A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir

• ClinicalTrials.gov Identifier: NCT05567952
• Recruitment Status: Completed
• First Posted: October 5, 2022
• Last Update Posted: March 26, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 3, 2022
• First Posted Date: October 5, 2022
• Last Update Posted Date: March 26, 2024
• Actual Study Start Date: October 19, 2022
• Actual Primary Completion Date: September 27, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2022)

The change in viral SARS-CoV-2 RNA level as measured in nasopharyngeal (NP) swabs [ Time Frame: Baseline to Day 5 ]

To compare the effect of nirmatrelvir/ritonavir to placebo/ritonavir on viral RNA level in NP swabs in participants with mild-to-moderate COVID-19.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 3, 2022)

• Time to 2 consecutive negative rapid antigen test results obtained at least 24 hours apart through Day 28 [ Time Frame: Day 1 through Day 28 ]
  To compare the effect of nirmatrelvir/ritonavir to placebo/ritonavir on the duration of viral shedding.
• Time to sustained alleviation of all targeted signs and symptoms defined as the first of two consecutive days when symptoms scored moderate/severe at baseline are scored mild/absent and symptoms scored mild/absent at baseline are scored absent. [ Time Frame: Day 1 through Day 28 ]
  To compare the effect of nirmatrelvir/ritonavir to placebo/ritonavir on the duration and severity of signs and symptoms in participants with mild-to-moderate COVID-19.
• Incidence of treatment emergent adverse events. [ Time Frame: Day 1 through Week 24 ]
  To describe the safety and tolerability of nirmatrelvir/ritonavir in participants with mild-to-moderate COVID-19.
• Incidence of serious adverse events and adverse events leading to discontinuation. [ Time Frame: Day 1 through Week 24 ]
  To describe the safety and tolerability of nirmatrelvir/ritonavir in participants with mild-to-moderate COVID-19.

• 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 a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir
• Official Title: AN INTERVENTIONAL, EFFICACY AND SAFETY, PHASE 2, RANDOMIZED, DOUBLE-BLIND, 2-ARM STUDY TO INVESTIGATE A REPEAT 5-DAY COURSE OF NIRMATRELVIR/RITONAVIR COMPARED TO PLACEBO/RITONAVIR IN PARTICIPANTS AT LEAST 12 YEARS OF AGE WITH REBOUND OF COVID-19 SYMPTOMS AND RAPID ANTIGEN TEST POSITIVITY

Brief Summary

The purpose of this study is to learn about the safety and effects of nirmatrelvir/ritonavir for the potential treatment of COVID-19 rebound.

The study is seeking participants who:

• Have completed treatment with nirmatrelvir/ritonavir
• Have a rebound in COVID-19 symptoms
• Are SARS-CoV-2 (COVID-19) positive

All study medications will be taken 2 times a day by mouth for 5 days. The first dose of study medication is taken at the study clinic and the rest at home.

We will examine the experiences of people receiving the study medicines to those who do not. This will help us determine if the study medicines are safe and effective.

People taking part will be in this study for about 24 weeks. Enrolled participants will need to visit the study clinic at least 8 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.

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
  Interventions:

  • Drug: nirmatrelvir
  • Drug: ritonavir
• placebo plus ritonavir for 5 days
  placebo (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days
  Interventions:

  • Drug: ritonavir
  • Drug: placebo for nirmatrelvir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2023): 436
• Original Estimated Enrollment (submitted: October 3, 2022): 411
• Actual Study Completion Date: February 9, 2024
• Actual Primary Completion Date: September 27, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Documentation of nirmatrelvir/ritonavir treatment with patient-reported 100% compliance. Symptom alleviation or resolution in COVID-19 signs/symptoms followed by a worsening (rebound) of signs/symptoms after completing an initial 5-day course of nirmatrelvir/ritonavir
• Onset of rebound in COVID-19 symptoms within 2 weeks (14 days) after the completion of the initial 5-day course of nirmatrelvir/ritonavir.
• Onset of rebound in signs/symptoms attributable to COVID-19 within 48 hours prior to randomization and ≥1 sign/symptom attributable to COVID-19 present on the day of randomization.
• SARS-CoV-2 infection as determined by rapid antigen testing within 24 hours prior to randomization
• At least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19.

Exclusion Criteria:

• Current need for hospitalization, hospitalized for the COVID-19 infection or anticipated need for hospitalization within 24 hours after randomization
• History of severe chronic liver disease
• 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
• Immunocompromised.
• 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: Canada, Greece, Italy, Taiwan, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT05567952
• Other Study ID Numbers: C4671042; 2022-002827-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

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: March 2024