A Study to Learn About the Study Medicines (Nirmatrelvir Plus Ritonavir) in People Aged 12 Years or Older With COVID-19 and a Compromised Immune System

NCT ID: NCT05438602

Last Updated: 2024-09-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-03

Study Completion Date

2023-11-13

Brief Summary

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The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called Nirmatrelvir/Ritonavir) for the possible treatment of COVID-19.

Patients with COVID-19 who have more difficulty in fighting against infections have a higher chance of severe illness. Such patients may benefit from longer treatment durations compared to the standard treatment regimen.

The study is seeking participants who:

* Have a confirmed COVID-19 infection
* Are Immunocompromised
* Experience onset of signs/symptoms attributable to the current COVID-19 infection within 5 days prior to screening and ≥1 signs/symptoms attributable to COVID-19 present on the day of randomization.

In addition, this study will also evaluate the efficacy and safety of a second treatment course of nirmatrelvir/ritonavir in people who experience that their COVID-19 is flaring up within 14 days of having taken a 5-day treatment course of nirmatrelvir/ritonavir.

For this group, the study is seeking participants who:

* Have a confirmed COVID-19 infection
* Experience a worsening of signs/symptoms after completing an initial 5-day course of nirmatrelvir/ritonavir
* The worsening of COVID-19 symptoms must occur within 14 days after completion of the initial 5-day course of nirmatrelvir/ritonavir
* Are Immunocompromised
* Experience onset of signs/symptoms attributable to the current COVID-19 infection within 48 hours prior to screening and ≥1 signs/symptoms attributable to COVID-19 present on the day of randomization.

All participants will be taking the study medicine for either 5, 10, or 15 days. The study medication will be taken by mouth 2 times a day. Participants will take part in this study for about 24 weeks. The first dose of study medication is taken at the study site and the rest at home. Selected participants will need to visit the study site at least 10 times during the study.

Detailed Description

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Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Nirmatrelvir plus ritonavir for 5 days

Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 10 days

Group Type EXPERIMENTAL

Nirmatrelvir

Intervention Type DRUG

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

Placebo for nirmatrelvir

Intervention Type DRUG

Participants will receive 2 tablets of placebo for nirmatrelvir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Placebo for ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of placebo for ritonavir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Nirmatrelvir plus ritonavir for 10 days

Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 10 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 5 days

Group Type EXPERIMENTAL

Nirmatrelvir

Intervention Type DRUG

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

Placebo for nirmatrelvir

Intervention Type DRUG

Participants will receive 2 tablets of placebo for nirmatrelvir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Placebo for ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of placebo for ritonavir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Nirmatrelvir plus ritonavir for 15 days

Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 15 days.

Group Type EXPERIMENTAL

Nirmatrelvir

Intervention Type DRUG

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

Interventions

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Nirmatrelvir

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Intervention Type DRUG

Ritonavir

Participants will receive 1 capsule of ritonavir every 12 hours

Intervention Type DRUG

Placebo for nirmatrelvir

Participants will receive 2 tablets of placebo for nirmatrelvir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Intervention Type DRUG

Placebo for ritonavir

Participants will receive 1 capsule of placebo for ritonavir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participants aged 12 years or older and weighing ≥40 kg at screening.
* Immunocompromised
* ≥1 signs/symptoms attributable to COVID-19 present on the day of randomization.

Participants for the main population must have:

\- Confirmed SARS-CoV-2 infection as determined by RT-PCR or other acceptable test method in any specimen collected within 5 days prior to randomization for the main study population.

Participants form the rebound population must have:

\- Confirmed SARS-CoV-2 infection as determined by RT-PCR or rapid antigen testing in any specimen collected within 24h prior to randomization and collected within 14 days after the completion of the initial 5-day treatment course of nirmatrelvir/ritonavir for the population with rebound.

