Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm

NCT ID: NCT04362137

Last Updated: 2021-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 432 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-02
• Study Completion Date: 2020-10-17

Brief Summary

This was a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 disease.

Detailed Description

This was a Phase III, multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of ruxolitinib in patients aged ≥12 years with COVID-19 disease. The study enrolled patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria were randomized in a 2:1 ratio to either oral ruxolitinib 5 mg twice daily + SoC or oral matching-image placebo + SoC for a total of 14 days. An additional 14 days of study drug could be given if in the opinion of the investigator the patient's clinical signs and symptoms did not improve, or worsen, and the potential benefit outweighed the potential risk.

The study included:

• Screening period of 0-2 days.
• Study period of 29 days (treatment of 14 days with possible extension of treatment to 28 days).

The primary objective was to evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29.

Conditions

Cytokine Storm (Covid-19)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ruxolitinib 5 mg

Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Ruxolitinib 5 mg tablets

Placebo

Matching-image placebo for 14 days with possible extension of treatment to 28 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching-image placebo

Interventions

Ruxolitinib

Ruxolitinib 5 mg tablets

Intervention Type: DRUG

Placebo

Matching-image placebo

Intervention Type: DRUG

Other Intervention Names

INC424

Eligibility Criteria

Inclusion Criteria

Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed.

Male and female patients aged ≥ 12 years (or ≥ the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals).

Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization.

Patients currently hospitalized or will be hospitalized prior to randomization.

Patients, who meet at least one of the below criteria:

• Pulmonary infiltrates (chest X ray or chest CT scan);
• Respiratory frequency ≥ 30/min;
• Requiring supplemental oxygen;
• Oxygen saturation ≤ 94% on room air;
• Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m).

Exclusion Criteria

History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.

Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 μmol/L), or have estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation.

Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).

Currently intubated or intubated between screening and randomization. In intensive care unit (ICU) at time of randomization. Intubated or in ICU for COVID-19 disease prior to screening. Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra).

Unable to ingest tablets at randomization. Pregnant or nursing (lactating) women

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Fullerton, California, United States

Novartis Investigative Site

Aurora, Colorado, United States

Novartis Investigative Site

Denver, Colorado, United States

Novartis Investigative Site

Atlanta, Georgia, United States

Novartis Investigative Site

Idaho Falls, Idaho, United States

Novartis Investigative Site

Ann Arbor, Michigan, United States

Novartis Investigative Site

Newark, New Jersey, United States

Novartis Investigative Site

The Bronx, New York, United States

Novartis Investigative Site

Mesquite, Texas, United States

Novartis Investigative Site

Seattle, Washington, United States

Novartis Investigative Site

Madison, Wisconsin, United States

Novartis Investigative Site

C A B A, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, Brazil

Novartis Investigative Site

Blumenau, Santa Catarina, Brazil

Novartis Investigative Site

Barretos, São Paulo, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Sorocaba, São Paulo, Brazil

Novartis Investigative Site

Rionegro, Antioquia, Colombia

Novartis Investigative Site

Barranquilla, Atlántico, Colombia

Novartis Investigative Site

Barranquilla, , Colombia

Novartis Investigative Site

Colombes, , France

Novartis Investigative Site

Eaubonne, , France

Novartis Investigative Site

Nantes, , France

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Pierre-Bénite, , France

Novartis Investigative Site

Lübeck, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Nuremberg, , Germany

Novartis Investigative Site

Mexico City, Mexico City, Mexico

Novartis Investigative Site

Mexico City, Mexico CP, Mexico

Novartis Investigative Site

Estado de México, , Mexico

Novartis Investigative Site

San Isidro, Lima region, Peru

Novartis Investigative Site

San Miguel, Lima region, Peru

Novartis Investigative Site

Lima, , Peru

Novartis Investigative Site

Lima, , Peru

Novartis Investigative Site

Barnaul, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Ryazan, , Russia

Novartis Investigative Site

S-Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Sestroretsk, , Russia

Novartis Investigative Site

Salamanca, Castille and León, Spain

Novartis Investigative Site

Badalona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Istanbul, TUR, Turkey (Türkiye)

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Novartis Investigative Site

Yenisehir/Izmir, , Turkey (Türkiye)

Novartis Investigative Site

Harrow, , United Kingdom

Novartis Investigative Site

Leeds, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Manchester, , United Kingdom

Countries

United States; Argentina; Brazil; Colombia; France; Germany; Mexico; Peru; Russia; Spain; Turkey (Türkiye); United Kingdom

References

Han MK, Antila M, Ficker JH, Gordeev I, Guerreros A, Bernus AL, Roquilly A, Sifuentes-Osornio J, Tabak F, Teijeiro R, Bandelli L, Bonagura DS, Shu X, Felser JM, Knorr B, Cao W, Langmuir P, Lehmann T, Levine M, Savic S. Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Rheumatol. 2022 May;4(5):e351-e361. doi: 10.1016/S2665-9913(22)00044-3. Epub 2022 Mar 29.

Reference Type: DERIVED

PMID: 35368384 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=942

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

INCB 18424-368

Identifier Type: OTHER

Identifier Source: secondary_id

2020-001662-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CINC424J12301

Identifier Type: -

Identifier Source: org_study_id