E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084382 |
E.1.2 | Term | Coronavirus disease 2019 |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the efficacy of MK-4482 compared to placebo as assessed by the percentage of participants who are hospitalized and/or die from randomization through Day 29. 2. To evaluate the safety and tolerability of MK-4482 compared to placebo.
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of MK-4482 compared to placebo as assessed by time to sustained resolution or improvement, and time to progression of each targeted self-reported sign/symptom of COVID-19 from randomization through Day 29. 2. To evaluate the efficacy of MK-4482 compared to placebo as assessed by the odds of a more favorable response on the World Health Organization (WHO) 11-point ordinal scale on Day 3, End of Therapy (EOT), Day 10, Day 15, and Day 29.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Peripheral Blood Mononuclear Cells (PBMC) PK Sub-study |
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E.3 | Principal inclusion criteria |
1. Has documentation of laboratory-confirmed SARS-CoV-2 infection with sample collection ≤5 days prior to the day of randomization. 2. Had initial onset of signs/symptoms attributable to COVID-19 for ≤5 days prior to the day of randomization and at least 1 of the following signs/symptoms attributable to COVID-19 on the day of randomization: -Cough -Sore throat -Nasal congestion -Runny nose -Shortness of breath or difficulty breathing with exertion -Muscle or body aches -Fatigue -Fever > 38.0◦C -Chills -Headache -Nausea -Vomiting -Diarrhea -Loss of smell -Loss of taste 3. Has mild or moderate COVID-19 (refer to protocol to determine disease severity at randomization). 4. Has at least 1 characteristic or underlying medical condition associated with an increased risk of severe illness from COVID-19 (refer to protocol to determine disease severity at randomization and to determine if the participant has a characteristic or underlying medical condition associated with an increased risk of severe illness from COVID- 19.). 5. Is willing and able to take oral medication. 6. Is male or female ≥18 years of age, at the time of providing informed consent. 7. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 4 days after the last dose of study intervention: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below: Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and using a contraceptive method that is highly effective (a low user dependency method OR a user dependent method in combination with barrier method), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a longterm and persistent basis), for at least 4 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • If contraceptives are interrupted as standard of care management of COVID-19 patients and resumed at a later time point, such as at hospital discharge, then abstinence must be practiced for the defined period of back-up contraception per the contraceptive product labeling. After this period, contraceptive use must adhere to the Protocol. 9. Participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR. However, the participant may participate in the study without participating in FBR. |
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E.4 | Principal exclusion criteria |
1. Is currently hospitalized or is expected to need hospitalization for COVID-19 within 48 hours of randomization. 2. Is on dialysis or has reduced eGFR <30 mL/min/1.73 m2 (by the MDRD equation). 3. Has any of the following conditions: -HIV with a recent VL >50 copies/mL (regardless of CD4 count) or an AIDS-defining illness in the past 6 months. -A neutrophilic granulocyte absolute count <500/mm3 4. Has a history of HBV or HCV infection with any of the following: • Cirrhosis • End-stage liver disease • Hepatocellular carcinoma • AST and/or ALT >3X upper limit of normal at screening 5. Has a platelet count <100,000/μL or received a platelet transfusion in the 5 days prior to randomization. 6. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. 7. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments including but not limited to: -Participants who are not expected to survive longer than 48 hours after randomization, or -Participants with a recent history of mechanical ventilation, or -Participants with conditions that could limit gastrointestinal absorption of capsule contents. 8. Is taking or is anticipated to require any prohibited therapies as outlined in Protocol. 9. Is unwilling to abstain from participating in another interventional clinical study through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics. 10. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Percentage of participants who are hospitalized and/or die 2. Percentage of participants with an adverse event (AE) 3. Percentage of participants who discontinued study intervention due to an AE |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 29 Days 2. Up to 7 Months 3. Up to 6 Days
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E.5.2 | Secondary end point(s) |
1. Time to sustained resolution or improvement of each targeted COVID-19 sign/symptom 2. Time to progression of targeted COVID-19 signs/symptoms 3. WHO 11-point outcomes score on a scale |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to 29 Days 2. Up to 29 Days 3. Up to 29 Days |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
Chile |
Colombia |
Israel |
Mexico |
Philippines |
Russian Federation |
South Africa |
Ukraine |
United States |
France |
Germany |
Italy |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |