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

NCT05438602 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: C46710342022-001362-35
• Study Type: interventional
• Target: 158
• Locations: 9 countries
• Sites: 84

Brief Summary

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.

Conditions

COVID-19

Keywords

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Coronavirus disease 2019 (COVID-19); Paxlovid; Nirmatrelvir; Immunocompromised

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Nasopharyngeal (NP) Swab Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) < Lower Limit of Quantitation (LLOQ) From Day 15 to Day 44

  NP swab was collected by healthcare professional (HCP) from participants and were sent to the central laboratory for viral RNA level testing real-time reverse transcriptase-polymerase chain reaction(RT-PCR). Sustained was defined as NP swab SARS-CoV-2 RNA level not \>=2.0 log10 per milliliter (copies/mL) at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA level \<LLOQ (\<2.0 log10 copies/mL).

  From Day 15 to Day 44

Secondary Outcomes (18)

• Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline

  Day 1 through Day 44

• Time to First Sustained NP Swab SARS-CoV-2 RNA < LLOQ for Participants Through Day 44 With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline

  Day 1 through Day 44

• Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24

  Baseline; Days 5, 10, 15, 21, 28, 35, and 44; Weeks 12 and 24

• Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44

  Baseline; Days 5, 10, 15, 21, 28, 35 and 44

• Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44

  Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Study Arms (3)

Nirmatrelvir plus ritonavir for 5 days

EXPERIMENTAL

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

Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir

Nirmatrelvir plus ritonavir for 10 days

EXPERIMENTAL

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

Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir

Nirmatrelvir plus ritonavir for 15 days

EXPERIMENTAL

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

Drug: Nirmatrelvir; Drug: Ritonavir

Interventions

Nirmatrelvir DRUG

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Nirmatrelvir plus ritonavir for 10 days; Nirmatrelvir plus ritonavir for 15 days; Nirmatrelvir plus ritonavir for 5 days

Ritonavir DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

Nirmatrelvir plus ritonavir for 10 days; Nirmatrelvir plus ritonavir for 15 days; Nirmatrelvir plus ritonavir for 5 days

Placebo for nirmatrelvir 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.

Nirmatrelvir plus ritonavir for 10 days; Nirmatrelvir plus ritonavir for 5 days

Placebo for ritonavir 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 plus ritonavir for 5 days

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (84)

CRS Outpatient Services UCSF

San Francisco, California, 94143, United States

Location

UCSF Helen Diller Medical Center at Parnassus Heights

San Francisco, California, 94143, United States

Location

UCSf infectious disease Lab

San Francisco, California, 94143, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

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

Doral, Florida, 33126, United States

Location

Qway Research LLC

Hialeah, Florida, 33010, United States

Location

Premium Medical Research Corp

Miami, Florida, 33126, United States

Location

Global Health Clinical Trials

Miami, Florida, 33135, United States

Location

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

Miami, Florida, 33144, United States

Location

NAPA Research

Pompano Beach, Florida, 33064, United States

Location

Santos Research Center

Tampa, Florida, 33615, United States

Location

Emory University Hospital-Georgia Clinical Research Center

Atlanta, Georgia, 30322, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

National Institute of Health

Bethesda, Maryland, 20892, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Beaumont Infectious Diseases Research

Royal Oak, Michigan, 48073, United States

Location

Revival Research Institute

Sterling Heights, Michigan, 48312, United States

Location

MediSearch Clinical Trials

Saint Joseph, Missouri, 64506, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

South Texas Clinical Research

Corpus Christi, Texas, 78404, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

North Texas Infectious Diseases Consultants, P.A

Dallas, Texas, 75246, United States

Location

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, 76104, United States

Location

Fred Hutchinson Cancer Center - COVID Clinical Research Center

Seattle, Washington, 98109, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Royal Melbourne Hospital - Royal Park Campus

Parkville, Victoria, 3052, Australia

Location

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

Natal, Rio Grande do Norte, 59025050, Brazil

Location

CECIP - Centro de Estudos do Interior Paulista

Jaú, São Paulo, 17201130, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, 15090000, Brazil

