A Study to Evaluate Antimalarial Activity and Safety of MK-7602 in Healthy Adults (MK-7602-003)

NCT06294912 | Completed Phase 1

• 2 other identifiers: 7602-003MK-7602-003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the antimalarial activity, pharmacokinetics, and safety of MK-7602 in healthy adults following Plasmodium falciparum (P. falciparum) infection.

Conditions

Malaria

Outcome Measures

Primary Outcomes (12)

• Parasite reduction ratio (PRR48) (Parts 1 and 2)

  PRR48 is the logarithm of the parasite reduction ratio per 48 hours determined from parasitemia data from time 0 to time 48 hours. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the PRR48.

  Pre-inoculation on Day 0, once daily Days 4 to 7, pre-dose of MK-7602 on Day 8, post-first dose of MK-7602 at 2, 4, 8, 12, 16, 24, 30, 36, 48, 54, 60, 72, (78 Part 2 only), 84, and 96 hours, and once daily Days 13, 15, 17, 20, 22, 24, 27, 29, 31, and 34

• Parasite Clearance Half-life (PCt1/2) (Parts 1 and 2)

  PCt1/2 is the half-life of the log-linear portion of the parasite clearance curve. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the PCt1/2.

  Pre-inoculation on Day 0, once daily Days 4 to 7, pre-dose of MK-7602 on Day 8, post-first dose of MK-7602 at 2, 4, 8, 12, 16, 24, 30, 36, 48, 54, 60, 72, (78 Part 2 only), 84, and 96 hours, and once daily Days 13, 15, 17, 20, 22, 24, 27, 29, 31, and 34

• Parasite Regrowth (Parts 1 and 2)

  Parasite regrowth is defined as initial parasite clearance followed by asexual parasite regrowth above 5,000 parasites/mL. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the parasite regrowth.

  Pre-inoculation on Day 0, once daily Days 4 to 7, pre-dose of MK-7602 on Day 8, post-first dose of MK-7602 at 2, 4, 8, 12, 16, 24, 30, 36, 48, 54, 60, 72, (78 Part 2 only), 84, and 96 hours, and once daily Days 13, 15, 17, 20, 22, 24, 27, 29, 31, and 34

• Part 1 Single dose: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-inf for Part 1.

  Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 1 Single dose: Maximum Plasma Concentration (Cmax) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax for Part 1.

  Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 1 Single dose: Concentration at 24 Hours (C24) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the C24 for Part 1.

  Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 1 Single dose: Time to Maximum Plasma Concentration (Tmax) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax for Part 1.

  Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 1 Single dose: Elimination Half-life (t1/2) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t1/2 for Part 1.

  Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 2 Multiple dose: Area Under the Curve Time 0 to End of the Dosing Interval (AUC0-tau) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-tau for Part 2.

  Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 2 Multiple dose: Maximum Plasma Concentration (Cmax) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax for Part 2.

  Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 2 Multiple dose: Time to Maximum Plasma Concentration (Tmax) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax for Part 2.

  Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

• Part 2 Multiple dose: Elimination Half-life (t1/2) of MK-7602

  Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t½ for Part 2.

  Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22

Secondary Outcomes (2)

• Number of Participants Who Experience an Adverse Event (AE)

  Up to Day 45

• Number of Participants Who Discontinue Study Intervention Due to an AE

  Up to Day 13

Study Arms (8)

Panel A: MK-7602 Single dose Part 1

EXPERIMENTAL

Participants are inoculated with Plasmodium falciparum (P. falciparum). Panel A participants receive MK-7602 as a single oral dose. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel B: MK-7602 Single dose Part 1

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel B participants receive MK-7602 as a single oral dose. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel C: MK-7602 Single dose Part 1

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel C participants receive MK-7602 as a single oral dose. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel D: MK-7602 Single dose Part 1

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel D participants receive MK-7602 as a single oral dose. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel E: MK-7602 Single dose Part 1

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel E participants receive MK-7602 as a single oral dose. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel F: MK-7602 Multiple dose Part 2

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel F participants receive MK-7602 at multiple oral doses. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel G: MK-7602 Multiple dose Part 2

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel G participants receive MK-7602 at multiple oral doses. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Panel H: MK-7602 Multiple dose Part 2

EXPERIMENTAL

Participants are inoculated with P. falciparum. Panel H participants receive MK-7602 at multiple oral doses. Participants will receive artemether/lumefantrine oral tablets as definitive antimalarial treatment. Additional definitive antimalarial treatment may be administered at the investigator's discretion.