Exclusion Criteria

* Current need for hospitalization or anticipated need for hospitalization within 24 h after randomization
* Known medical history of active liver disease
* Known HIV infection with a viral load \>400 copies/mL or taking prohibited medications for human immunodeficiency virus (HIV)
* Receiving dialysis or have known age-specific estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCrCl) \<30 mL/min/1.73 m2 at screening as measured by a serum creatinine point of care device
* Oxygen saturation of \<92% on room air obtained at rest within 24 hours prior to randomization
* Current use of any prohibited concomitant medication(s)
* Females who are pregnant and \<14 weeks gestation
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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CRS Outpatient Services UCSF

San Francisco, California, United States

Site Status

UCSF Helen Diller Medical Center at Parnassus Heights

San Francisco, California, United States

Site Status

UCSf infectious disease Lab

San Francisco, California, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

I.V.A.M. Clinical & Investigational Center

Doral, Florida, United States

Site Status

Qway Research LLC

Hialeah, Florida, United States

Site Status

Premium Medical Research Corp

Miami, Florida, United States

Site Status

Global Health Clinical Trials

Miami, Florida, United States

Site Status

I.V.A.M. Clinical & Investigational Center

Miami, Florida, United States

Site Status

NAPA Research

Pompano Beach, Florida, United States

Site Status

Santos Research Center

Tampa, Florida, United States

Site Status

Emory University Hospital-Georgia Clinical Research Center

Atlanta, Georgia, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

The Emory Clinic

Atlanta, Georgia, United States

Site Status

National Institute of Health

Bethesda, Maryland, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Beaumont Infectious Diseases Research

Royal Oak, Michigan, United States

Site Status

Revival Research Institute

Sterling Heights, Michigan, United States

Site Status

MediSearch Clinical Trials

Saint Joseph, Missouri, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

South Texas Clinical Research

Corpus Christi, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, P.A

Dallas, Texas, United States

Site Status

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, United States

Site Status

Fred Hutchinson Cancer Center - COVID Clinical Research Center

Seattle, Washington, United States

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

The Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Royal Melbourne Hospital - Royal Park Campus

Parkville, Victoria, Australia

Site Status

Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCLIN/RN

Natal, Rio Grande do Norte, Brazil

Site Status

CECIP - Centro de Estudos do Interior Paulista

Jaú, São Paulo, Brazil

Site Status

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status

IBPClin - Instituto Brasil de Pesquisa Clínica

Rio de Janeiro, , Brazil

Site Status

Instituto Nacional de Infectologia Evandro Chagas

Rio de Janeiro, , Brazil

Site Status

Diagnostic Consultative Center - 1 Lom EOOD

Lom, Montana, Bulgaria

Site Status

MHAT Samokov

Samokov, Sofia, Bulgaria

Site Status

Military Medical Academy

Sofia, Sofia (stolitsa), Bulgaria

Site Status

Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD

Haskovo, , Bulgaria

Site Status

MHAT - Heart and Brain

Pleven, , Bulgaria

Site Status

Medical Center Artmed

Plovdiv, , Bulgaria

Site Status

MHAT Sveta Karidad EAD

Plovdiv, , Bulgaria

Site Status

Vancouver Infectious Diseases Centre

Vancouver, British Columbia, Canada

Site Status

Dawson Clinical Research

Guelph, Ontario, Canada

Site Status

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Site Status

Dr. Anil K. Gupta Medicine Professional Corporation

Toronto, Ontario, Canada

Site Status

Winchester District Memorial Hospital

Winchester, Ontario, Canada

Site Status

INTERMED Groupe Sante

Chicoutimi, Quebec, Canada

Site Status

Clinique Medicale lActuel

Montreal, Quebec, Canada

Site Status

Diex Recherche Sherbrooke Inc.

Sherbrooke, Quebec, Canada

Site Status

Diex Recherche Trois-Rivieres Inc.

Sherbrooke, Quebec, Canada

Site Status

Medifarma 98 Kft

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Site Status

Dél-Pesti Centrumkórház Országos Hematológiai és infektológiai intézet, Szent László telep

Budapest, , Hungary

Site Status

Semmelweis Egyetem

Budapest, , Hungary

Site Status

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, Mexico

Site Status

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, Mexico

Site Status

EME RED Hospitalaria

Mérida, Yucatán, Mexico

Site Status

Instituto de Investigaciones Clínicas para la Salud

Durango, , Mexico

Site Status

Oaxaca Site Management Organization S.C.

