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

• ClinicalTrials.gov Identifier: NCT03978637
• Recruitment Status: Active, not recruiting
• First Posted: June 7, 2019
• Last Update Posted: March 10, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Bronchiolitis Obliterans Syndrome	Drug: Itacitinib	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1 Itacitinib administered orally followed by phase 2; Itacitinib administered orally at the recommended dose from Phase 1.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 4, 2020
• Estimated Primary Completion Date: September 19, 2022
• Estimated Study Completion Date: September 19, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Itacitinib 300 mg; Phase 1: Itacitinib 300 mg twice daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.	Drug: Itacitinib; Itacitinib administered orally at the specified dose.; Other Name: INCB039110
Experimental: Itacitinib 400 mg; Phase 1: Itacitinib 400 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.	Drug: Itacitinib; Itacitinib administered orally at the specified dose.; Other Name: INCB039110
Experimental: Itacitinib 600 mg; Phase 1: Itacitinib 600 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration	Drug: Itacitinib; Itacitinib administered orally at the specified dose.; Other Name: INCB039110
Experimental: Itacitinib; Phase 2: Itacitinib administered orally at the recommended dose from Phase 1.	Drug: Itacitinib; Itacitinib administered orally at the specified dose.; Other Name: INCB039110

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Number of treatment-emergent adverse events [ Time Frame: Week 12 ]
   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.
2. Phase 1: Change from baseline in forced expiratory volume in 1 second (FEV1) [ Time Frame: Week 12 ]
3. Phase 2: Change from baseline in FEV1 response rate [ Time Frame: Week 12 ]
   Defined as the proportion of participants demonstrating a ≥ 10% absolute increase in FEV1 compared to baseline.

Secondary Outcome Measures :

1. Phase 1 and 2: Duration of FEV1 response [ Time Frame: Up to approximately 24 months ]
   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.
2. Phase 1 and 2: Time to progression [ Time Frame: Up to approximately 24 months ]
   Defined as the interval between the start of treatment and BOS progression (≥ 10% absolute decrease in FEV1 compared to baseline), or death.
3. Phase 1 and 2: Change from baseline in SGRQ total score [ Time Frame: Up to approximately 24 months ]
   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.
4. Phase 1 and 2: Change from baseline in QOL-SF-12 questionnaire [ Time Frame: Up to approximately 24 months ]
   A 12-item subset of the SF-36 v2 scale that will capture changes in health status during the course of treatment.
5. Phase 1 and 2: Categorical summary or change from baseline in EQ-5D-3L questionnaire [ Time Frame: Up to approximately 24 months ]
   A descriptive classification consisting of 5 dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort.
6. Phase 2: Overall Survival [ Time Frame: Up to approximately 24 months ]
   Defined as the interval between the start of treatment and the date of re-transplantation or death due to any cause.
7. Phase 1 and 2: Cmax of itacitinib [ Time Frame: Up to Week 4 ]
   Maximum observed concentration.
8. Phase 1 and 2: Cmin of itacitinib [ Time Frame: Up to Week 4 ]
   Minimum observed plasma or serum concentration over the dose interval.
9. Phase 1 and 2: Tmax of itacitinib [ Time Frame: Up to Week 4 ]
   Time to maximum concentration.
10. Phase 1 and 2: AUC0-t of itacitinib [ Time Frame: Up to Week 4 ]
    Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
11. Phase 1 and 2: Cl/F of itacitinib [ Time Frame: Up to Week 4 ]
    Apparent oral dose clearance.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, Los Angeles - David Geffen School of Medicine

Los Angeles, California, United States, 90095

United States, Massachusetts

Brigham and Women'S Faulkner Hospitals Inc

Boston, Massachusetts, United States, 02115

United States, North Carolina

Duke University Health System

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Temple University Department of Thoracic Medicine and Surgery

Philadelphia, Pennsylvania, United States, 19140

UPMC

Pittsburgh, Pennsylvania, United States, 15213

Belgium

Universitaire Ziekenhuis Leuven - Gasthuisberg

Leuven, Belgium, 03000

Canada, Ontario

University Health Network Toronto General Hospital

Toronto, Ontario, Canada, M5G 2N2

Sponsors and Collaborators

Incyte Corporation

Investigators

• Study Director: Kevin O'Hayer, MD; Incyte Corporation

More Information

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03978637
• Other Study ID Numbers: INCB 39110-214
• First Posted: June 7, 2019
• Last Update Posted: March 10, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:

Bronchiolitis obliterans syndrome; lung transplant; JAK1 inhibitor

Additional relevant MeSH terms:

Bronchiolitis; Bronchiolitis Obliterans; Syndrome; Disease; Pathologic Processes; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases