late liver stage: 200 mg M5717

Experimental group

Description:

Participants received single dose of M5717 200 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.

Treatment:

Drug: M5717 200 mg

Drug: M5717 200 mg

Biological: PfSPZ Challenge