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

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

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).

Study Overview

• Status: Terminated
• Conditions: Bronchiolitis Obliterans Syndrome
• Intervention / Treatment: Drug: Itacitinib

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network Toronto General Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles - David Geffen School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women'S Faulkner Hospitals Inc
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Department of Thoracic Medicine and Surgery
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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 Names: INCB039110

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Duration of FEV1 Response	Duration of FEV1 response was defined as the interval between the onset of response and the earliest of bronchiolitis obliterans syndrome (BOS) progression, loss of clinical benefit as determined by the investigator, or death.	up to 34.9 months
Phase 2: Duration of FEV1 Response	Duration of FEV1 response was defined as the interval between the onset of response and the earliest of bronchiolitis obliterans syndrome progression, loss of clinical benefit as determined by the investigator, or death.	up to 24 months
Phase 1: Time to Progression	Time to progression was defined as defined as the interval between the start of treatment and bronchiolitis obliterans syndrome progression (≥10% absolute decrease in FEV1 compared to baseline), or death.	up to 36.4 months
Phase 2: Time to Progression	Time to progression was defined as defined as the interval between the start of treatment and bronchiolitis obliterans syndrome progression (≥10% absolute decrease in FEV1 compared to baseline), or death.	up to 24 months
Phase 1: Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score	The SGRQ is a disease-specific instrument designed to measure the impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. It consists of 50 items covering 3 domains: symptoms (8 items), activity (16 items), and impacts (26 items). A component score is calculated for each of the 3 domains. One total score is calculated if none of the component scores is missing. All scales (both domain and total) have a score ranging between 0 and 100, with higher scores indicating a worse quality of life. Change from (CFB) Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline; up to 158.4 weeks
Phase 2: Change From Baseline in the SGRQ Total Score	The SGRQ is a disease-specific instrument designed to measure the impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. It consists of 50 items covering 3 domains: symptoms (8 items), activity (16 items), and impacts (26 items). A component score is calculated for each of the 3 domains. One total score is calculated if none of the component scores is missing. All scales (both domain and total) have a score ranging between 0 and 100, with higher scores indicating a worse quality of life. Change from Baseline was to be calculated as the post-Baseline value minus the Baseline value.	up to 24 months
Phase 1: Change From Baseline in the Quality of Life-Short Form-12 (QOL-SF-12) Questionnaire Scores	The QOL-SF-12 v2 is a 12-item subset of the QOL-SF-36 v2 scale that assesses 8 health concepts related to limitations in physical activities, social activities (SA), bodily pain, general mental and physical health, and vitality. Participants answered each question by selecting pre-specified choices. Score ranges are specified for each item; higher scores indicate better health. Assessment of health score: poor (1) to excellent (5). Moderate activities and climbing stairs score: limited a lot (1) to not limited at all (3). Accomplished less because of physical health (PH) or emotional problems (EP)/limited in work/did work less carefully score: all of the time (1) to none of the time (5). Pain interfered with work score: extremely (1) to not at all (5). Felt calm/peaceful, had a lot of energy, felt depressed, PH or EP interfered with SA score: none of the time (1) to all of the time (6). Change from Baseline (BL) was calculated as the post-BL value minus the BL value.	Baseline; up to 158.4 weeks
Phase 2: Change From Baseline in QOL-SF-12 Questionnaire Scores	The QOL-SF-12 v2 is a 12-item subset of the QOL-SF-36 v2 scale that assesses 8 health concepts related to limitations in physical activities, social activities (SA), bodily pain, general mental and physical health, and vitality. Participants answered each question by selecting pre-specified choices. Score ranges are specified for each item; higher scores indicate better health. Assessment of health score: poor (1) to excellent (5). Moderate activities and climbing stairs score: limited a lot (1) to not limited at all (3). Accomplished less because of physical health (PH) or emotional problems (EP)/limited in work/did work less carefully score: all of the time (1) to none of the time (5). Pain interfered with work score: extremely (1) to not at all (5). Felt calm/peaceful, had a lot of energy, felt depressed, PH or EP interfered with SA score: none of the time (1) to all of the time (6). Change from Baseline (BL) was to be calculated as the post-BL value minus the BL value.	up to 24 months
Phase 1: Number of Participants With the Indicated Responses on the EQ-5D-3L Questionnaire Regarding Their Health State	The EQ-5D-3L essentially consists of 2 components: the EQ-5D descriptive scale and the EQ-VAS. The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. Each dimension has 3 levels: no problems, some problems, and extreme problems. At each specific visit (starting on Day 1), the participant was asked to indicate their health state. BL=Baseline; EOT=end of treatment.	Baseline; up to 158.4 weeks
Phase 2: Number of Participants With the Indicated Responses on the EQ-5D-3L Questionnaire Regarding Their Health State	The EQ-5D-3L essentially consists of 2 components: the EQ-5D descriptive scale and the EQ-VAS. The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. Each dimension has 3 levels: no problems, some problems, and extreme problems. At each specific visit (starting on Day 1), the participant was asked to indicate their health state.	up to 24 months
Phase 1: Cmax of Itacitanib	Cmax was defined as the maximum observed concentration of itacitanib.	pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
Phase 2: Cmax of Itacitanib	Cmax was defined as the maximum observed concentration of itacitanib.	pre-dose and 1, 2, and 5 hours post-dose at Week 4
Phase 1: AUC0-24h of Itacitanib	AUC0-24h was defined as the area under the plasma concentration-time curve over the last 24-hour dosing interval.	pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
Phase 2: AUC0-24h of Itacitanib	AUC0-24h was defined as the area under the plasma concentration-time curve over the last 24-hour dosing interval.	pre-dose and 1, 2, and 5 hours post-dose at Week 4
Phase 1: Tmax of Itacitanib	tmax was defined as the time to the maximum observed concentration of itacitanib.	pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
Phase 2: Tmax of Itacitanib	tmax was defined as the time to the maximum observed concentration of itacitanib.	pre-dose and 1, 2, and 5 hours post-dose at Week 4
Phase 1: Ctau of Itacitanib	Ctau was defined as the observed itacitanib concentration at the end of the dosing interval.	pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
Phase 2: Ctau of Itacitanib	Ctau was defined as the observed itacitanib concentration at the end of the dosing interval.	pre-dose and 1, 2, and 5 hours post-dose at Week 4
Phase 2: Time to Retransplantation or Death	Time to retransplantation or death was defined as the interval between the start of treatment and the date of retransplantation or death due to any cause.	up to 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): October 13, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 15, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: lung transplant; Bronchiolitis obliterans syndrome; JAK1 inhibitor
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; itacitinib; INCB039110
• Other Study ID Numbers: INCB 39110-214; 2019-004171-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No