Phase 2
Completed N=157
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
Source: ClinicalTrials.gov NCT05438602 ↗Enrolled (actual)
157
Serious AEs
6.4%
Results posted
Sep 2024
Primary outcomePrimary: 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 — 61.54; 70.83; 66.00 Percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
61.54; 70.83; 66.00 | — |
| SECONDARY Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline |
9.500; 11.000; 9.000 | — |
| SECONDARY 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 |
15.000; 11.000; 10.000 | — |
| SECONDARY Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 |
98.08; 97.92; 92.00; 90.38; 93.75; 92.00 | — |
| SECONDARY Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 |
5.77; 8.33; 4.00; 38.46; 29.17; 38.00 | — |
| SECONDARY Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 |
-3.449; -3.621; -3.746; -4.167; -4.931; -5.002 | — |
| SECONDARY Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 |
-1.457; -1.360; -1.528; -1.487; -1.700; -1.880 | — |
| SECONDARY Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up |
9; 1; 1 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation |
28; 34; 31; 5; 1; 4 | — |
| SECONDARY Percentage of Participants With COVID-19-Related Hospitalization >24 Hours (h) or Death Through Day 28 |
3.846; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Death Through Week 24 |
1.923; 0; 0 | — |
| SECONDARY Percentage of Participants With COVID-19-Related Hospitalization Through Day 44 and Week 24 |
3.846; 0; 0; 3.846; 0; 0 | — |
| SECONDARY Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24 |
1.923; 0; 0; 1.923; 0; 0 | — |
| SECONDARY Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24 |
0.635; 0.000; 0.000; 0.635; 0.000; 0.000 | — |
| SECONDARY Mean Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24 |
0.115; 0.000; 0.000; 0.115; 0.000; 0.020 | — |
| SECONDARY Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 |
6.000; 9.000; 9.000; 6.000; 9.000; 6.000 | — |
| SECONDARY Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 |
14.500; 11.000; 10.000; 9.000; 9.500; 12.000 | — |
| SECONDARY Percentage of Participants With Any Severe Targeted Signs and Symptoms Attributed to COVID-19 Through Day 44 |
28.85; 31.25; 38.00 | — |
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
Data sourced from ClinicalTrials.gov (NCT05438602). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.