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 (EPIC-HOS)

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

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 Overview

• Status: Withdrawn
• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); Coronavirus Disease 2019 (COVID-19); Immunocompromised; Hospitalization; Child, Hospitalized
• Intervention / Treatment: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Haskovo, Bulgaria, 6304
    • Multiprofile Hospital for Active Treatment - Haskovo AD
  • Haskovo, Bulgaria, 6305
    • Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD
  • Pernik, Bulgaria, 2300
    • "Specialized Hospital for Active Treatment of Lung Diseases - Pernik" EOOD
  • Pleven, Bulgaria, 5804
    • MHAT - Heart and Brain
  • Pleven, Bulgaria, 5800
    • "University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
  • Plovdiv, Bulgaria, 4003
    • "Multiprofile Hospital for Active Treatment - Medical Complex Sveti Ivan Rilski" EOOD
  • Stara Zagora, Bulgaria, 6003
    • UMHAT "Prof. Dr. Stoyan Kirkovich"AD
  • Montana
    • Lom, Montana, Bulgaria, 3600
      • Multiprofile Hospital for Active Treatment - Sveti Nikolay Chudotvoretz
  • Vratsa
    • Kozloduy, Vratsa, Bulgaria, 3320
      • Multiprofile Hospital for Active Treatment Sv. Ivan Rilski - Kozloduy EOOD
• United States
  • New York
    • Cooperstown, New York, United States, 13326
      • Bassett Medical Center
    • New York, New York, United States, 10037
      • Harlem Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nirmatrelvir/ritonavir; Participants will receive nirmatrelvir/ ritonavir 300 mg/100 mg (or 150 mg/100 mg for participants with estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCrCl) ≥30 to <60 mL/min) every 12 hours 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 every 12 hours 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal (NP) swabs	Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.	Day 1 through Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to sustained clinical recovery.	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.	Day 1 through Day 30
Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)	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.	Day 1 through Day 30
Proportion of participants with SARS-CoV-2 RNA <Lower Limit of Quantitation (<LLOQ) (defined as <2.0 log10 copies/mL) in NP swabs	Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.	Day 1 through Day 15
Proportion of participants with sustained NP swab SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL)	To evaluate the effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.	Day 15 through Day 45
Incidence of Treatment-Related Adverse Events (TEAEs)	To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants.	Day 1 through Day 45
Incidence of Adverse Events (AEs) or Serious Adverse Events (SAEs) leading to discontinuations	To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants.	Day 1 through Day 45

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 13, 2022
• Primary Completion (Anticipated): September 21, 2023
• Study Completion (Anticipated): January 6, 2024

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus Infections; Respiratory Tract Diseases; Anti-Infective Agents; Pneumonia; COVID-19; Antiviral Agents; Virus Diseases; Lung Diseases; HIV Protease Inhibitors; Respiratory Tract Infections; Infections; Pneumonia, Viral; Coronaviridae Infections; Nidovirales Infections; Ribonucleic acid (RNA) virus Infections; Ritonavir; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms; Pharmacological Action; Anti-human immunodeficiency virus (HIV) Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Paxlovid; Nirmatrelvir
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: C4671031; 2022-002447-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes