ImPROving Quality of LIFe in the Long COVID Patient

NCT05823896 | Completed Phase 2 FDA Drug

• 2 other identifiers: KI-PROLIFIC-20232022-003855-32
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the efficacy of orally administered nirmatrelvir/ritonavir compared with placebo/ritonavir to improve quality of life in non-hospitalized adult participants suffering from post-acute COVID-19 syndrome.

Conditions

Post-COVID-19 Syndrome; Long COVID; Long Covid19; COVID-19; POTS - Postural Orthostatic Tachycardia Syndrome; Post COVID-19 Condition; Post-COVID Syndrome; Post COVID-19 Condition, Unspecified; Postinfectious Inflammation; Postinfectious Disorder

Outcome Measures

Primary Outcomes (1)

• Change from baseline in quality of life over time

  The effect of oral administration of nirmatrelvir/ritonavir on quality of life measured as change from baseline using the EQ-5D-5L VAS scale.

  Baseline and day 16

Secondary Outcomes (16)

• Change from baseline in quality of life over time

  Baseline and days 45 and 90

• Change from baseline in hemodynamic response over time

  Baseline and days 45 and 90

• Change from baseline in dysautonomia over time

  Baseline and days 45 and 90

• Change from baseline in fever in patients with POTS over time

  Baseline and days 45 and 90

• Change from baseline in endothelial function over time

  Baseline and day 45

Other Outcomes (3)

• Change from baseline in relationships between genotypes and immune function over time

  At baseline and day 16

• Change from baseline in immune cell function over time

  At baseline and day 16

• Change from baseline in persistence of SARS-CoV-2 virus over time

  At baseline and day 16

Study Arms (2)

Nirmatrelvir/ritonavir

ACTIVE COMPARATOR

Oral nirmatrelvir/ritonavir (Paxlovid) 300/100 mg twice daily for 15 days

Drug: Nirmatrelvir/ritonavir

Placebo/ritonavir

PLACEBO COMPARATOR

Oral placebo/ritonavir 100 mg twice daily for 15 days

Drug: Placebo/ritonavir

Interventions

Nirmatrelvir/ritonavir DRUG

300/100 mg tablet twice daily (q12h) administered orally for 15 days

Also known as: Paxlovid

Nirmatrelvir/ritonavir

Placebo/ritonavir DRUG

100mg tablet twice daily (q12h) administered orally for 15 days

Also known as: Placebo

Placebo/ritonavir

Eligibility Criteria

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

You may qualify if:

• The subject has given written consent to participate in the study.
• ≥18 years of age at the time of the Screening Visit.
• Post-acute COVID-19 syndrome (PACS) according to the WHO definition.
• EQ-5D-5L VAS ≤ 50
• All fertile participants must agree to use a highly effective method of contraception for the duration of the study and 28 days after last intake of the IMP.

You may not qualify if:

• Other non-related conditions with PACS like symptoms.
• Renal function eGFR eGFRCysC \< 60 mL/min/1.73 m2.
• Not able to comply with the study protocol.
• Previous Paxlovid treatment.
• Pregnancy or breastfeeding.
• Drug-drug interaction with ongoing treatment, including concomitant use of any medications or substances that are strong inducers of CYP3A4 within 28 days prior to first dose of nirmatrelvir/ritonavir and during study treatment.
• Participants who are planning or considering vaccination (including boosters) through Study Day 45.
• Active COVID-19 infection as verified by SARS CoV-2 positive antigen test.
• Self-reported medical conditions, including:
• Type 1 or Type 2 diabetes mellitus.
• Chronic kidney disease.
• Neurodevelopmental disorders (e.g., cerebral palsy, Down's syndrome) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes and severe congenital anomalies).
• Active cancer other than localized skin cancer, including those requiring treatment including palliative treatment), as long as the treatment is not among the prohibited medications that must be administered/continued during the trial period.
• Immunosuppressive disease (e.g., bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications:
• i. Has received corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days within 30 days prior to study entry.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator
• Pfizer: collaborator

