E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus Disease 2019 (COVID-19) |
|
E.1.1.1 | Medical condition in easily understood language |
Coronavirus infection disease |
|
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 | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084460 |
E.1.2 | Term | COVID-19 treatment |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 |
To compare the efficacy of PF-07321332/ritonavir to placebo for the treatment of COVID-19 in nonhospitalized symptomatic adult participants with COVID-19 who are at increased risk of progression to severe disease. |
|
E.2.2 | Secondary objectives of the trial |
-To describe the safety and tolerability of PF-07321332/ritonavir relative to placebo in the treatment of nonhospitalized symptomatic adult participants with COVID-19 who are at increased risk of progression to severe disease. - To compare the efficacy of PF 07321332/ritonavir to placebo for the treatment of COVID-19 in nonhospitalized symptomatic adult participants with COVID 19 who are at increased risk of progression to severe disease. -To compare PF-07321332/ritonavir to placebo for all-cause mortality in nonhospitalized symptomatic adult participants with COVID-19 who are at increased risk of progression to severe disease. -To determine the PK of PF-07321332 in nonhospitalized symptomatic adult participants with COVID 19 who are at increased risk of progression to severe disease. *details of remaining objectives in Protocol |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants ≥18 years of age (or the minimum country-specific age of consent if >18) at the time of the Screening Visit. - WOCBP may be enrolled. - All fertile participants must agree to use a highly effective method of contraception. Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. 2.Confirmed SARS-CoV-2 infection as determined by RT-PCR in any specimen collected within 5 days prior to randomization. Note: RT-PCR is the preferred method; however, with evolving approaches to confirmation of SARS-CoV-2 infection, other molecular or antigen tests that detect viral RNA or protein are allowed. The test result must be available to confirm eligibility. Participants may be enrolled based on positive results of a rapid SARS-CoV-2 antigen test performed at screening. 3.Initial onset of signs/symptoms attributable to COVID-19 within 5 days prior to the day of randomization and at least 1 of the specified signs/symptoms attributable to COVID-19 present on the day of randomization (see Appendix 9 for criteria). 4.Has at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19 including: - ≥60 years of age; - BMI >25; - Current smoker (cigarette smoking within the past 30 days) and history of at least 100 lifetime cigarettes; - Immunosuppressive disease (eg, bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications: o Has received corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days within 30 days prior to study entry. o Has received treatment with biologics (eg, infliximab, ustekinumab), immunomodulators (eg, methotrexate, 6MP, azathioprine) or cancer chemotherapy within 90 days prior to study entry. o HIV infection with CD4 cell count <200 mm3 and a viral load less than 400 copies/mL - Chronic lung disease (if asthma, requires daily prescribed therapy); - Known diagnosis of hypertension; - CVD, defined as history of any of the following: myocardial infarction, stroke, TIA, HF, angina with prescribed nitroglycerin, CABG, PCI, carotid endarterectomy, and aortic bypass; - Type 1 or Type 2 diabetes mellitus; - CKD provided the participant does not meet Exclusion Criterion 5; - Sickle cell disease; - Neurodevelopmental disorders (eg, cerebral palsy, Down’s syndrome) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes and severe congenital anomalies); - Active cancer, other than localized skin cancer, including those requiring treatment as long as the treatment is not among the prohibited medications that must be administered/continued during the trial period; - Medical-related technological dependence (eg, CPAP [not related to COVID-19]). 5. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 6. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. |
|
E.4 | Principal exclusion criteria |
1. History of hospitalization for the medical treatment of COVID-19. 2. Current need for hospitalization or anticipated need for hospitalization within 48 hours after randomization in the clinical opinion of the site investigator (see Section 8.1.2.) 3. Prior to current disease episode, any confirmed SARS-CoV-2 infection, as determined by a molecular test (antigen or nucleic acid) from any specimen collection. 4. Known medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic or active hepatitis B or C infection, primary biliary cirrhosis, Child-Pugh Class B or C, or acute liver failure. 5. Receiving dialysis or have known moderate to severe renal impairment [ie, eGFR <45 mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula] 6. Known HIV infection with a viral load greater than 400 copies/mL or taking prohibited medications for HIV treatment from known medical history within past 6 months of the screening visit) (Appendix 8). 7. Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention. 8. Any comorbidity requiring hospitalization and/or surgery within 7 days prior to study entry, or that is considered life threatening within 30 days prior to study entry, as determined by the investigator. 9. History of hypersensitivity or other contraindication to any of the components of the study intervention, as determined by the investigator. 10. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 11. Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations may be associated with serious and/or life-threatening events during treatment and for 4 days after the last dose of PF-07321332/ritonavir (See Appendix 8). 12. Concomitant use of any medications or substances that are strong inducers of CYP3A4 are prohibited within 28 days prior to first dose of PF-07321332/ritonavir and during study treatment (see Appendix 8). 13. Has received or is expected to receive convalescent COVID-19 plasma. 14. Has received or is expected to receive any dose of a SARS-CoV-2 vaccine before the Day 34 visit. 15. Is unwilling to abstain from participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 therapeutics, through the long-term follow-up visit. 16. Previous administration with any investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). 17. Known prior participation in this trial or other trial involving PF-07321332. 18. Known history of any of the following abnormalities in clinical laboratory tests (within past 6 months of the screening visit): - AST or ALT level ≥2.5 X ULN; - Total bilirubin ≥2 X ULN (≥3 X ULN for Gilbert’s syndrome); - Absolute neutrophil count <1000/mm3. - GFR <45 mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula30 Note: If the investigator suspects the participant may have any of the above laboratory values, confirmatory tests should be performed at screening to confirm eligibility before the first dose of study intervention. See Appendix 2 for more details. 19. Oxygen saturation of <92% on room air obtained at rest within 24 hours prior to randomization. Note: for a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, oxygen saturation should be measured while on their standard home oxygen supplementation. 20. Females who are pregnant or breastfeeding. 21. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants with COVID-19 related hospitalization or death from any cause through Day 28. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Incidence of TEAEs. - Incidence of SAEs and AEs leading to discontinuations. - Proportion of participants with COVID-19-related hospitalization or death from any cause through Day 28. - Time (days) to sustained alleviation of all targeted signs/symptoms through Day 28. - Proportion of participants with severe signs/symptoms attributed to COVID-19 through Day 28. - Time (days) to sustained resolution of all targeted signs/symptoms through Day 28. - Duration of each targeted COVID 19 sign/symptom. - Progression to a worsening status in 1 or more self reported COVID 19 associated symptoms through Day 28. - Proportion of participants with a resting peripheral oxygen saturation ≥95% at Days 1 and 5. - Proportion of participants with death (all cause) through Week 24. - PF 07321332 PK in plasma and whole blood (if feasible). - Viral titers measured via RT-PCR in nasal swabs over time. - Number of COVID-19 related medical visits through Day 28. - Number of days in hospital and ICU stay in participants with COVID-19 related hospitalization. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Argentina |
Brazil |
Bulgaria |
China |
Colombia |
Czechia |
Hungary |
India |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Peru |
Poland |
Puerto Rico |
Russian Federation |
South Africa |
Spain |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 2 |