Clinical trial NCT06294912: A Study to Evaluate Antimalarial Activity and Safety of MK-7602 in Healthy Adults (MK-7602-003)
Official title: A Controlled Human Malaria Infection Study to Evaluate the Antimalarial Activity of MK-7602 Against Plasmodium Falciparum Blood Stage Infection in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-03-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* History of convulsion (including intravenous drug or vaccine-induced episodes). A medical history of a single febrile convulsion during childhood is not considered an exclusion criterion.
* 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
* Has clinically significant disease or any condition or disease that might affect drug absorption, distribution, or excretion (eg, gastrectomy, diarrhea)
* Has a medical requirement for intravenous immunoglobulin or blood transfusions
* Has had a major surgery with more than 470 mL of blood loss, lost 1 unit of blood (approximately 470 mL) or undergone blood donation of any volume to the Australian Red Cross Blood Service (Blood Service) or other blood blank within 4 weeks prior to the prestudy screening visit) or during the 8 weeks prior to inoculation
* Has used any corticosteroids, anti-inflammatory drugs (excluding commonly used over-the-counter anti-inflammatory drugs such as ibuprofen, acetylsalicylic acid, diclofenac), immunomodulators or anticoagulants within the past three months
* History of receiving immunosuppressive therapy (including systemic steroids, adrenocorticotrophic hormone, or inhaled steroids) at a dose or duration potentially associated with hypothalamic-pituitary-adrenal axis suppression within the past year from the screening visit
* Has had any vaccination within the last 28 days
* Has participated in another investigational study within 12 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
* History of participation in a previous malaria challenge study or malaria vaccine study.
* Must not have had malaria exposure that is considered by the principal investigator or their delegate to be significant

Primary outcomes:
measure: Parasite reduction ratio (PRR48) (Parts 1 and 2)
timeFrame: 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
measure: Parasite Clearance Half-life (PCt1/2) (Parts 1 and 2)
timeFrame: 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
measure: Parasite Regrowth (Parts 1 and 2)
timeFrame: 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
measure: Part 1 Single dose: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of MK-7602
timeFrame: 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
measure: Part 1 Single dose: Maximum Plasma Concentration (Cmax) of MK-7602
timeFrame: 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
measure: Part 1 Single dose: Concentration at 24 Hours (C24) of MK-7602
timeFrame: 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
measure: Part 1 Single dose: Time to Maximum Plasma Concentration (Tmax) of MK-7602
timeFrame: 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
measure: Part 1 Single dose: Elimination Half-life (t1/2) of MK-7602
timeFrame: 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
measure: Part 2 Multiple dose: Area Under the Curve Time 0 to End of the Dosing Interval (AUC0-tau) of MK-7602
timeFrame: 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
measure: Part 2 Multiple dose: Maximum Plasma Concentration (Cmax) of MK-7602
timeFrame: 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
measure: Part 2 Multiple dose: Time to Maximum Plasma Concentration (Tmax) of MK-7602
timeFrame: 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
measure: Part 2 Multiple dose: Elimination Half-life (t1/2) of MK-7602
timeFrame: 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:
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to Day 45
measure: Number of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to Day 13
Other outcomes:
Locations:
city: South Brisbane
country: Australia
facility: USC Clinical Trials Brisbane (South Bank) ( Site 0001)
state: South Australia
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: