Safety and Efficacy of Ruxolitinib for COVID-19

COVID-19 Clinical Trial

Official title:

Safety and Efficacy of Ruxolitinib for COVID-19

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04348071
• Other study ID #: 20-0869
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: July 2021
• Est. completion date: October 2021

Study information

• Verified date: March 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study plans to learn more about the effects of a medicine called ruxolitinib on the progression of COVID-19 (coronavirus disease of 2019), the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ruxolitinib is FDA-approved for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. This study intends to define the impact of ruxolitinib on the severity and progression of COVID-19. This drug might to lower the hyperinflammation caused by the virus, which would prevent damage to the lungs and possibly other organs. The study will recruit patients who have been diagnosed with COVID-19. The goal is to recruit 80 patients.

Description:

This is an adaptive Phase 2/3 clinical trial, with a focus on the assessment of safety in the first 20 participants (Phase 2), followed by a much broader assessment of efficacy, while continuing to monitor safety, in an additional 60 participants (Phase 3, total participants across Phase 2/3 n=80). Both phases are single arm, open label, and occur at a single site at the University of Colorado Hospital (UCH). Data from participants in this study will be compared with data from other COVID-19 patients not receiving ruxolitinib. Study participants will receive 10 mg twice daily of ruxolitinib for 14 days and will be followed for up to 29 days.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• Male or female aged 18 - 89 years at time of enrollment
• Hospitalized (or documented plan to hospitalize if patient is in the emergency department) with symptoms suggestive of COVID-19
• lllness of any duration that meets each of the following:
• Evidence of pneumonia, including radiographic infiltrates by imaging (chest x-ray, CT scan, etc.) or clinical assessment (rales/crackles on exam)
• Requires supportive care, including non-invasive supplemental oxygen
• Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay within 7 days of enrollment
• Understands and agrees to comply with planned study procedures
• Provides informed consent signed by study patient or legally acceptable representative

Exclusion Criteria:

• Absolute platelet counts are less than 75 x 10^9/L
• Absolute neutrophil count is less than 0.5 x 10^9/L
• Hemoglobin is less than 8 g/dL
• Severe renal impairment defined by serum creatinine greater than 2 mg/dL or CrCl less than 30 mL/min
• Treatment with other JAK inhibitors, strong CYP3A4 inhibitors, biologic disease-modifying anti-rheumatic drugs (DMARDs, including anti-IL-6 or anti-IL-6R antibodies), or potent immunosuppressants such as azathioprine and cyclosporine concurrently or within the past 5 days. Note: recent or concurrent treatment with hydroxychloroquine or chloroquine is allowable, as these are 'non-biologic' DMARDs with potential antiviral activity.
• History of HIV infection and on active immunosuppressant therapy
• Current hematological or solid organ malignancy and on active immunosuppressant therapy
• Active tuberculosis (TB) infection or known or suspected systemic bacterial or fungal infection
• Pregnancy or breast feeding
• Known allergy to ruxolitinib
• In the opinion of the investigator, they are unlikely to survive for >48 hours from screening
• Any physical examination findings and/or history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

Additional Exclusion Criteria for Phase 2 only:

• Invasive oxygen supplementation, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO)

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Ruxolitinib
Participants will receive 10 mg ruxolitinib twice daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs)	Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. AEs will be collected and graded daily and cumulative incidence will be reported.	Day 0 (screening) through Day 29
Primary	Phase 2: Cumulative incidence of serious adverse events (SAEs)	An SAE is defined as an AE that is life-threatening or results in death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. SAEs will be collected and graded daily and cumulative incidence will be reported.	Day 0 (screening) through Day 29
Primary	Phase 2: Changes in white blood cell count (CBC) through Day 15	Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as standard of care (SOC). Mean changes from baseline to Day 15 will be reported.	Day 1 to Day 15
Primary	Phase 2: Changes in hemoglobin through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in platelets through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in creatinine through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in glucose through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in prothrombin time (PT) through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in total bilirubin through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in ALT through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in AST through Day 15		Day 1 to Day 15
Primary	Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS)	Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.	Day through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in hemoglobin through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in platelets through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in creatinine through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in glucose through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in prothrombin time (PT) though End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in total bilirubin through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in ALT through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 2: Changes in AST through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Primary	Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at Day 15	The 8-point ordinal scale described below, where a lower score indicates a worse outcome, will be performed daily or as recommended by participant's physician as SOC. The percent of participants scored at each severity will be reported on Day 15.; The 8-point ordinal scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 15
Secondary	Phase 2: Change in the 8-point ordinal scale		Day 1 to Day 29
Secondary	Phase 2: Change in National Early Warning Score (NEWS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Change in the 8-point ordinal scale		Day 1 to Day 29
Secondary	Phase 3: Change in National Early Warning Score (NEWS)		Day 1 to Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Time to an improvement of one category using the 8-point ordinal scale		Day 1 to Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Time to an improvement of two categories using the 8-point ordinal scale		Day 1 to Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Time to discharge or to a NEWS =2 and maintained for 24 hours, whichever occurs first		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs)		Day 0 (screening) through Day 29
Secondary	Phase 3: Cumulative incidence of serious adverse events (SAEs)		Day 0 (screening) through Day 29
Secondary	Phase 3: Duration of hospitalization		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Duration of new oxygen use		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Duration of new ventilator or ECMO use		Day 1 to Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Incidence of discontinuation or temporary suspension of drug for any reason		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Incidence of new oxygen use		Day 1 to Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Incidence of new ventilator use		Day 1 to Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Number of oxygen free days		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Number of ventilator or ECMO free days		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: 14 day mortality rate		Day 1 through Day 15
Secondary	Phase 3: 28 day mortality rate		Day 1 through Day 29
Secondary	Phase 3: Changes in white blood cell count (CBC) through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in hemoglobin through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in platelets through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in creatinine through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in glucose through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in prothrombin time (PT) through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in total bilirubin through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in ALT through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in AST through Day 15		Day 1 to Day 15
Secondary	Phase 3: Changes in white blood cell count (CBC) through End of Study (EOS)	Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.	Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in hemoglobin through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in platelets through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in creatinine through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in glucose through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in prothrombin time (PT) though End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in total bilirubin through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in ALT through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first
Secondary	Phase 3: Changes in AST through End of Study (EOS)		Day 1 through Day 29 or hospital discharge, whichever is first