Safety and Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung Transplantation

Bronchiolitis Obliterans Syndrome Clinical Trial

Official title:

An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03978637
• Other study ID #: INCB 39110-214
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 4, 2020
• Est. completion date: October 13, 2023

Study information

• Verified date: November 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of itacitinib in participants with post-lung transplant bronchiolitis obliterans syndrome (BOS).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: October 13, 2023
• Est. primary completion date: October 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Double lung transplantation = 1 year before informed consent. Confirmed BOS progression to Grade 1, 2, or 3 diagnosed within 1 year of screening *Confirmed BOS progression to Grade 1, 2, or 3 diagnosed within 2 years of screening

AND:

• A = 200 mL decrease in FEV1 in the previous 12 months OR *A = 50 mL decrease in FEV1 in the last 2 measurements.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• History of a single lung transplant
• FEV1 decline attributable to cause(s) other than BOS.
• Participants who have had any significant change (eg, addition of new agents) in an immunosuppressive regimen in the 4 weeks before screening.
• Untreated and/or symptomatic gastroesophageal reflux disease.
• Significant infectious comorbidities including invasive fungal disease, B. Cepacia, non TB mycobacteria, or TB.
• Receipt of JAK inhibitor therapy after lung transplant for any indication. Treatment with a JAK inhibitor before lung transplant is permitted.
• Laboratory values at screening outside the protocol-defined ranges.
• Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (ie, positive HBsAg).
• Known HIV infection.
• History of active malignancy within 3 years of screening.
• Women who are pregnant or breastfeeding.
• Treatment with an investigational agent, procedure, or device within 30 days of enrollment, or within 5 half-lives of the investigational product, whichever is longer.

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Bronchiolitis Obliterans Syndrome
• Syndrome

Intervention

Drug:
• Itacitinib
Itacitinib administered orally at the specified dose.

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
Canada	University Health Network Toronto General Hospital	Toronto	Ontario
United States	Brigham and Women'S Faulkner Hospitals Inc	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University Health System	Durham	North Carolina
United States	University of California, Los Angeles - David Geffen School of Medicine	Los Angeles	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University Department of Thoracic Medicine and Surgery	Philadelphia	Pennsylvania
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of treatment-emergent adverse events	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug until 30 days after the last dose of study drug.	Up to approximately 24 months
Primary	Phase 1: Change from baseline in forced expiratory volume in 1 second (FEV1)		Week 12
Primary	Phase 2: Change from baseline in FEV1 response rate	Defined as the proportion of participants demonstrating a = 10% absolute increase in FEV1 compared to baseline.	Week 12
Secondary	Phase 1 and 2: Duration of FEV1 response	Defined as the time of the onset of response (= 10% absolute increase in FEV1 compared to baseline) to BOS progression or loss of clinical benefit as determined by the investigator.	Up to approximately 24 months
Secondary	Phase 1 and 2: Time to progression	Defined as the interval between the start of treatment and BOS progression (= 10% absolute decrease in FEV1 compared to baseline), or death.	Up to approximately 24 months
Secondary	Phase 1 and 2: Change from baseline in SGRQ total score	St. Georges Respiratory Questionnaire, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airway disease.	Up to approximately 24 months
Secondary	Phase 1 and 2: Change from baseline in QOL-SF-12 questionnaire	A 12-item subset of the SF-36 v2 scale that will capture changes in health status during the course of treatment.	Up to approximately 24 months
Secondary	Phase 1 and 2: Categorical summary or change from baseline in EQ-5D-3L questionnaire	A descriptive classification consisting of 5 dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort.	Up to approximately 24 months
Secondary	Phase 2: Overall Survival	Defined as the interval between the start of treatment and the date of re-transplantation or death due to any cause.	Up to approximately 24 months
Secondary	Phase 1 and 2: Cmax of itacitinib	Maximum observed concentration.	Up to Week 4
Secondary	Phase 1 and 2: Cmin of itacitinib	Minimum observed plasma or serum concentration over the dose interval.	Up to Week 4
Secondary	Phase 1 and 2: Tmax of itacitinib	Time to maximum concentration.	Up to Week 4
Secondary	Phase 1 and 2: AUC0-t of itacitinib	Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.	Up to Week 4
Secondary	Phase 1 and 2: Cl/F of itacitinib	Apparent oral dose clearance.	Up to Week 4