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Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID) (RUXCOVID)

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ClinicalTrials.gov Identifier: NCT04362137
Recruitment Status : Completed
First Posted : April 24, 2020
Last Update Posted : November 12, 2020
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 22, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date November 12, 2020
Actual Study Start Date  ICMJE May 2, 2020
Actual Primary Completion Date October 17, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
Proportion of patients who die, develop respiratory failure [require mechanical ventilation] or require intensive care unit (ICU) care [ Time Frame: 29 days ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • Clinical status [ Time Frame: Day 15, Day 29 ]
    Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
  • Percentage of patients with at least two-point improvement from baseline in clinical status [ Time Frame: Baseline, Day 15, Day 29 ]
    Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale.
  • Percentage of patients with at least one-point improvement from baseline in clinical status [ Time Frame: Baseline, Day 15, Day 29 ]
    Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale.
  • Percentage of patients with at least one-point deterioration from baseline in clinical status [ Time Frame: Baseline, Day 15, Day 29 ]
    Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale.
  • Time to improvement in clinical status [ Time Frame: 29 days ]
    Time to improvement from baseline category to one less severe category of the 9-point ordinal scale.
  • Mean change from baseline in the clinical status [ Time Frame: Baseline, Day 15, Day 29 ]
    Mean change from baseline in the 9-point ordinal scale.
  • Mortality rate [ Time Frame: Day 15, Day 29 ]
    Mortality rate at Day 15 and at Day 29
  • Proportion of patients requiring mechanical ventilation [ Time Frame: 29 days ]
    Proportion of patients requiring mechanical ventilation
  • Duration of hospitalization [ Time Frame: 29 days ]
    Duration of hospitalization
  • Time to discharge or to a NEWS2 score of ≤2 [ Time Frame: 29 days ]
    The time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).
  • Change from baseline in NEWS2 score [ Time Frame: Baseline, Days 3, 5, 8, 11, 15, and 29 ]
    The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).
  • Change from baseline in SpO2/FiO2 ratio. [ Time Frame: Baseline, Day 15, Day 29 ]
    Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio)
  • Proportion of patients with no oxygen therapy [ Time Frame: Day 15, Day 29 ]
    No oxygen therapy is required if oxygen saturation is ≥ 94% on room air.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)
Official Title  ICMJE Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)
Brief Summary This is 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 pneumonia.
Detailed Description

This is 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 associated cytokine storm. The study will enroll patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria will be 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 may be given, if in the opinion of the investigator, the patient's clinical signs and symptoms are not improved or worsen and the potential benefit outweighs the potential risk.

The study will include:

  • Screening period of 0-2 days.
  • Study period of 29 days (treatment of 14 days; an additional 14 days of study drug may be given, if in the opinion of the investigator, the patient's clinical signs and symptoms are not improved or worsen and the potential benefit outweighs the potential risk).

The primary objective is 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cytokine Storm (Covid-19)
Intervention  ICMJE
  • Drug: Ruxolitinib
    Ruxolitinib 5 mg tablets
    Other Name: INC424
  • Drug: Placebo
    Matching-image placebo
Study Arms  ICMJE
  • Experimental: Ruxolitinib 5 mg
    Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days
    Intervention: Drug: Ruxolitinib
  • Placebo Comparator: Placebo
    Matching-image placebo for 14 days with possible extension of treatment to 28 days
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 23, 2020)
432
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2020)
402
Actual Study Completion Date  ICMJE October 17, 2020
Actual Primary Completion Date October 17, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Colombia,   France,   Germany,   Mexico,   Peru,   Russian Federation,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries Canada,   Italy
 
Administrative Information
NCT Number  ICMJE NCT04362137
Other Study ID Numbers  ICMJE CINC424J12301
INCB 18424-368 ( Other Identifier: Incyte Study Code )
2020-001662-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Incyte Corporation
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP