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

Pfizer158 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Interventions

NirmatrelvirDRUG

Participants will receive 2 tablets of nirmatrelvir every 12 hours

RitonavirDRUG

Participants will receive 1 capsule of ritonavir every 12 hours

Placebo for nirmatrelvirDRUG

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 ritonavirDRUG

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.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (84)

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

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

I.V.A.M. Clinical & Investigational Center

Doral, Florida, United States

Outcomes

Primary Outcomes

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

NP swab was collected by healthcare professional (HCP) from participants and were sent to the central laboratory for viral RNA level testing real-time reverse transcriptase-polymerase chain reaction(RT-PCR). Sustained was defined as NP swab SARS-CoV-2 RNA level not \>=2.0 log10 per milliliter (copies/mL) at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA level \<LLOQ (\<2.0 log10 copies/mL).

Time frame: From Day 15 to Day 44

Secondary Outcomes

Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline

An NP swab was collected by HCP from participants and were sent to the central laboratory for viral RNA level testing RT-PCR. The LLOQ is \<2.0 log10 copies/mL. Kaplan-Meier method was used for analysis. Time (days) to first NP swab SARS-CoV-2 RNA\<LLOQ (event) was calculated as (First Event Date) - (First Dose Date) +1.

Time frame: Day 1 through Day 44

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

An NP swab was collected by HCP from participants and were sent to the central laboratory for viral RNA level testing RT-PCR. Sustained was defined as NP swab SARS-CoV-2 RNA level not \>=2.0 log10 copies/mL at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA level \< LLOQ. The LLOQ is \<2.0 log10 copies/mL. Time (days) to first sustained NP swab SARS-CoV-2 RNA\<LLOQ (event) was calculated as (First Event Date) - (First Dose Date) +1.

Time frame: Day 1 through Day 44

Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24

A 6-mL blood sample was collected for adult and pediatric participants and was analyzed to measure SARS-CoV-2 RNA \<LLOQ in Plasma by RT-PCR. The LLOQ is \<2.0 log10 copies/mL.

Time frame: Baseline; Days 5, 10, 15, 21, 28, 35, and 44; Weeks 12 and 24

Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44

An NP swab was collected by HCP from adult and pediatric participants and were sent to the central laboratory for viral RNA level testing RT-PCR. The LLOQ is \<2.0 log10 copies/mL.

Time frame: Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44

An NP swab was collected by HCP from adult and pediatric participants and were sent to the central laboratory for viral RNA level testing RT-PCR.

Time frame: Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44

A 6-mL blood sample was collected for adult and pediatric participants and was analyzed to measure SARS-CoV-2 RNA by RT-PCR.

Time frame: Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up

Rebound in SARS-CoV-2 RNA level in NP swabs at follow up (ie, any study visit after end of treatment through Day 44) was defined as a half (0.5) log10 copies/mL increase or greater in SARS-CoV-2 RNA level relative to end of treatment SARS-CoV-2 RNA level based on treatment regimen, with a follow-up viral RNA level \>= 2.5 log10 copies/mL.

Time frame: Day 16 through Day 44

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation

An adverse event (AE) was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect.

Time frame: Day 1 of dosing up to Week 24

Percentage of Participants With COVID-19-Related Hospitalization >24 Hours (h) or Death Through Day 28

Hospitalization \>24 h is defined as \>24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. This included specialized acute medical care unit within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution.

Time frame: Day 1 through Day 28

Percentage of Participants With Death Through Week 24

Death due to any cause through week 24 was considered. Kaplan-Meier method was used for evaluation.

Time frame: Day 1 through Week 24

Percentage of Participants With COVID-19-Related Hospitalization Through Day 44 and Week 24

COVID-19 related hospitalization is defined as \>24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. This included specialized acute medical care unit within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution.