EPIC-HOS: A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People With Weakened Immune Systems or at Increased Risk for Poor Outcomes Who Are Hospitalized Due to Severe COVID-19

Sponsor
Pfizer (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05545319
Collaborator
(none)
279
2
10

Study Details

Study Description

Brief Summary

A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People with Weakened Immune Systems or at Increased Risk for Poor Outcomes who are Hospitalized Due to Severe COVID-19

Study Design

Study Type:
Interventional
Anticipated Enrollment :
279 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
AN INTERVENTIONAL EFFICACY AND SAFETY, PHASE 2, DOUBLE-BLIND, 2-ARM STUDY TO INVESTIGATE ORALLY ADMINISTERED NIRMATRELVIR/RITONAVIR COMPARED WITH PLACEBO/RITONAVIR FOR THE TREATMENT OF SEVERE COVID-19 IN HOSPITALIZED PARTICIPANTS WHO ARE IMMUNOCOMPROMISED OR AT INCREASED RISK FOR SEVERE COVID-19 OUTCOMES
Anticipated Study Start Date :
Sep 30, 2022
Anticipated Primary Completion Date :
Jul 14, 2023
Anticipated Study Completion Date :
Jul 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nirmatrelvir/ritonavir

Participants will receive nirmatrelvir/ ritonavir 300 mg/100 mg (or 150 mg/100 mg for participants with eGFR or eCrCl ≥30 to <60 mL/min) q12h from Day 1 through Day 15

Drug: Nirmatrelvir
Participants will receive 2 tablets of nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to <60 mL/min) every 12 hours
Other Names:
  • Paxlovid
  • Drug: Ritonavir
    Participants will receive 1 capsule of ritonavir every 12 hours
    Other Names:
  • Norvir
  • Experimental: Placebo/ritonavir

    Participants will receive placebo 0 mg/ritonavir 100 mg q12h for 15 days.

    Drug: Ritonavir
    Participants will receive 1 capsule of ritonavir every 12 hours
    Other Names:
  • Norvir
  • Drug: Placebo for nirmatrelvir
    Participants will receive 2 tablets of placebo for nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to <60 mL/min) every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in SARS-CoV-2 ribonucleic acid (RNA) level in nasopharyngeal (NP) swabs [Day 1 through Day 5]

      Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.

    Secondary Outcome Measures

    1. Time to sustained clinical recovery. [Day 1 through Day 30]

      Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir treatment on clinical outcomes when added to background usual care, for the treatment of severe COVID-19 in hospitalized participants. Time to sustained clinical recovery is defined as the first day during the 30 days after randomization in which a participant attains a score of 1, 2, or 3 on the 8-point ordinal scale (ie, remains alive and is either not hospitalized or is hospitalized but no longer requires ongoing inpatient medical care for COVID-19) for at least 7 consecutive days.

    2. Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or ECMO [Day 1 through Day 30]

      Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir treatment on clinical outcomes when added to background usual care, for the treatment of severe COVID-19 in hospitalized participants.

    3. Proportion of participants with SARS-CoV-2 RNA <Lower Limit of Quantitation (<LLOQ) (defined as <2.0 log10 copies/mL) in NP swabs [Day 1 through Day 15]

      Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.

    4. Proportion of participants with sustained NP swab SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL) [Day 15 through Day 45]

      To evaluate the effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.

    5. Incidence of Treatment-Related Adverse Events (TEAEs) [Day 1 through Day 45]

      To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants.

    6. Incidence of Adverse Events (AEs) or Serious Adverse Events (SAEs) leading to discontinuations [Day 1 through Day 45]

      To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Meeting 1 of the 2 categories of COVID-19 risk:

    • Category A: Immunocompromised

    • Category B: Non-Immunocompromised, but with ≥2 risk factors

    • Onset of signs/symptoms attributable to COVID-19 ≤10 days prior to the day of randomization for non-immunocompromised participants (Category B).

    • Confirmed SARS-CoV-2 infection as determined by Reverse transcription polymerase chain reaction (RT-PCR) or acceptable test method performed by a health care provider in any specimen collected within 48 hours prior to randomization.

    • Hospitalized for inpatient care for the treatment of clinical manifestations of severe COVID-19.

    • Requirement for oxygen supplementation (via nasal cannula, mask, non-invasive ventilation [NIV] or high flow oxygen) to maintain SpO2 ≥94% at the time of Screening and Randomization.

    Exclusion Criteria:
    • Critical illness, defined by ≥1 of the following:

    • Requirement for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at randomization, or likely to require intermittent mandatory ventilation (IMV) or ECMO within 12 hours of randomization .

    • Multi-organ dysfunction/failure.

    • Hemodynamically unstable, eg. septic shock, cardiac failure or requiring vasopressors.

    • Participant not expected to survive 24 hours from time of randomization.

    • History of severe chronic liver disease

    • Receiving dialysis of any kind or severe renal impairment

    • Use of nirmatrelvir/ritonavir as an outpatient to treat the current COVID-19 related illness ≤7 days of randomization

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT05545319
    Other Study ID Numbers:
    • C4671031
    • 2022-002447-22
    First Posted:
    Sep 19, 2022
    Last Update Posted:
    Sep 19, 2022
    Last Verified:
    Sep 1, 2022

    Study Results

    No Results Posted as of Sep 19, 2022