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

NCT03978637 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: INCB 39110-2142019-004171-39
• Study Type: interventional
• Target: 23
• Locations: 3 countries
• Sites: 9

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).

Conditions

Bronchiolitis Obliterans Syndrome

Keywords

Bronchiolitis obliterans syndrome; lung transplant; JAK1 inhibitor

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

  An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as either an AE reported for the first time or the worsening of a pre-existing condition after the first dose of itacitinib until 30 days after the last dose of itacitinib.

  up to approximately 162 weeks

• Number of Participants With Any Grade 3 or Higher TEAE

  An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as either an AE reported for the first time or the worsening of a pre-existing condition after the first dose of itacitinib until 30 days after the last dose of itacitinib. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

  up to approximately 162 weeks

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12

  FEV1 was defined as the volume of air exhaled in 1 second. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  Baseline; Week 12

• Phase 2: FEV1 Response Rate

  FEV1 response rate was defined as the percentage of participants demonstrating a ≥10% absolute increase in FEV1 compared with Baseline, confirmed by 2 consecutive spirometric assessments ≥1 week apart.

  Baseline through Week 12

Secondary Outcomes (19)

• Phase 1: Duration of FEV1 Response

  up to 34.9 months

• Phase 2: Duration of FEV1 Response

  up to 24 months

• Phase 1: Time to Progression

  up to 36.4 months

• Phase 2: Time to Progression

  up to 24 months

• Phase 1: Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score

  Baseline; up to 158.4 weeks

Study Arms (4)

Itacitinib 300 mg

EXPERIMENTAL

Phase 1: Itacitinib 300 mg twice daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.

Drug: Itacitinib

Itacitinib 400 mg

EXPERIMENTAL

Phase 1: Itacitinib 400 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.

Drug: Itacitinib

Itacitinib 600 mg

EXPERIMENTAL

Phase 1: Itacitinib 600 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration

Drug: Itacitinib

Itacitinib

EXPERIMENTAL

Phase 2: Itacitinib administered orally at the recommended dose from Phase 1.

Drug: Itacitinib

Interventions

Itacitinib DRUG

Itacitinib administered orally at the specified dose.

Also known as: INCB039110

Itacitinib; Itacitinib 300 mg; Itacitinib 400 mg; Itacitinib 600 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \*A ≥ 50 mL decrease in FEV1 in the last 2 measurements.
• Willingness to avoid pregnancy or fathering children.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (9)

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

Los Angeles, California, 90095, United States

Location

Brigham and Women'S Faulkner Hospitals Inc

Boston, Massachusetts, 02115, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Department of Thoracic Medicine and Surgery

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Universitaire Ziekenhuis Leuven - Gasthuisberg

Leuven, 03000, Belgium

Location

University Health Network Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

itacitinib; INCB039110

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Limitations and Caveats

A business decision was made to terminate the study before the initiation of Part 2. The decision to terminate the study was unrelated to safety concerns. Results from Phase 1 of the study have been reported in this summary.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Kevin O'Hayer, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 Itacitinib administered orally followed by phase 2; Itacitinib administered orally at the recommended dose from Phase 1.

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 7, 2019
• Study Start: February 4, 2020
• Primary Completion: October 13, 2023
• Study Completion: October 13, 2023
• Last Updated: October 20, 2025
• Results First Posted: January 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (7); BE (1)