Clinical trial NCT05438602: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Paxlovid
Nirmatrelvir
Immunocompromised
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-06-30
Enrollment: 158
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Sustained Nasopharyngeal (NP) Swab Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) < Lower Limit of Quantitation (LLOQ) From Day 15 to Day 44
timeFrame: From Day 15 to Day 44
Secondary outcomes:
measure: Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline
timeFrame: Day 1 through Day 44
measure: Time to First Sustained NP Swab SARS-CoV-2 RNA < LLOQ for Participants Through Day 44 With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline
timeFrame: Day 1 through Day 44
measure: Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24
timeFrame: Baseline; Days 5, 10, 15, 21, 28, 35, and 44; Weeks 12 and 24
measure: Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44
timeFrame: Baseline; Days 5, 10, 15, 21, 28, 35 and 44
measure: Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44
timeFrame: Baseline; Days 5, 10, 15, 21, 28, 35 and 44
measure: Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44
timeFrame: Baseline; Days 5, 10, 15, 21, 28, 35 and 44
measure: Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up
timeFrame: Day 16 through Day 44
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation
timeFrame: Day 1 of dosing up to Week 24
measure: Percentage of Participants With COVID-19-Related Hospitalization >24 Hours (h) or Death Through Day 28
timeFrame: Day 1 through Day 28
measure: Percentage of Participants With Death Through Week 24
timeFrame: Day 1 through Week 24
measure: Percentage of Participants With COVID-19-Related Hospitalization Through Day 44 and Week 24
timeFrame: Day 1 through Day 44 and Day 1 through Week 24
measure: Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24
timeFrame: Day 1 through Day 44 and Day 1 through Week 24
measure: Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24
timeFrame: Day 1 through Day 44 and Day 1 through Week 24
measure: Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24
timeFrame: Day 1 through Day 44 and Day 1 through Week 24
measure: Mean Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24
timeFrame: Day 1 through Day 44 and Day 1 through Week 24
measure: Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44
timeFrame: Day 1 through Day 44
measure: Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44
timeFrame: Day 1 through Day 44
measure: Percentage of Participants With Any Severe Targeted Signs and Symptoms Attributed to COVID-19 Through Day 44
timeFrame: Day 1 through Day 44
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: CRS Outpatient Services UCSF
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Medical Center at Parnassus Heights
state: California
city: San Francisco
country: United States
facility: UCSf infectious disease Lab
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Doral
country: United States
facility: I.V.A.M. Clinical & Investigational Center
state: Florida
city: Hialeah
country: United States
facility: Qway Research LLC
state: Florida
city: Miami
country: United States
facility: Premium Medical Research Corp
state: Florida
city: Miami
country: United States
facility: Global Health Clinical Trials
state: Florida
city: Miami
country: United States
facility: I.V.A.M. Clinical & Investigational Center
state: Florida
city: Pompano Beach
country: United States
facility: NAPA Research
state: Florida
city: Tampa
country: United States
facility: Santos Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital-Georgia Clinical Research Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Bethesda
country: United States
facility: National Institute of Health
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Infectious Diseases Research
state: Michigan
city: Sterling Heights
country: United States
facility: Revival Research Institute
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Corpus Christi
country: United States
facility: South Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center - COVID Clinical Research Center
state: Washington
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital - Royal Park Campus
state: Victoria
city: Natal
country: Brazil
facility: Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCLIN/RN
state: RIO Grande DO Norte
city: Jau
country: Brazil
facility: CECIP - Centro de Estudos do Interior Paulista
state: SÃO Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SÃO Paulo
city: Rio de Janeiro
country: Brazil
facility: IBPClin - Instituto Brasil de Pesquisa Clínica
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Infectologia Evandro Chagas
city: Lom
country: Bulgaria
facility: Diagnostic Consultative Center - 1 Lom EOOD
state: Montana
city: Sofia
country: Bulgaria
facility: Military Medical Academy
state: Sofia (stolitsa)
city: Samokov
country: Bulgaria
facility: MHAT Samokov
state: Sofia
city: Haskovo
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD
city: Pleven
country: Bulgaria
facility: MHAT - Heart and Brain
city: Plovdiv
country: Bulgaria
facility: Medical Center Artmed
city: Plovdiv
country: Bulgaria
facility: MHAT Sveta Karidad EAD
city: Vancouver
country: Canada
facility: Vancouver Infectious Diseases Centre
state: British Columbia
city: Guelph
country: Canada
facility: Dawson Clinical Research
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: Dr. Anil K. Gupta Medicine Professional Corporation
state: Ontario
city: Winchester
country: Canada
facility: Winchester District Memorial Hospital
state: Ontario
city: Chicoutimi
country: Canada
facility: INTERMED Groupe Sante
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medicale lActuel
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc.
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Trois-Rivieres Inc.
state: Quebec
city: Nyiregyhaza
country: Hungary
facility: Medifarma 98 Kft
state: Szabolcs-szatmár-bereg
city: Budapest
country: Hungary
facility: Dél-Pesti Centrumkórház Országos Hematológiai és infektológiai intézet, Szent László telep
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo LEÓN
city: Mérida
country: Mexico
facility: EME RED Hospitalaria
state: Yucatán
city: Durango
country: Mexico
facility: Instituto de Investigaciones Clínicas para la Salud
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S.C.
city: Veracruz
country: Mexico
facility: Instituto Veracruzano en Investigación Clínica S.C.
city: Veracruz
country: Mexico
facility: FAICIC S. de R.L. de C.V.
city: Rimavska Sobota
country: Slovakia
facility: REUMEX s.r.o.
state: Banskobystricky KRAJ
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
state: Bratislavský KRAJ
city: Topolcany
country: Slovakia
facility: ALERGIA s.r.o.
state: Nitriansky KRAJ
city: Pruske
country: Slovakia
facility: MUDr. Viliam Cibik, PhD., s.r.o.
state: Trenčiansky KRAJ
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda
city: Bratislava
country: Slovakia
facility: Univerzitná nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda
city: Kosice
country: Slovakia
facility: ARTROMAC n. o.
city: Presov
country: Slovakia
facility: MEDIKOMP, s.r.o
city: Spisska Nova Ves
country: Slovakia
facility: Plucna ambulancia Hrebenar s.r.o.
city: Spisska Nova Ves
country: Slovakia
facility: Plucna ambulancia Hrebenar, s.r.o.
city: Svidnik
country: Slovakia
facility: SANARE spol.s.r.o.
city: Topolcany
country: Slovakia
facility: ALERGIA s.r.o.
city: A Coruña
country: Spain
facility: CHUAC-Complejo Hospitalario Universitario A Coruña
state: A Coruña [LA Coruña]
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [cataluña]
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalunya [cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad DE
city: Vigo
country: Spain
facility: CHUVI- Hospital Alvaro Cunqueiro
state: Pontevedra [pontevedra]
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Valencia
country: Spain
facility: Hospital Clinico Universitario Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: