INCB 39110-214

Incyte Corporation

1801 Augustine Cutoff Drive, Wilmington, United States, 19803

Study Director, Incyte Corporation, 1 554633463, medinfo@incyte.com

Study Director, Incyte Corporation, 1 554633463, medinfo@incyte.com

No

No

No

Final

13 Oct 2023

No

Yes

13 Oct 2023

Yes

Phase 1: To identify an appropriate dose of itacitinib as a treatment for Grade 1 through 3 Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation. Phase 2: To evaluate the efficacy of itacitinib as a treatment for Grade 1 through 3 BOS following lung transplantation.

This study was to be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the United States Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as International Conference on Harmonisation Good Clinical Practice (ICH GCP) consolidated guidelines (E6) and applicable regulatory requirements.

04 Feb 2020

No

No

Belgium: 7

United States: 16

23

7

0

0

0

0

0

0

17

6

0

Overall Study (overall period)

Randomised - controlled

Yes

itacitinib

Prolonged-release tablet

Oral use

100-milligram prolonged-release tablets

itacitinib

Prolonged-release tablet

Oral use

100-milligram prolonged-release tablets

itacitinib

Prolonged-release tablet

Oral use

100-milligram prolonged-release tablets

itacitinib

Prolonged-release tablet

Oral use

100-milligram prolonged-release tablets

Itacitinib 300/200 mg

Itacitinib 400/300 mg

Itacitinib 600/400 mg

Other

Itacitinib 300/200 mg

Itacitinib 400/300 mg

Itacitinib 600/400 mg

Other

Itacitinib 200 mg QD

Participants in the PK-Evaluable Population received itacitinib 200 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.

Itacitinib 300 mg QD

Participants in the PK-Evaluable Population received itacitinib 300 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 FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.

Itacitinib 300 mg BID

Participants in the PK-Evaluable Population received itacitinib 300 mg BID 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 FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.

Itacitinib 400 mg QD

Participants in the PK-Evaluable Population received itacitinib 400 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 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 in the PK-Evaluable Population 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 FEV1, confirmed by 2 consecutive spirometric assessments ≥3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of consent.

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.

Primary

up to approximately 162 weeks

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.

Primary

up to approximately 162 weeks

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. 9999=Mean (SD) data cannot be reported for a single participant due to privacy concerns. 8888=No participants were analyzed at this time point.

Primary

Baseline; Week 12

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. -9999, 9999=The median and the upper and lower limits of the confidence interval were not estimable because there were too few events of bronchiolitis obliterans syndrome progression or loss of clinical benefit.

Secondary

up to 34.9 months

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. -9999, 9999=The median and the upper and lower limits of the confidence interval were not estimable because too few participants had disease progression or died.

Secondary

up to 36.4 months

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 was to be calculated for each of the 3 domains. One total score was to be calculated if none of the component scores was 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.

Secondary

Baseline; up to 158.4 weeks

The QOL-SF-12 v2 is a 12-item subset of the QOL-SF-36 v2 scale that captures changes in health status during the course of treatment. The QOL-SF-12 assesses 8 health concepts related to limitations in physical activities, social activities, bodily pain, general mental and physical health, and vitality. For this questionnaire, 1 component score was to be provided for each of 8 health concepts. Two summary scores, physical component summary and mental component summary, were also to be provided. For each item, scores range from 0 to 100; a higher score indicates a better health state. Change from Baseline was to be calculated as the post-Baseline value minus the Baseline value.

Secondary

Baseline; up to 158.4 weeks

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. The EQ-VAS records the respondent's self-rated health on a vertical visual analog scale on which the endpoints are labeled as "the best health you can imagine" and "the worst health you can imagine." At each specific visit (starting on Day 1), the participant was to be asked to indicate their health state. The categorical outcomes for the 5 dimensions (mobility, self-care, usual activities, anxiety/depression, and pain/discomfort) were to be reported. The change from Baseline in the EQ-VAS score was to be reported. Change from Baseline was to be calculated as the post-Baseline value minus the Baseline value.

Secondary

Baseline; up to 158.4 weeks

Cmax was defined as the maximum observed concentration of itacitanib. Participants in the Pharmacokinetic (PK)-Evaluable Population, defined as all enrolled participants who received at least 1 dose of itacitinib and provided at least 1 post-dose PK sample, have been analyzed. Data were analyzed by dose rather than by treatment arm because approximately one-third of the participants had a dose adjustment (dose reduction) during the course of the study. 9999=Data cannot be reported for a single participant due to privacy concerns.

Secondary

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. Data were analyzed by dose rather than by treatment arm because approximately one-third of the participants had a dose adjustment (dose reduction) during the course of the study. 9999=Data cannot be reported for a single participant due to privacy concerns.

Secondary

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

tmax was defined as the time to the maximum observed concentration of itacitanib. Data were analyzed by dose rather than by treatment arm because approximately one-third of the participants had a dose adjustment (dose reduction) during the course of the study. -9999, 9999=Data cannot be reported for a single participant due to privacy concerns.

Secondary

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

AUC0-24h was defined as the area under the plasma concentration-time curve over the last 24-hour dosing interval. Data were analyzed by dose rather than by treatment arm because approximately one-third of the participants had a dose adjustment (dose reduction) during the course of the study. 9999=Data cannot be reported for a single participant due to privacy concerns.

Secondary

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

up to approximately 162 weeks

Treatment-emergent adverse events, defined as either adverse events reported for the first time or the worsening of pre-existing conditions after the first dose of itacitinib until 30 days after the last dose of itacitinib, have been reported.

26.1

Itacitinib 300/200 mg

Itacitinib 600/400 mg

Other

Itacitinib 400/300 mg