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

• ClinicalTrials.gov Identifier: NCT03978637
• Recruitment Status: Recruiting
• First Posted: June 7, 2019
• Last Update Posted: December 20, 2019
• 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)
• Estimated Enrollment: 75 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: September 9, 2019
• Estimated Primary Completion Date: December 9, 2020
• Estimated Study Completion Date: September 16, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Itacitinib 200 mg; Phase 1: Itacitinib 200 mg once daily.	Drug: Itacitinib; Itacitinib administered orally at the specified dose.; Other Name: INCB039110
Experimental: Itacitinib 400 mg; Phase 1: Itacitinib 400 mg once daily.	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).
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 1 and 2: Cmax of itacitinib [ Time Frame: Up to Week 4 ]
   Maximum observed concentration.
7. Phase 1 and 2: Cmin of itacitinib [ Time Frame: Up to Week 4 ]
   Minimum observed plasma or serum concentration over the dose interval.
8. Phase 1 and 2: Tmax of itacitinib [ Time Frame: Up to Week 4 ]
   Time to maximum concentration.
9. 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.
10. 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

OR

*Confirmed BOS 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

Contacts

Contact: Incyte Corporation Call Center (US); 1.855.463.3463; medinfo@incyte.com

Contact: Incyte Corporation Call Center (ex-US); +800 00027423; globalmedinfo@incyte.com

Locations

United States, California

University of California, Los Angeles; Not yet recruiting

Los Angeles, California, United States, 90095

United States, Massachusetts

Massachusetts General Hospital; Not yet recruiting

Boston, Massachusetts, United States, 02114

Brigham and Women's Hospital Pulmonary Division, Clinic 3; Not yet recruiting

Boston, Massachusetts, United States, 02115

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

University of Pennsylvania; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19104

Temple University Department of Thoracic Medicine and Surgery; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19140

University of Pittsburgh Medical Center Falk Medical Building (Comprehensive Lung Center); Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Belgium

Universitaire Ziekenhuis Leuven-Gasthuisberg; Not yet recruiting

Leuven, Belgium, 3000

Canada

University Health Network Toronto General Hospital; Not yet recruiting

Toronto, 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: December 20, 2019
• Last Verified: December 2019

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; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Infections