Other: Plasmodium falciparum; Drug: MK-7602; Drug: Artemether/lumefantrine; Drug: Primaquine; Drug: Artesunate; Drug: Atovaquone/proguanil

Interventions

Plasmodium falciparum OTHER

Parasite inoculation administered by intravenous (IV) infusion as the challenge agent

Also known as: P. falciparum

Panel A: MK-7602 Single dose Part 1; Panel B: MK-7602 Single dose Part 1; Panel C: MK-7602 Single dose Part 1; Panel D: MK-7602 Single dose Part 1; Panel E: MK-7602 Single dose Part 1; Panel F: MK-7602 Multiple dose Part 2; Panel G: MK-7602 Multiple dose Part 2; Panel H: MK-7602 Multiple dose Part 2

MK-7602 DRUG

Capsules to be administered orally.

Panel A: MK-7602 Single dose Part 1; Panel B: MK-7602 Single dose Part 1; Panel C: MK-7602 Single dose Part 1; Panel D: MK-7602 Single dose Part 1; Panel E: MK-7602 Single dose Part 1; Panel F: MK-7602 Multiple dose Part 2; Panel G: MK-7602 Multiple dose Part 2; Panel H: MK-7602 Multiple dose Part 2

Artemether/lumefantrine DRUG

Tablets to be administered orally as definitive antimalarial treatment.

Also known as: Riamet®; Coartem®

Panel A: MK-7602 Single dose Part 1; Panel B: MK-7602 Single dose Part 1; Panel C: MK-7602 Single dose Part 1; Panel D: MK-7602 Single dose Part 1; Panel E: MK-7602 Single dose Part 1; Panel F: MK-7602 Multiple dose Part 2; Panel G: MK-7602 Multiple dose Part 2; Panel H: MK-7602 Multiple dose Part 2

Primaquine DRUG

Tablets to be administered orally as definitive antimalarial treatment.

Also known as: Primacin®

Panel A: MK-7602 Single dose Part 1; Panel B: MK-7602 Single dose Part 1; Panel C: MK-7602 Single dose Part 1; Panel D: MK-7602 Single dose Part 1; Panel E: MK-7602 Single dose Part 1; Panel F: MK-7602 Multiple dose Part 2; Panel G: MK-7602 Multiple dose Part 2; Panel H: MK-7602 Multiple dose Part 2

Artesunate DRUG

Intravenous (IV) infusion to be administered as definitive antimalarial treatment.

Panel A: MK-7602 Single dose Part 1; Panel B: MK-7602 Single dose Part 1; Panel C: MK-7602 Single dose Part 1; Panel D: MK-7602 Single dose Part 1; Panel E: MK-7602 Single dose Part 1; Panel F: MK-7602 Multiple dose Part 2; Panel G: MK-7602 Multiple dose Part 2; Panel H: MK-7602 Multiple dose Part 2

Atovaquone/proguanil DRUG

Tablets to be administered orally as definitive antimalarial treatment.

Also known as: Malarone ®

Panel A: MK-7602 Single dose Part 1; Panel B: MK-7602 Single dose Part 1; Panel C: MK-7602 Single dose Part 1; Panel D: MK-7602 Single dose Part 1; Panel E: MK-7602 Single dose Part 1; Panel F: MK-7602 Multiple dose Part 2; Panel G: MK-7602 Multiple dose Part 2; Panel H: MK-7602 Multiple dose Part 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Is in good health
• Has a body mass index (BMI) between 18 and 32 kg/m2, inclusive
• For participant assigned male sex at birth: If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 90 days after the last dose of MK-7602: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom plus additional contraceptive method
• For participant assigned female sex at birth: EITHER be a person of nonchildbearing potential (PONCBP) OR must use a highly effective contraceptive method or be abstinent during the intervention period and for at least 10 days after the last dose of study intervention
• Must provide confirmation of not living alone (at any stage from inoculation day until the end of the study). A participant who lives alone may be included on a case-by-case basis.
• Agrees to refrain from eating food containing poppy seeds for 48 hours prior to screening, malaria inoculation, and MK-7602 administration
• History of clinically significant clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Is mentally or legally incapacitated or has a history of clinically significant psychiatric disorder
• History of cancer (malignancy)
• History of malaria
• History of splenectomy
• History of ever receiving a blood transfusion
• History of recurrent headache (eg, tension-type, cluster or migraine) with a frequency of ≥2 episodes per month on average and severe enough to require medical therapy, during the 5 years preceding the screening visit
• Has presence of clinically significant infectious disease or fever (eg, sublingual temperature ≥38.5 degrees Celsius) within the 5 days prior to inoculation
• Has evidence of acute illness within the 4 weeks prior to screening that the Investigator deems may compromise participant safety

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

USC Clinical Trials Brisbane (South Bank) ( Site 0001)

South Brisbane, South Australia, 4101, Australia

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination; Primaquine; Artesunate; atovaquone, proguanil drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 6, 2024
• Study Start: April 18, 2024
• Primary Completion: January 6, 2025
• Study Completion: January 6, 2025
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)