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
- Conditions
- COVID-19
- Interventions
- Registration Number
- NCT05438602
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 157
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nirmatrelvir plus ritonavir for 10 days Placebo for nirmatrelvir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 10 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 5 days Nirmatrelvir plus ritonavir for 5 days Placebo for nirmatrelvir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 10 days Nirmatrelvir plus ritonavir for 5 days Placebo for ritonavir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 10 days Nirmatrelvir plus ritonavir for 10 days Placebo for ritonavir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 10 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 5 days Nirmatrelvir plus ritonavir for 5 days Nirmatrelvir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 10 days Nirmatrelvir plus ritonavir for 5 days Ritonavir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 10 days Nirmatrelvir plus ritonavir for 10 days Ritonavir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 10 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 5 days Nirmatrelvir plus ritonavir for 10 days Nirmatrelvir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 10 days followed by placebo for nirmatrelvir (2 tablets) plus placebo for ritonavir (1 capsule) every 12 hours for 5 days Nirmatrelvir plus ritonavir for 15 days Nirmatrelvir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 15 days. Nirmatrelvir plus ritonavir for 15 days Ritonavir Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 15 days.
- Primary Outcome Measures
Name Time Method 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 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).
- Secondary Outcome Measures
Name Time Method Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline Day 1 through Day 44 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 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 Day 1 through Day 44 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.
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Baseline; Days 5, 10, 15, 21, 28, 35, and 44; Weeks 12 and 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.
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Baseline; 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. The LLOQ is \<2.0 log10 copies/mL.
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Baseline; 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.
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Baseline; 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.
Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up Day 16 through Day 44 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation Day 1 of dosing up to Week 24 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.
Percentage of Participants With COVID-19-Related Hospitalization >24 Hours (h) or Death Through Day 28 Day 1 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.
Percentage of Participants With COVID-19-Related Hospitalization Through Day 44 and Week 24 Day 1 through Day 44 and Day 1 through 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.
Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24 Day 1 through Day 44 and Day 1 through Week 24 Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24 Day 1 through Day 44 and Day 1 through Week 24 Invasive mechanical ventilation or ECMO were types of oxygen support received in hospital.
Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24 Day 1 through Day 44 and Day 1 through Week 24 Hospitalization \>24 hours 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.
Mean Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24 Day 1 through Day 44 and Day 1 through Week 24 Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Day 1 through Day 44 Symptoms alleviation through day44 of each targeted COVID-19 sign/symptom was defined as first time when each targeted symptom scored as moderate/severe at study entry are scored as mild or absent and a targeted symptom scored mild or absent at study entry are scored as absent.COVID-19 targeted signs/symptoms were muscle or body aches,shortness of breath(SOB)or difficulty breathing,chills or shivering, cough,diarrhea,feeling hot or feverish,headache,nausea,stuffy or runny nose,sense of smell,sense of taste,sore throat,low energy or tiredness, vomit.
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Day 1 through Day 44 Symptoms resolution through day 44 of each targeted COVID-19 sign/symptom was defined as the first time when each targeted symptom scored as mild, moderate or severe at study entry are scored as absent. COVID -19 targeted signs/symptoms were muscle or body aches, SOB or difficulty breathing, chills or shivering, cough, diarrhoea, feeling hot or feverish, headache, nausea, stuffy or runny nose, sense of smell, sense of taste, sore throat, low energy or tiredness, vomit.
Percentage of Participants With Any Severe Targeted Signs and Symptoms Attributed to COVID-19 Through Day 44 Day 1 through Day 44 COVID-19 targeted signs/symptoms were muscle or body aches, SOB or difficulty breathing, chills or shivering, cough, diarrhea, feeling hot or feverish, headache, nausea, stuffy or runny nose, sense of smell, sense of taste, sore throat, low energy or tiredness, vomit.
Percentage of Participants With Death Through Week 24 Day 1 through Week 24 Death due to any cause through week 24 was considered. Kaplan-Meier method was used for evaluation.
Trial Locations
- Locations (82)
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, District of Columbia, United States
I.V.A.M. Clinical & Investigational Center
🇺🇸Miami, Florida, United States
Qway Research LLC
🇺🇸Hialeah, Florida, United States
Premium Medical Research Corp
🇺🇸Miami, Florida, United States
Global Health Clinical Trials
🇺🇸Miami, Florida, United States
NAPA Research
🇺🇸Pompano Beach, Florida, United States
Santos Research Center
🇺🇸Tampa, Florida, United States
Scroll for more (72 remaining)CRS Outpatient Services UCSF🇺🇸San Francisco, California, United States