Trial Outcomes & Findings for Safety and Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung Transplantation (NCT NCT03978637)

Last Updated: 2025-10-20

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

up to approximately 162 weeks

Results posted on

2025-10-20

Participant Flow

This study was conducted at 7 study centers in the United States, Canada, and Belgium. The site in Canada had a screen failure but did not recruit any participants.

Participant milestones

Participant milestones
Measure	Itacitinib 300/200 mg Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Overall Study STARTED	7	7	8	1
Overall Study COMPLETED	6	2	3	1
Overall Study NOT COMPLETED	1	5	5	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Itacitinib 300/200 mg Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Overall Study Death	0	2	2
Overall Study Withdrawal by Subject	0	0	1
Overall Study Transitioned to Itacitinib Rollover Trial	1	3	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Itacitinib 300/200 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg n=8 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other n=1 Participants Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	17 Participants n=21 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Sex/Gender, Customized Female	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Sex/Gender, Customized Male	5 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	0 Participants n=4 Participants	17 Participants n=21 Participants
Race/Ethnicity, Customized White/Caucasian	6 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	1 Participants n=4 Participants	20 Participants n=21 Participants
Race/Ethnicity, Customized Black/African-American	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	1 Participants n=4 Participants	21 Participants n=21 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: up to approximately 162 weeks

Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of itacitinib

Outcome measures

Outcome measures
Measure	Itacitinib 300/200 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg n=8 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other n=1 Participants Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitininb 600 mg QD Participants received itacitinib 600 mg QD during the course of the study. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	7 Participants	7 Participants	8 Participants	1 Participants	—

PRIMARY outcome

Timeframe: up to approximately 162 weeks

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Itacitinib 300/200 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg n=8 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other n=1 Participants Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitininb 600 mg QD Participants received itacitinib 600 mg QD during the course of the study. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Number of Participants With Any Grade 3 or Higher TEAE	6 Participants	7 Participants	6 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Baseline; Week 12

Population: Full Analysis Set. Only participants with available data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Itacitinib 300/200 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg n=7 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg n=8 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other n=1 Participants Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitininb 600 mg QD Participants received itacitinib 600 mg QD during the course of the study. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12 Baseline	1.72 liters Standard Deviation 0.962	1.57 liters Standard Deviation 0.672	1.59 liters Standard Deviation 0.511	1.34 liters Standard Deviation NA Standard deviation cannot be reported for a single participant.	—
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12 Change from Baseline	0.09 liters Standard Deviation 0.168	0.04 liters Standard Deviation 0.114	0.22 liters Standard Deviation 0.571	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Itacitinib 300/200 mg n=1 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg n=1 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg n=6 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other n=6 Participants Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitininb 600 mg QD n=6 Participants Participants received itacitinib 600 mg QD during the course of the study. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Phase 1: Tmax of Itacitanib	2.15 hours Full range cannot be reported for a single participant.	4.63 hours Full range cannot be reported for a single participant.	3.2 hours Interval 1.8 to 4.5	2.0 hours Interval 1.8 to 4.1	1.9 hours Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: pre-dose and 1, 2, and 5 hours post-dose at Week 4

Population: 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.

tmax was defined as the time to the maximum observed concentration of itacitanib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4

Ctau was defined as the observed itacitanib concentration at the end of the dosing interval.

Outcome measures

Outcome measures
Measure	Itacitinib 300/200 mg n=1 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 milligrams (mg) twice daily (BID). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 200 mg BID. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 400/300 mg n=1 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg once daily (QD). Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 300 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitinib 600/400 mg n=5 Participants Participants not taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 600 mg QD. Participants taking a concomitant strong CYP3A inhibitor received a starting dose of itacitinib 400 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Other n=6 Participants Participants received a starting dose of itacitinib 200 mg QD. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.	Itacitininb 600 mg QD n=6 Participants Participants received itacitinib 600 mg QD during the course of the study. Participants may have had dose reductions or modifications during the course of treatment based on adverse events, clinical evaluation, changes to concomitant medications, and laboratory assessments. Itacitinib treatment was continued until progression of bronchiolitis obliterans syndrome (defined as a ≥10% absolute decrease from Baseline in forced expiratory volume in 1 second (FEV1), confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.
Phase 1: Ctau of Itacitanib	9.34 nmol/L Geometric Coefficient of Variation NA Dispersion cannot be reported for a single participant.	403 nmol/L Geometric Coefficient of Variation NA Dispersion cannot be reported for a single participant.	510 nmol/L Geometric Coefficient of Variation 130	16.5 nmol/L Geometric Coefficient of Variation 675	43.4 nmol/L Geometric Coefficient of Variation 92.7

SECONDARY outcome

Timeframe: pre-dose and 1, 2, and 5 hours post-dose at Week 4

Population: 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.

Ctau was defined as the observed itacitanib concentration at the end of the dosing interval.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

Itacitinib 300/200 mg

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Itacitinib 400/300 mg

Serious events: 7 serious events

Other events: 7 other events

Deaths: 2 deaths

Itacitinib 600/400 mg

Serious events: 6 serious events

Other events: 7 other events

Deaths: 2 deaths

Other

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 1-855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER