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

• ClinicalTrials.gov Identifier: NCT05438602
• Recruitment Status: Completed
• First Posted: June 30, 2022
• Last Update Posted: January 25, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 28, 2022
• First Posted Date: June 30, 2022
• Last Update Posted Date: January 25, 2024
• Actual Study Start Date: August 3, 2022
• Actual Primary Completion Date: July 17, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 16, 2022)

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.

Original Primary Outcome Measures (submitted: June 28, 2022)

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: End of active treatment period 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.

Current Secondary Outcome Measures (submitted: June 28, 2022)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Plasma concentration of nirmatrelvir [ Time Frame: Day 1, Day 5, Day 10, and Day 15 ]
• Plasma concentration of ritonavir [ Time Frame: Day 1, Day 5, Day 10, and Day 15 ]
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• 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.

Study Arms

• 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
  Interventions:

  • Drug: Nirmatrelvir
  • Drug: Ritonavir
  • Drug: Placebo for nirmatrelvir
  • Drug: Placebo for ritonavir
• 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
  Interventions:

  • Drug: Nirmatrelvir
  • Drug: Ritonavir
  • Drug: Placebo for nirmatrelvir
  • Drug: Placebo for ritonavir
• 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.
  Interventions:

  • Drug: Nirmatrelvir
  • Drug: Ritonavir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 24, 2024): 157
• Original Estimated Enrollment (submitted: June 28, 2022): 172
• Actual Study Completion Date: November 13, 2023
• Actual Primary Completion Date: July 17, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Bulgaria, Canada, Hungary, Mexico, Slovakia, Spain, United States

Administrative Information

• NCT Number: NCT05438602
• Other Study ID Numbers: C4671034; 2022-001362-35 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: January 2024