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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05567952

Collaborator

(none)

411

Enrollment

Locations

Arms

13.3

Anticipated Duration (Months)

9.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: nirmatrelvir Drug: ritonavir Drug: placebo for nirmatrelvir	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

411 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, 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

Actual Study Start Date :

Oct 19, 2022

Anticipated Primary Completion Date :

Jul 10, 2023

Anticipated Study Completion Date :

Nov 28, 2023

Arms and Interventions

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	Drug: nirmatrelvir Participants will receive 2 tablets of nirmatrelvir every 12 hours Drug: ritonavir Participants will receive 1 capsule of ritonavir every 12 hours
Other: placebo plus ritonavir for 5 days placebo (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days	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.

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

Drug: nirmatrelvir

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Drug: ritonavir

Participants will receive 1 capsule of ritonavir every 12 hours

Other: placebo plus ritonavir for 5 days

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

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.

Outcome Measures

Primary Outcome Measures

The change in viral SARS-CoV-2 RNA level as measured in nasopharyngeal (NP) swabs [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.

Secondary Outcome Measures

Time to 2 consecutive negative rapid antigen test results obtained at least 24 hours apart through Day 28 [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. [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. [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. [Day 1 through Week 24]
To describe the safety and tolerability of nirmatrelvir/ritonavir in participants with mild-to-moderate COVID-19.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Institute for Liver Health dba Arizona Clinical Trials	Mesa	Arizona	United States	85210
2	Abby's Research institute	Phoenix	Arizona	United States	85031
3	Ark Clinical Research	Long Beach	California	United States	90806
4	CVS Health - 8876 - Long Beach	Long Beach	California	United States	90806
5	Carbon Health - North Hollywood - NoHo West	North Hollywood	California	United States	91606
6	CVS Health - Site 9715 Thousand Oaks	Thousand Oaks	California	United States	91361
7	Emerson Clinical Research Institute	Washington	District of Columbia	United States	20011
8	TrueBlue Clinical Research	Brandon	Florida	United States	33511
9	Herco Medical and Research Center Inc	Coral Gables	Florida	United States	33134
10	Unlimited Medical Research Group	Hialeah Gardens	Florida	United States	33018
11	Premium Medical Research Corp	Miami	Florida	United States	33126
12	Global Health Clinical Trials	Miami	Florida	United States	33135
13	USPA Advance Concept Medical Research Group	Miami	Florida	United States	33143
14	Reliant Medical Research	Miami	Florida	United States	33165
15	Innova Pharma Research	Miami	Florida	United States	33175
16	Entrust Clinical Research	Miami	Florida	United States	33176
17	Reed Medical Research	Miami	Florida	United States	33176
18	Omega Research Orlando	Orlando	Florida	United States	32808
19	NAPA Research	Pompano Beach	Florida	United States	33064
20	GCP, Global Clinical Professionals	Saint Petersburg	Florida	United States	33705
21	Asclepes Research Center - Spring Hill	Spring Hill	Florida	United States	34609
22	Santos Research Center	Tampa	Florida	United States	33615
23	Bingham Memorial Hospital	Blackfoot	Idaho	United States	83221
24	University of Chicago Medical Center	Chicago	Illinois	United States	60637
25	Centennial Medical Group	Elkridge	Maryland	United States	21075
26	Great Lakes Research Group, Inc.	Bay City	Michigan	United States	48706
27	Mercury Street Medical Group, PLLC	Butte	Montana	United States	59701
28	OnSite Clinical Solutions	Charlotte	North Carolina	United States	28208
29	Accellacare - Wilmington - 1917 Tradd Court	Wilmington	North Carolina	United States	28401
30	Accellacare - Wilmington	Wilmington	North Carolina	United States	28401
31	Willamette Valley Clinical Studies	Eugene	Oregon	United States	97404
32	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania	United States	15009
33	Headlands Research - Brownsville	Brownsville	Texas	United States	78526
34	Southwest Family Medicine Associates	Dallas	Texas	United States	75235
35	Next Innovative Clinical Research	Houston	Texas	United States	77021
36	Next Level Urgent Care	Houston	Texas	United States	77057
37	Accurate Clinical Research - Jones Road	Houston	Texas	United States	77065
38	Accurate Clinical Research - East Humble	Humble	Texas	United States	77338
39	Sun Research Institute	San Antonio	Texas	United States	78215
40	Eastside Research Associates	Redmond	Washington	United States	98052
41	Dawson Clinical Research	Guelph	Ontario	Canada	N1H 1B1
42	Hamilton Medical Research Group	Hamilton	Ontario	Canada	L8M 1K7
43	Winchester District Memorial Hospital	Winchester	Ontario	Canada	K0C 2K0
44	Taichung Veterans General Hospital	Taichung		Taiwan	407