Location

IBPClin - Instituto Brasil de Pesquisa Clínica

Rio de Janeiro, 20241-180, Brazil

Location

Instituto Nacional de Infectologia Evandro Chagas

Rio de Janeiro, 21040-360, Brazil

Location

Diagnostic Consultative Center - 1 Lom EOOD

Lom, Montana, 3600, Bulgaria

Location

MHAT Samokov

Samokov, Sofia, 2000, Bulgaria

Location

Military Medical Academy

Sofia, Sofia (stolitsa), 1606, Bulgaria

Location

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

Haskovo, 6305, Bulgaria

Location

MHAT - Heart and Brain

Pleven, 5804, Bulgaria

Location

Medical Center Artmed

Plovdiv, 4000, Bulgaria

Location

MHAT Sveta Karidad EAD

Plovdiv, 4000, Bulgaria

Location

Vancouver Infectious Diseases Centre

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Dawson Clinical Research

Guelph, Ontario, N1H 1B1, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Dr. Anil K. Gupta Medicine Professional Corporation

Toronto, Ontario, M9V 4B4, Canada

Location

Winchester District Memorial Hospital

Winchester, Ontario, K0C 2K0, Canada

Location

INTERMED Groupe Sante

Chicoutimi, Quebec, G7H 7Y8, Canada

Location

Clinique Medicale lActuel

Montreal, Quebec, H2L 4P9, Canada

Location

Diex Recherche Sherbrooke Inc.

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Diex Recherche Trois-Rivieres Inc.

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Medifarma 98 Kft

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

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

Budapest, 1097, Hungary

Location

Semmelweis Egyetem

Budapest, 1122, Hungary

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, 14080, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 66460, Mexico

Location

EME RED Hospitalaria

Mérida, Yucatán, 97000, Mexico

Location

Instituto de Investigaciones Clínicas para la Salud

Durango, 34000, Mexico

Location

Oaxaca Site Management Organization S.C.

Oaxaca City, 68000, Mexico

Location

Instituto Veracruzano en Investigación Clínica S.C.

Veracruz, 91851, Mexico

Location

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

Veracruz, 91900, Mexico

Location

REUMEX s.r.o.

Rimavská Sobota, Banská Bystrica Region, 979 01, Slovakia

Location

Narodny onkologicky ustav

Bratislava, Bratislava Region, 833 10, Slovakia

Location

ALERGIA s.r.o.

Topoľčany, Nitra Region, 955 01, Slovakia

Location

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

Pruské, Trenčín Region, 01852, Slovakia

Location

Univerzitna nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda

Bratislava, 851 07, Slovakia

Location

Univerzitná nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda

Bratislava, 851 07, Slovakia

Location

ARTROMAC n. o.

Košice, 04011, Slovakia

Location

MEDIKOMP, s.r.o

Prešov, 080 01, Slovakia

Location

Plucna ambulancia Hrebenar s.r.o.

Spišská Nová Ves, 052 01, Slovakia

Location

Plucna ambulancia Hrebenar, s.r.o.

Spišská Nová Ves, 052 01, Slovakia

Location

SANARE spol.s.r.o.

Svidník, 089 01, Slovakia

Location

ALERGIA s.r.o.

Topoľčany, 955 01, Slovakia

Location

CHUAC-Complejo Hospitalario Universitario A Coruña

A Coruña, A Coruña [LA Coruña], 15006, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona [barcelona], 08916, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Catalunya [cataluña], 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalunya [cataluña], 08041, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, 28034, Spain

Location

CHUVI- Hospital Alvaro Cunqueiro

Vigo, Pontevedra [pontevedra], 36312, Spain

Location

Hospital Clinico de Valencia

Valencia, Valenciana, Comunitat, 46010, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen de Valme

Seville, 41014, Spain

Location

Hospital Clinico Universitario Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Publications (3)

• 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 Dec;14(12):2763-2783. doi: 10.1007/s40121-025-01228-w. Epub 2025 Oct 14.

  PMID: 41085942 DERIVED

• 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 Nov;25(11):1243-1253. doi: 10.1016/S1473-3099(25)00221-X. Epub 2025 Jul 14.

  PMID: 40675169 DERIVED

• 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.

  PMID: 40592258 DERIVED

Related Links

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

MeSH Terms

Conditions

COVID-19

Interventions

nirmatrelvir; Ritonavir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

For outcome measure data have not been reported for RP separately, since there was 1 participant each in 2 arms (Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day and Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 day), it could have led to re-identification of RP participants. In other sections of results data for RP and MSP have been combined.

Results Point of Contact

• Title: Pfizer Inc.
• Organization: Pfizer ClinicalTrials.gov Call Center

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: June 30, 2022
• Study Start: August 3, 2022
• Primary Completion: July 17, 2023
• Study Completion: November 13, 2023
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (9); BR (5); HU (3); SL (12); US (25); AU (3); ME (7); BU (7); ES (13)