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

NCT04362137 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CINC424J12301INCB 18424-3682020-001662-11
• Study Type: interventional
• Target: 432
• Locations: 12 countries
• Sites: 61

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.

Conditions

Cytokine Storm (Covid-19)

Keywords

COVID-19 pneumonia; cytokine release syndrome; SARS-COV-2; ruxolitinib

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care

  Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure \[require mechanical ventilation\], or require intensive care unit \[ICU\] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis.

  Day 1 - Day 29

Secondary Outcomes (13)

• Clinical Status

  Baseline, Day 15, Day 29

• Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status

  Baseline, Day 15, Day 29

• Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status

  Baseline, Day 15, Day 29

• Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status

  Baseline, Day 15, Day 29

• Time to Improvement in Clinical Status

  29 days

Study Arms (2)

Ruxolitinib 5 mg

EXPERIMENTAL

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

Drug: Ruxolitinib

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ruxolitinib DRUG

Ruxolitinib 5 mg tablets

Also known as: INC424

Ruxolitinib 5 mg

Placebo DRUG

Matching-image placebo

Placebo

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:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Incyte Corporation: collaborator

Study Sites (61)

Novartis Investigative Site

Fullerton, California, 92835, United States

Location

Novartis Investigative Site

Aurora, Colorado, 80045, United States

Location

Novartis Investigative Site

Denver, Colorado, 80205, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30312, United States

Location

Novartis Investigative Site

Idaho Falls, Idaho, 83404, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109, United States

Location

Novartis Investigative Site

Newark, New Jersey, 07103, United States

Location

Novartis Investigative Site

The Bronx, New York, 10461, United States

Location

Novartis Investigative Site

Mesquite, Texas, 75149, United States

Location

Novartis Investigative Site

Seattle, Washington, 98104, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53705-3611, United States

Location

Novartis Investigative Site

C A B A, Buenos Aires, CP1405, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1426AAM, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1430BKC, Argentina

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 22640-000, Brazil

Location

Novartis Investigative Site

Blumenau, Santa Catarina, 89030101, Brazil

Location

Novartis Investigative Site

Barretos, São Paulo, 14784 400, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01327 001, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04502 001, Brazil

Location

Novartis Investigative Site

Sorocaba, São Paulo, Brazil

Location

Novartis Investigative Site

Rionegro, Antioquia, 054047, Colombia

Location

Novartis Investigative Site

Barranquilla, Atlántico, 080005, Colombia

Location

Novartis Investigative Site

Barranquilla, Colombia

Location

Novartis Investigative Site

Colombes, 92701, France

Location

Novartis Investigative Site

Eaubonne, 95600, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Nuremberg, 90419, Germany

Location

Novartis Investigative Site

Mexico City, Mexico City, 14050, Mexico

Location

Novartis Investigative Site

Mexico City, Mexico CP, 14080, Mexico

Location

Novartis Investigative Site

Estado de México, 52787, Mexico

Location

Novartis Investigative Site

San Isidro, Lima region, 27, Peru

Location

Novartis Investigative Site

San Miguel, Lima region, 32, Peru

Location

Novartis Investigative Site

Lima, 10, Peru

Location

Novartis Investigative Site

Lima, 1, Peru

Location

Novartis Investigative Site

Barnaul, 656045, Russia

Location

Novartis Investigative Site

Moscow, 111539, Russia

Location

Novartis Investigative Site

Moscow, 123056, Russia

Location

Novartis Investigative Site

Ryazan, 390039, Russia

Location

Novartis Investigative Site

S-Petersburg, 194354, Russia

Location

Novartis Investigative Site

Saint Petersburg, 193312, Russia

Location

Novartis Investigative Site

Saint Petersburg, 194044, Russia

Location

Novartis Investigative Site

Saint Petersburg, 199106, Russia

Location

Novartis Investigative Site

Sestroretsk, 197706, Russia

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28031, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Turkey (Türkiye)

Location

Novartis Investigative Site

Yenisehir/Izmir, 35110, Turkey (Türkiye)

Location

Novartis Investigative Site

Harrow, HA1 3UJ, United Kingdom

Location

Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Novartis Investigative Site

London, WC1E 6HX, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9PL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35368384 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Cytokine Release Syndrome; COVID-19

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 24, 2020
• Study Start: May 2, 2020
• Primary Completion: October 17, 2020
• Study Completion: October 17, 2020
• Last Updated: October 11, 2021
• Results First Posted: June 2, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

RU (9); BR (6); AR (3); PE (4); ES (5); FR (5); TU (4); GB (5); ME (3); US (11); DE (3); CO (3)