Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury (iNSPIRE)

• ClinicalTrials.gov Identifier: NCT04375397
• Recruitment Status: Recruiting
• First Posted: May 5, 2020
• Last Update Posted: January 15, 2021
• Sponsor: AbbVie
• Collaborators: Janssen Research & Development, LLC; Pharmacyclics LLC (An AbbVie Company)
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: May 4, 2020
• First Posted Date: May 5, 2020
• Last Update Posted Date: January 15, 2021
• Actual Study Start Date: June 6, 2020
• Estimated Primary Completion Date: March 19, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 4, 2020)

Percentage of Participants Alive and Without Respiratory Failure [ Time Frame: Day 28 ]

Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 4, 2020)

• Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline [ Time Frame: Day 14 ]
  WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).
• Median Reduction in Days Spent on Supplemental Oxygen [ Time Frame: Up to Day 28 ]
  Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.
• All-Cause Mortality [ Time Frame: Up to Day 28 ]
  Percentage of participants with mortality from any cause.
• Percentage of Participants Experiencing Respiratory Failure or Death [ Time Frame: Up to Day 28 ]
  Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
• Mechanical Ventilation-Free Survival [ Time Frame: Up to Day 56 ]
  Percentage of participants alive and not requiring mechanical ventilation.
• Days on Mechanical Ventilation [ Time Frame: Up to Day 56 ]
  Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.
• Duration of hospitalization [ Time Frame: Up to Day 56 ]
  The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.
• Time to Discharge [ Time Frame: Up to Day 56 ]
  Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.
• Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio [ Time Frame: Up to Day 56 ]
  PaO2:FiO2 ratio is an index of respiratory distress.
• Oxygenation Index [ Time Frame: Up to Day 56 ]
  Oxygenation Index is a parameter of pulmonary function of participants.
• Number of Participants With Adverse Events [ Time Frame: Up to Day 56 ]
  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
• Number of Participants With Abnormal Laboratory Findings [ Time Frame: Up to Day 56 ]
  Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury
• Official Title: IbrutiNib in SARS CoV-2 Induced Pulmonary Injury and Respiratory Failure (iNSPIRE)

Brief Summary

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection.

Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States.

Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care.

There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: CoronaVirus Induced Disease-2019 (COVID-19)

Intervention

• Drug: Ibrutinib
  Oral Capsule
  Other Name: Imbruvica
• Drug: Placebo
  Oral Capsule

Study Arms

• Experimental: Ibrutinib
  Participants will receive Ibrutinib along with supportive care.
  Intervention: Drug: Ibrutinib
• Placebo Comparator: Placebo
  Participants will receive Placebo along with supportive care.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 4, 2020): 46
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 25, 2021
• Estimated Primary Completion Date: March 19, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Requires hospitalization for COVID-19 infection.
• Has Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) test before study entry.
• Requires supplemental oxygen for pulmonary distress related to COVID-19 infection, and has been on supplemental oxygen for no more than 5 days, and on breathing room air have oxygen saturation levels of 94% or less..
• Has radiographic evidence of pulmonary infiltrates.
• Females of childbearing potential (FCBP) must use 1 reliable form of contraception or have complete abstinence from heterosexual intercourse during the following time periods related to this study: while participating in the study; and for at least 1 month after discontinuation of study drug. FCBP must be referred to a qualified provider of contraceptive methods if needed. FCBP must have a negative serum pregnancy test as of screening.
• Men must agree to use a latex condom during treatment and for up to 3 months after the last dose of ibrutinib during sexual contact with a FCBP.
• Adequate hematologic, hepatic and renal function as described in the protocol.
• Must be within 10 days of confirmed diagnosis of COVID-19.

Exclusion Criteria:

• Respiratory failure at time of screening as defined per protocol with any of these following therapies:

  • Endotracheal intubation and mechanical ventilation.
  • Extracorporeal membrane oxygenation (ECMO).
  • High flow nasal cannula oxygen at flow rates >=30 L/min and fraction of delivered oxygen >= 0.5.
  • Non-invasive positive pressure ventilation.
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• On a BTK-inhibitor, anti-IL6, anti-IL6R, or Janus kinase inhibitor (JAKi).
• Has received rituximab within 180 days from study entry.
• Known bleeding disorders.
• Major surgery within 4 weeks of study entry.
• Participants in whom surgery is anticipated to be necessary within 72 hours.
• History of stroke or bleeding around or within brain within 6 months prior to enrollment.
• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Currently active, clinically significant cardiovascular disease.
• Asymptomatic arrythmias and or history of ejection fraction < 40% on an echo.
• Participants receiving a strong cytochrome P450 (CYP) 3A4 inhibitor with the exception of those receiving anti-fungal therapy/prophylaxis.
• Chronic liver disease and hepatic impairment meeting Child Pugh class C.
• Female participants who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 1 month of last dose of study drug. Male participants who plan to father a child while enrolled in this study or within 3 months after the last dose of study drug.
• Unwilling or unable to participate in all required study evaluations and procedures.
• Vaccinated with a live, attenuated vaccine within 4 weeks.
• Uncontrolled high blood pressure.
• On therapeutic anticoagulation at baseline.
• Participants with cancer.
• Co-enrolled in another interventional trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04375397
• Other Study ID Numbers: M20-310
• 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
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Requests for access to individual participant data from ibrutinib clinical studies conducted by AbbVie can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu
• URL: http://yoda.yale.edu/

• Responsible Party: AbbVie
• Study Sponsor: AbbVie

Collaborators

• Janssen Research & Development, LLC
• Pharmacyclics LLC (An AbbVie Company)

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: January 2021