Clinical trial NCT04362137: Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cytokine Storm (Covid-19)
Keywords: COVID-19 pneumonia
cytokine release syndrome
SARS-COV-2
ruxolitinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Incyte Corporation
First posted: 2020-04-24
Enrollment: 432
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care
timeFrame: Day 1 - Day 29
Secondary outcomes:
measure: Clinical Status
timeFrame: Baseline, Day 15, Day 29
measure: Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status
timeFrame: Baseline, Day 15, Day 29
measure: Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status
timeFrame: Baseline, Day 15, Day 29
measure: Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status
timeFrame: Baseline, Day 15, Day 29
measure: Time to Improvement in Clinical Status
timeFrame: 29 days
measure: Mean Change From Baseline in the Clinical Status
timeFrame: Baseline, Day 15, Day 29
measure: Mortality Rate
timeFrame: Day 15, Day 29
measure: Proportion of Patients Requiring Mechanical Ventilation
timeFrame: Day 1 - Day 29
measure: Duration of Hospitalization
timeFrame: 29 days
measure: Time to Hospital Discharge or to a NEWS2 Score of ≤2
timeFrame: 29 days
measure: Change From Baseline in NEWS2 Score
timeFrame: Baseline, Days 3, 5, 8, 11, 15, and 29
measure: Change From Baseline in SpO2/FiO2 Ratio
timeFrame: Baseline, Day 15, Day 29
measure: Proportion of Patients With no Oxygen Therapy
timeFrame: Day 15, Day 29
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Novartis Investigative Site
state: California
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Idaho Falls
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Newark
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Bronx
country: United States
facility: Novartis Investigative Site
state: New York
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: C A B A
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Blumenau
country: Brazil
facility: Novartis Investigative Site
state: Santa Catarina
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sorocaba
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Rionegro
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Colombes Cedex
country: France
facility: Novartis Investigative Site
city: Eaubonne
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Lubeck
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Nuernberg
country: Germany
facility: Novartis Investigative Site
city: México
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Mexico CP
city: Estado de Mexico
country: Mexico
facility: Novartis Investigative Site
city: San Isidro
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Miguel
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: S-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sestroretsk
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluna
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Yenisehir/Izmir
country: Turkey
facility: Novartis Investigative Site
city: Harrow
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.