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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05438602
Recruitment Status : Completed
First Posted : June 30, 2022
Last Update Posted : January 25, 2024
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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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.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Nirmatrelvir Drug: Ritonavir Drug: Placebo for nirmatrelvir Drug: Placebo for ritonavir Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 157 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: AN INTERVENTIONAL EFFICACY AND SAFETY, PHASE 2, RANDOMIZED, DOUBLE-BLIND, 3-ARM STUDY TO INVESTIGATE NIRMATRELVIR/RITONAVIR IN NONHOSPITALIZED PARTICIPANTS AT LEAST 12 YEARS OF AGE WITH SYMPTOMATIC COVID-19 WHO ARE IMMUNOCOMPROMISED
Actual Study Start Date : August 3, 2022
Actual Primary Completion Date : July 17, 2023
Actual Study Completion Date : November 13, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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
 Drug: Nirmatrelvir
Participants will receive 2 tablets of nirmatrelvir every 12 hours

Drug: Ritonavir
Participants will receive 1 capsule of ritonavir every 12 hours

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.

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.
Experimental: 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
 Drug: Nirmatrelvir
Participants will receive 2 tablets of nirmatrelvir every 12 hours

Drug: Ritonavir
Participants will receive 1 capsule of ritonavir every 12 hours

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.

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.
Experimental: Nirmatrelvir plus ritonavir for 15 days
Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 15 days.
 Drug: Nirmatrelvir
Participants will receive 2 tablets of nirmatrelvir every 12 hours

Drug: Ritonavir
Participants will receive 1 capsule of ritonavir every 12 hours


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of participants with sustained nasopharyngeal swab SARS-CoV-2 ribonucleic acid (RNA) <lower limit of quantitation (LLOQ) (defined as <2.0 log10 copies/mL). [ Time Frame: From Day 15 through Day 44 ]
    To describe the effect of nirmatrelvir/ritonavir on viral RNA levels in nasopharyngeal swabs over time for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.


Secondary Outcome Measures :
  1. Time to first nasopharyngeal swab SARS-CoV-2 RNA<LLOQ (<2.0 log10 copies/mL) for participants with nasopharyngeal swab SARS-CoV-2 RNA ≥LLOQ at baseline. [ Time Frame: Day 1 through Week 24 ]
    To describe the effect of nirmatrelvir/ritonavir treatment duration on the rate of sustained virologic clearance in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  2. Time to sustained nasopharyngeal swab SARS-CoV-2 RNA <LLOQ (<2.0 log10 copies/mL) for participants with nasopharyngeal swab SARS-CoV-2 RNA ≥LLOQ at baseline. [ Time Frame: Day 1 through Day 44 ]
    To describe the effect of nirmatrelvir/ritonavir treatment duration on the rate of sustained virologic clearance in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  3. Proportion of participants with SARS-CoV-2 RNA <LLOQ in plasma over time. [ Time Frame: Day 1 through Week 24 ]
    To describe the effect of nirmatrelvir/ritonavir on viral clearance for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  4. Proportion of participants with SARS-CoV-2 RNA level in nasopharyngeal swabs <2.0 log10 copies/mL at each study visit. [ Time Frame: Day 1 through Day 44 ]
    To describe the effect of nirmatrelvir/ritonavir on viral clearance for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  5. Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal swabs and in plasma over time. [ Time Frame: Day 1 through Week 24 ]
    To describe the effect of nirmatrelvir/ritonavir on viral clearance for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  6. Rebound in SARS-CoV-2 RNA level in nasopharyngeal swabs at follow up, defined as a half (0.5) log10 copies/mL increase or greater in SARS-CoV-2 RNA level, with a follow-up viral RNA level ≥2.5 log10 copies/mL [ Time Frame: End of treatment through Day 44 ]
    To describe the effect of nirmatrelvir/ritonavir on viral clearance for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  7. Incidence of treatment emergent adverse events. [ Time Frame: Day 1 through Week 24 ]
    To describe the safety and tolerability of nirmatrelvir/ritonavir for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  8. Incidence of serious adverse events and adverse events leading to discontinuations. [ Time Frame: Day 1 through Week 24 ]
    To describe the safety and tolerability of nirmatrelvir/ritonavir for the treatment of COVID-19 in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  9. Proportion of participants with COVID-19-related hospitalization >24 hours, or death from any cause. [ Time Frame: Day 1 through Day 28 ]
    To describe the effect of nirmatrelvir/ritonavir on hospitalization and all-cause mortality in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  10. Proportion of participants with death (all cause). [ Time Frame: Day 1 through Week 24 ]
    To describe the effect of nirmatrelvir/ritonavir on hospitalization and all-cause mortality in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  11. Proportion of participants with COVID-19-related hospitalization of any duration. [ Time Frame: Day 1 through Week 24 ]
    To describe COVID-19 related healthcare resource utilization in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised and treated with nirmatrelvir/ritonavir.

  12. Proportion of participants with COVID-19-related intensive care unit (ICU) admission of any duration. [ Time Frame: Day 1 through Week 24 ]
    To describe COVID-19 related healthcare resource utilization in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised and treated with nirmatrelvir/ritonavir.

  13. Proportion of participants requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation. [ Time Frame: Day 1 through Week 24 ]
    To describe COVID-19 related healthcare resource utilization in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised and treated with nirmatrelvir/ritonavir.

  14. Number of days in hospital and ICU stay in participants with COVID-19-related hospitalization. [ Time Frame: Day 1 through Week 24 ]
    To describe COVID-19 related healthcare resource utilization in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised and treated with nirmatrelvir/ritonavir.

  15. Plasma concentration of nirmatrelvir [ Time Frame: Day 1, Day 5, Day 10, and Day 15 ]
  16. Plasma concentration of ritonavir [ Time Frame: Day 1, Day 5, Day 10, and Day 15 ]
  17. Number of COVID-19-related medical visits through Day 44 and through Week 24. [ Time Frame: Day 1 through Day 44 and Week 24 ]
    To describe COVID-19 related healthcare resource utilization in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised and treated with nirmatrelvir/ritonavir.

  18. Duration of each targeted COVID-19 signs/symptoms. [ Time Frame: Day 1 through Day 44 ]
    To evaluate nirmatrelvir/ritonavir for the duration and severity of signs and symptoms in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.

  19. Proportion of participants with severe signs/symptoms attributed to COVID-19. [ Time Frame: Day 1 through Day 44 ]
    To evaluate nirmatrelvir/ritonavir for the duration and severity of signs and symptoms in nonhospitalized symptomatic participants ≥12 years of age with COVID-19 who are immunocompromised.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (applicable for both the main population and population with rebound):

  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05438602


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05438602    
Other Study ID Numbers: C4671034
2022-001362-35 ( EudraCT Number )
First Posted: June 30, 2022    Key Record Dates
Last Update Posted: January 25, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Paxlovid
Nirmatrelvir
Immunocompromised
Additional relevant MeSH terms:
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COVID-19
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Ritonavir
 Nirmatrelvir
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors