First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: M5717; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03261401

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

MS201618_0013

Details and patient eligibility

About

The primary purpose of this study was to investigate the safety and tolerability of M5717 and to characterize the Pharmacokinetics (PK) /Pharmacodynamic relationship between M5717 PK and parasite clearance in healthy participants following infection with Plasmodium falciparum.

Enrollment: 88 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adult men and women of non-childbearing potential, with total body weight greater than or equal to 50.0 kilogram and body mass index (BMI) between 19.0 kilogram per meter square(kg/m^2) and 29.9 kg/m^2.
• Healthy as assessed by the Investigator with 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 trial evaluation, procedures, or completion.
• Other protocol defined inclusion criteria could apply.

Exclusion criteria

• Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological dermatological, connective tissue diseases or disorders.
• Participants with history of relevant drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other allergic reaction in general, which the Investigator considers may affect the safety of the participant and/or outcome of the trial.
• Participants who have any history of malaria.
• Participants who have participated in a previous malaria vaccine trial.
• Participants who have participated in a previous human malaria challenge trial.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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88 participants in 13 patient groups, including a placebo group

Part A: Placebo (Pooled)

Placebo Comparator group

Description:

Participants received capsules containing 50 milligram (mg) of placebo matched similar to M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.

Treatment:

Drug: Placebo

Part A: Cohort 1 SAD: M5717 50 mg

Experimental group

Description:

Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 2 SAD: M5717 100 mg

Experimental group

Description:

Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 3 SAD: M5717 200 mg

Experimental group

Description:

Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 4 SAD: M5717 400 mg

Experimental group

Description:

Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 5 SAD: M5717 600 mg

Experimental group

Description:

Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 6 SAD: M5717 1000 mg

Experimental group

Description:

Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 7 SAD: M5717 1250 mg

Experimental group

Description:

Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 8 SAD: M5717 1800 mg

Experimental group

Description:

Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part A: Cohort 9 SAD: M5717 2100 mg

Experimental group

Description:

Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part C: Challenge Cohort 2 M5717 150 mg

Experimental group

Description:

Participants received single oral dose of 150 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part C: Challenge Cohort 1 M5717 400 mg

Experimental group

Description:

Participants received single oral dose of 400 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717

Part C: Challenge Cohort 3 M5717 800 mg

Experimental group

Description:

Participants received single oral dose of 800 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Treatment:

Drug: M5717

Drug: M5717