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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05438602
• Other study ID #: C4671034
• Secondary ID: 2022-001362-35
• Status: Completed
• Phase: Phase 2
• Start date: August 3, 2022
• Est. completion date: November 13, 2023

Study information

• Verified date: January 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: November 13, 2023
• Est. primary completion date: July 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Nirmatrelvir
Participants will receive 2 tablets of nirmatrelvir every 12 hours
• Ritonavir
Participants will receive 1 capsule of ritonavir every 12 hours
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital - Royal Park Campus	Parkville	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Brazil	CECIP - Centro de Estudos do Interior Paulista	Jau	SÃO Paulo
Brazil	Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCLIN/RN	Natal	RIO Grande DO Norte
Brazil	IBPClin - Instituto Brasil de Pesquisa Clínica	Rio de Janeiro
Brazil	Instituto Nacional de Infectologia Evandro Chagas	Rio de Janeiro
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	SÃO Paulo
Bulgaria	Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD	Haskovo
Bulgaria	Diagnostic Consultative Center - 1 Lom EOOD	Lom	Montana
Bulgaria	MHAT - Heart and Brain	Pleven
Bulgaria	Medical Center Artmed	Plovdiv
Bulgaria	MHAT Sveta Karidad EAD	Plovdiv
Bulgaria	MHAT Samokov	Samokov	Sofia
Bulgaria	Military Medical Academy	Sofia	Sofia (stolitsa)
Canada	INTERMED Groupe Sante	Chicoutimi	Quebec
Canada	Dawson Clinical Research	Guelph	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Clinique Medicale lActuel	Montreal	Quebec
Canada	Diex Recherche Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Diex Recherche Trois-Rivieres Inc.	Sherbrooke	Quebec
Canada	Dr. Anil K. Gupta Medicine Professional Corporation	Toronto	Ontario
Canada	Vancouver Infectious Diseases Centre	Vancouver	British Columbia
Canada	Winchester District Memorial Hospital	Winchester	Ontario
Hungary	Dél-Pesti Centrumkórház Országos Hematológiai és infektológiai intézet, Szent László telep	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Medifarma 98 Kft	Nyiregyhaza	Szabolcs-szatmár-bereg
Mexico	Instituto de Investigaciones Clínicas para la Salud	Durango
Mexico	EME RED Hospitalaria	Mérida	Yucatán
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City	Distrito Federal
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEÓN
Mexico	Oaxaca Site Management Organization S.C.	Oaxaca
Mexico	FAICIC S. de R.L. de C.V.	Veracruz
Mexico	Instituto Veracruzano en Investigación Clínica S.C.	Veracruz
Slovakia	Narodny onkologicky ustav	Bratislava	Bratislavský KRAJ
Slovakia	Univerzitna nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda	Bratislava
Slovakia	Univerzitná nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda	Bratislava
Slovakia	ARTROMAC n. o.	Kosice
Slovakia	MEDIKOMP, s.r.o	Presov
Slovakia	MUDr. Viliam Cibik, PhD., s.r.o.	Pruske	Trenciansky KRAJ
Slovakia	REUMEX s.r.o.	Rimavska Sobota	Banskobystricky KRAJ
Slovakia	Plucna ambulancia Hrebenar s.r.o.	Spisska Nova Ves
Slovakia	Plucna ambulancia Hrebenar, s.r.o.	Spisska Nova Ves
Slovakia	SANARE spol.s.r.o.	Svidnik
Slovakia	ALERGIA s.r.o.	Topolcany
Slovakia	ALERGIA s.r.o.	Topolcany	Nitriansky KRAJ
Spain	CHUAC-Complejo Hospitalario Universitario A Coruña	A Coruña	A Coruña [LA Coruña]
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona [barcelona]
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya [cataluña]
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Catalunya [cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Clinico de Valencia	Valencia	Valenciana, Comunitat
Spain	Hospital Clinico Universitario Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	CHUVI- Hospital Alvaro Cunqueiro	Vigo	Pontevedra [pontevedra]
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital-Georgia Clinical Research Center	Atlanta	Georgia
United States	Emory University School of Medicine	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	National Institute of Health	Bethesda	Maryland
United States	South Texas Clinical Research	Corpus Christi	Texas
United States	Baylor University Medical Center	Dallas	Texas
United States	North Texas Infectious Diseases Consultants, P.A	Dallas	Texas
United States	I.V.A.M. Clinical & Investigational Center	Doral	Florida
United States	Texas Centers for Infectious Disease Associates	Fort Worth	Texas
United States	Qway Research LLC	Hialeah	Florida
United States	Global Health Clinical Trials	Miami	Florida
United States	I.V.A.M. Clinical & Investigational Center	Miami	Florida
United States	Premium Medical Research Corp	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NAPA Research	Pompano Beach	Florida
United States	Beaumont Infectious Diseases Research	Royal Oak	Michigan
United States	MediSearch Clinical Trials	Saint Joseph	Missouri
United States	CRS Outpatient Services UCSF	San Francisco	California
United States	UCSF Helen Diller Medical Center at Parnassus Heights	San Francisco	California
United States	UCSf infectious disease Lab	San Francisco	California
United States	Fred Hutchinson Cancer Center - COVID Clinical Research Center	Seattle	Washington
United States	Revival Research Institute	Sterling Heights	Michigan
United States	Santos Research Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Bulgaria,  Canada,  Hungary,  Mexico,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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.	From Day 15 through Day 44
Secondary	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.	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.	Day 1 through Week 24
Secondary	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.	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.	Day 1 through Day 44
Secondary	Proportion of participants with SARS-CoV-2 RNA <LLOQ in plasma over time.	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.	Day 1 through Week 24
Secondary	Proportion of participants with SARS-CoV-2 RNA level in nasopharyngeal swabs <2.0 log10 copies/mL at each study visit.	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.	Day 1 through Day 44
Secondary	Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal swabs and in plasma over time.	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.	Day 1 through Week 24
Secondary	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	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.	End of treatment through Day 44
Secondary	Incidence of treatment emergent adverse events.	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.	Day 1 through Week 24
Secondary	Incidence of serious adverse events and adverse events leading to discontinuations.	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.	Day 1 through Week 24
Secondary	Proportion of participants with COVID-19-related hospitalization >24 hours, or death from any cause.	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.	Day 1 through Day 28
Secondary	Proportion of participants with death (all cause).	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.	Day 1 through Week 24
Secondary	Proportion of participants with COVID-19-related hospitalization of any duration.	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.	Day 1 through Week 24
Secondary	Proportion of participants with COVID-19-related intensive care unit (ICU) admission of any duration.	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.	Day 1 through Week 24
Secondary	Proportion of participants requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation.	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.	Day 1 through Week 24
Secondary	Number of days in hospital and ICU stay in participants with COVID-19-related hospitalization.	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.	Day 1 through Week 24
Secondary	Plasma concentration of nirmatrelvir		Day 1, Day 5, Day 10, and Day 15
Secondary	Plasma concentration of ritonavir		Day 1, Day 5, Day 10, and Day 15
Secondary	Number of COVID-19-related medical visits through Day 44 and 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.	Day 1 through Day 44 and Week 24
Secondary	Duration of each targeted COVID-19 signs/symptoms.	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.	Day 1 through Day 44
Secondary	Proportion of participants with severe signs/symptoms attributed to COVID-19.	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.	Day 1 through Day 44

External Links

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