Study Sites (1)

Karolinska Institutet

Stockholm, SE171 77, Sweden

Location

Related Publications (9)

• Caruso D, Guido G, Zerunian M, Polidori T, Lucertini E, Pucciarelli F, Polici M, Rucci C, Bracci B, Nicolai M, Cremona A, De Dominicis C, Laghi A. Post-Acute Sequelae of COVID-19 Pneumonia: Six-month Chest CT Follow-up. Radiology. 2021 Nov;301(2):E396-E405. doi: 10.1148/radiol.2021210834. Epub 2021 Jul 27.

  PMID: 34313468 BACKGROUND

• Han X, Fan Y, Alwalid O, Li N, Jia X, Yuan M, Li Y, Cao Y, Gu J, Wu H, Shi H. Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology. 2021 Apr;299(1):E177-E186. doi: 10.1148/radiol.2021203153. Epub 2021 Jan 26.

  PMID: 33497317 BACKGROUND

• Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.

  PMID: 34973396 BACKGROUND

• Goh D, Lim JCT, Fernaindez SB, Joseph CR, Edwards SG, Neo ZW, Lee JN, Caballero SG, Lau MC, Yeong JPS. Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID. Front Immunol. 2022 Sep 5;13:939989. doi: 10.3389/fimmu.2022.939989. eCollection 2022.

  PMID: 36131932 BACKGROUND

• Visvabharathy L, Orban ZS, Koralnik IJ. Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence. Front Med (Lausanne). 2022 Sep 23;9:1003103. doi: 10.3389/fmed.2022.1003103. eCollection 2022.

  PMID: 36213654 BACKGROUND

• Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, Baniecki M, Hendrick VM, Damle B, Simon-Campos A, Pypstra R, Rusnak JM; EPIC-HR Investigators. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397-1408. doi: 10.1056/NEJMoa2118542. Epub 2022 Feb 16.

  PMID: 35172054 BACKGROUND

• Toussi SS, Neutel JM, Navarro J, Preston RA, Shi H, Kavetska O, LaBadie RR, Binks M, Chan PLS, Demers N, Corrigan B, Damle B. Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID-19, in Subjects With Renal Impairment. Clin Pharmacol Ther. 2022 Oct;112(4):892-900. doi: 10.1002/cpt.2688. Epub 2022 Jul 5.

  PMID: 35712797 BACKGROUND

• Sundaram A, Vaughan B, Kost K, Bankole A, Finer L, Singh S, Trussell J. Contraceptive Failure in the United States: Estimates from the 2006-2010 National Survey of Family Growth. Perspect Sex Reprod Health. 2017 Mar;49(1):7-16. doi: 10.1363/psrh.12017. Epub 2017 Feb 28.

  PMID: 28245088 BACKGROUND

• Swank Z, Senussi Y, Manickas-Hill Z, Yu XG, Li JZ, Alter G, Walt DR. Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. Clin Infect Dis. 2023 Feb 8;76(3):e487-e490. doi: 10.1093/cid/ciac722.

  PMID: 36052466 BACKGROUND

Related Links

• Recommendations related to contraception and pregnancy testing in clinical trials
• European Medicines Agency Assessment Report for Paxlovid
• Information related to Paxlovid
• Late breaking abstract 2021 ERS International Congress - Early follow-up of hospitalised and non-hospitalised patients with Covid-19 in a Swedish setting

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19; Postural Orthostatic Tachycardia Syndrome; Post-Infectious Disorders

Interventions

nirmatrelvir and ritonavir drug combination; Ritonavir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael Runold, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

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: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a phase II, interventional, randomized, parallel group, double-blind, placebo-controlled, single-center study of nirmatrelvir/ritonavir (300/100 mg) or placebo/ritonavir (100mg), administered orally twice daily for 15 days in non-hospitalized patients with post- COVID conditions.

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: April 21, 2023
• Study Start: May 1, 2023
• Primary Completion: November 28, 2024
• Study Completion: November 28, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)