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History of Changes for Study: NCT04362137
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)
Latest version (submitted October 7, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 22, 2020 None (earliest Version on record)
2 May 5, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 May 20, 2020 Contacts/Locations and Study Status
4 May 22, 2020 Eligibility and Study Status
5 June 2, 2020 Conditions and Study Status
6 June 5, 2020 Study Status, Conditions and Contacts/Locations
7 June 16, 2020 Study Status and Contacts/Locations
8 June 25, 2020 Contacts/Locations and Study Status
9 July 3, 2020 Study Status and Contacts/Locations
10 July 13, 2020 Contacts/Locations and Study Status
11 July 28, 2020 Study Status and Contacts/Locations
12 August 24, 2020 Study Status and Contacts/Locations
13 September 1, 2020 Study Status and Contacts/Locations
14 September 14, 2020 Study Status and Contacts/Locations
15 October 5, 2020 Study Status and Contacts/Locations
16 October 16, 2020 Contacts/Locations and Study Status
17 October 23, 2020 Recruitment Status, Contacts/Locations, Study Status and Study Design
18 November 10, 2020 Recruitment Status and Study Status
19 April 15, 2021
Quality Control Review has not concluded Returned: April 20, 2021
Outcome Measures, Study Status, Study Description, Document Section, Eligibility and Study Identification
20 May 12, 2021
Quality Control Review has not concluded Returned: May 18, 2021
Outcome Measures, Study Status, Adverse Events, Participant Flow
21 May 28, 2021 Study Status, Adverse Events and Outcome Measures
22 October 7, 2021 Study Status and References
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Study NCT04362137
Submitted Date:  April 22, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: CINC424J12301
Brief Title: 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)
Official Title: 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)
Secondary IDs: INCB 18424-368 [Incyte Study Code]
2020-001662-11 [EudraCT Number]
Open or close this module Study Status
Record Verification: April 2020
Overall Status: Not yet recruiting
Study Start: April 30, 2020
Primary Completion: June 29, 2020 [Anticipated]
Study Completion: June 29, 2020 [Anticipated]
First Submitted: April 22, 2020
First Submitted that
Met QC Criteria:
April 22, 2020
First Posted: April 24, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
April 22, 2020
Last Update Posted: April 24, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators: Incyte Corporation
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.

Open or close this module Conditions
Conditions: COVID-19
Keywords: COVID-19 pneumonia
cytokine release syndrome
SARS-COV-2
ruxolitinib
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 402 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Ruxolitinib 5 mg
Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days
Drug: Ruxolitinib
Ruxolitinib 5 mg tablets
Other Names:
  • INC424
Placebo Comparator: Placebo
Matching-image placebo for 14 days with possible extension of treatment to 28 days
Drug: Placebo
Matching-image placebo
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
Secondary Outcome Measures:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Mortality rate
[ Time Frame: Day 15, Day 29 ]

Mortality rate at Day 15 and at Day 29
8. Proportion of patients requiring mechanical ventilation
[ Time Frame: 29 days ]

Proportion of patients requiring mechanical ventilation
9. Duration of hospitalization
[ Time Frame: 29 days ]

Duration of hospitalization
10. 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).

11. 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).
12. 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)
13. 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.
Open or close this module Eligibility
Minimum Age: 12 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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 with lung imaging showing pulmonary infiltrates (chest X-ray or CT scan) prior to randomization.

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

Respiratory frequency ≥ 30/min; Oxygen saturation ≤ 93% 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. 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.

Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: 1-888-669-6682
Email: novartis.email@novartis.com
Central Contact Backup: Novartis Pharmaceuticals
Telephone: +41613241111
Study Officials: Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes

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

Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services