A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People With Weakened Immune Systems or at Increased Risk for Poor Outcomes Who Are Hospitalized Due to Severe COVID-19

NCT05545319 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: C46710312022-002447-22
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 11

Brief Summary

A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People with Weakened Immune Systems or at Increased Risk for Poor Outcomes who are Hospitalized Due to Severe COVID-19

Conditions

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); Coronavirus Disease 2019 (COVID-19); Immunocompromised; Hospitalization; Child, Hospitalized

Keywords

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Ribonucleic acid (RNA) virus Infections; Lung Diseases; Respiratory Tract Diseases; Ritonavir; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms; Pharmacological Action; Anti-human immunodeficiency virus (HIV) Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Paxlovid; Nirmatrelvir

Outcome Measures

Primary Outcomes (1)

• Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal (NP) swabs

  Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.

  Day 1 through Day 5

Secondary Outcomes (6)

• Time to sustained clinical recovery.

  Day 1 through Day 30

• Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

  Day 1 through Day 30

• Proportion of participants with SARS-CoV-2 RNA <Lower Limit of Quantitation (<LLOQ) (defined as <2.0 log10 copies/mL) in NP swabs

  Day 1 through Day 15

• Proportion of participants with sustained NP swab SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL)

  Day 15 through Day 45

• Incidence of Treatment-Related Adverse Events (TEAEs)

  Day 1 through Day 45

Study Arms (2)

Nirmatrelvir/ritonavir

EXPERIMENTAL

Participants will receive nirmatrelvir/ ritonavir 300 mg/100 mg (or 150 mg/100 mg for participants with estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCrCl) ≥30 to \<60 mL/min) every 12 hours from Day 1 through Day 15

Drug: Nirmatrelvir; Drug: Ritonavir

Placebo/ritonavir

EXPERIMENTAL

Participants will receive placebo 0 mg/ritonavir 100 mg every 12 hours for 15 days.

Drug: Ritonavir; Drug: Placebo for nirmatrelvir

Interventions

Nirmatrelvir DRUG

Participants will receive 2 tablets of nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to \<60 mL/min) every 12 hours

Also known as: Paxlovid

Nirmatrelvir/ritonavir

Ritonavir DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

Also known as: Norvir

Nirmatrelvir/ritonavir; Placebo/ritonavir

Placebo for nirmatrelvir DRUG

Participants will receive 2 tablets of placebo for nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to \<60 mL/min) every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.

Placebo/ritonavir

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Meeting 1 of the 2 categories of COVID-19 risk:
• Category A: Immunocompromised
• Category B: Non-Immunocompromised, but with ≥2 risk factors
• Onset of signs/symptoms attributable to COVID-19 ≤10 days prior to the day of randomization for non-immunocompromised participants (Category B).
• Confirmed SARS-CoV-2 infection as determined by Reverse transcription polymerase chain reaction (RT-PCR) or acceptable test method performed by a health care provider in any specimen collected within 48 hours prior to randomization.
• Hospitalized for inpatient care for the treatment of clinical manifestations of severe COVID-19.
• Requirement for oxygen supplementation (via nasal cannula, mask, non-invasive ventilation \[NIV\] or high flow oxygen) to maintain SpO2 ≥94% at the time of Screening and Randomization.

You may not qualify if:

• Critical illness, defined by ≥1 of the following:
• Requirement for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at randomization, or likely to require intermittent mandatory ventilation (IMV) or ECMO within 12 hours of randomization .
• Multi-organ dysfunction/failure.
• Hemodynamically unstable, eg. septic shock, cardiac failure or requiring vasopressors.
• Participant not expected to survive 24 hours from time of randomization.
• History of severe chronic liver disease
• Receiving dialysis of any kind or severe renal impairment
• Use of nirmatrelvir/ritonavir as an outpatient to treat the current COVID-19 related illness ≤7 days of randomization

Sponsors & Collaborators

• Pfizer: lead

Study Sites (11)

Bassett Medical Center

Cooperstown, New York, 13326, United States

Location

Harlem Hospital Center

New York, New York, 10037, United States

Location

Multiprofile Hospital for Active Treatment - Sveti Nikolay Chudotvoretz

Lom, Montana, 3600, Bulgaria

Location

Multiprofile Hospital for Active Treatment Sv. Ivan Rilski - Kozloduy EOOD

Kozloduy, Vratsa, 3320, Bulgaria

Location

Multiprofile Hospital for Active Treatment - Haskovo AD

Haskovo, 6304, Bulgaria

Location

Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD

Haskovo, 6305, Bulgaria

Location

"Specialized Hospital for Active Treatment of Lung Diseases - Pernik" EOOD

Pernik, 2300, Bulgaria

Location

"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD

Pleven, 5800, Bulgaria

Location

MHAT - Heart and Brain

Pleven, 5804, Bulgaria

Location

"Multiprofile Hospital for Active Treatment - Medical Complex Sveti Ivan Rilski" EOOD

Plovdiv, 4003, Bulgaria

Location

UMHAT "Prof. Dr. Stoyan Kirkovich"AD

Stara Zagora, 6003, Bulgaria

Location

Related Links

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

MeSH Terms

Conditions

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Lung Diseases; Respiratory Tract Diseases

Interventions

nirmatrelvir; nirmatrelvir and ritonavir drug combination; Ritonavir

Condition Hierarchy (Ancestors)

RNA Virus Infections

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 19, 2022
• Study Start: December 13, 2022
• Primary Completion: September 21, 2023
• Study Completion: January 6, 2024
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

BU (9); US (2)