Oaxaca City, , Mexico

Site Status

Instituto Veracruzano en Investigación Clínica S.C.

Veracruz, , Mexico

Site Status

FAICIC S. de R.L. de C.V.

Veracruz, , Mexico

Site Status

REUMEX s.r.o.

Rimavská Sobota, Banská Bystrica Region, Slovakia

Site Status

Narodny onkologicky ustav

Bratislava, Bratislava Region, Slovakia

Site Status

ALERGIA s.r.o.

Topoľčany, Nitra Region, Slovakia

Site Status

MUDr. Viliam Cibik, PhD., s.r.o.

Pruské, Trenčín Region, Slovakia

Site Status

Univerzitna nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda

Bratislava, , Slovakia

Site Status

Univerzitná nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda

Bratislava, , Slovakia

Site Status

ARTROMAC n. o.

Košice, , Slovakia

Site Status

MEDIKOMP, s.r.o

Prešov, , Slovakia

Site Status

Plucna ambulancia Hrebenar s.r.o.

Spišská Nová Ves, , Slovakia

Site Status

Plucna ambulancia Hrebenar, s.r.o.

Spišská Nová Ves, , Slovakia

Site Status

SANARE spol.s.r.o.

Svidník, , Slovakia

Site Status

ALERGIA s.r.o.

Topoľčany, , Slovakia

Site Status

CHUAC-Complejo Hospitalario Universitario A Coruña

A Coruña, A Coruña [LA Coruña], Spain

Site Status

Hospital Germans Trias i Pujol

Badalona, Barcelona [barcelona], Spain

Site Status

Hospital Clínic de Barcelona

Barcelona, Catalunya [cataluña], Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalunya [cataluña], Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, Spain

Site Status

CHUVI- Hospital Alvaro Cunqueiro

Vigo, Pontevedra [pontevedra], Spain

Site Status

Hospital Clinico de Valencia

Valencia, Valenciana, Comunitat, Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Virgen de Valme

Seville, , Spain

Site Status

Hospital Clinico Universitario Valencia

Valencia, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Countries

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United States Australia Brazil Bulgaria Canada Hungary Mexico Slovakia Spain

References

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Mokgokong R, Cislo P, Tudone E, Weinstein E, Cappelleri JC. Symptom Alleviation/Resolution and Returns to Usual Health/Activities in Immunocompromised Adults with COVID-19 Treated with Nirmatrelvir-Ritonavir: Results from the EPIC-IC Trial. Infect Dis Ther. 2025 Oct 14. doi: 10.1007/s40121-025-01228-w. Online ahead of print.

Reference Type DERIVED
PMID: 41085942 (View on PubMed)

Weinstein E, Paredes R, Gardner A, Almas M, Baniecki ML, Guan S, Tudone E, Antonucci S, Gregg K, Garcia-Vidal C, Camacho-Ortiz A, Wisemandle W, Terra SG, Liu S, Aberg JA, Rana MM, Corey L, Ford ES, Hammond J, Rusnak J. Extended nirmatrelvir-ritonavir treatment durations for immunocompromised patients with COVID-19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2025 Jul 14:S1473-3099(25)00221-X. doi: 10.1016/S1473-3099(25)00221-X. Online ahead of print.

Reference Type DERIVED
PMID: 40675169 (View on PubMed)

Baniecki ML, Guan S, Rai DK, Yang Q, Lee JT, Hao L, Weinstein E, Hyde C, Cardin RD, Soares H, Hammond J. Integrated virologic analysis of resistance to nirmatrelvir/ritonavir in individuals across four phase 2/3 clinical studies for the treatment of COVID-19. EBioMedicine. 2025 Aug;118:105819. doi: 10.1016/j.ebiom.2025.105819. Epub 2025 Jun 30.

Reference Type DERIVED
PMID: 40592258 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4671034

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

Other Identifiers

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2022-001362-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C4671034

Identifier Type: -

Identifier Source: org_study_id

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