Clinical trial NCT03978637: Safety and Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung Transplantation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Bronchiolitis Obliterans Syndrome
Keywords: Bronchiolitis obliterans syndrome
lung transplant
JAK1 inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2019-06-07
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 Itacitinib administered orally followed by phase 2; Itacitinib administered orally at the recommended dose from Phase 1.
Primary purpose: TREATMENT

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).


Eligibility 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

  \*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.

Primary outcomes:
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to approximately 162 weeks
measure: Number of Participants With Any Grade 3 or Higher TEAE
timeFrame: up to approximately 162 weeks
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12
timeFrame: Baseline; Week 12
measure: Phase 2: FEV1 Response Rate
timeFrame: Baseline through Week 12
Secondary outcomes:
measure: Phase 1: Duration of FEV1 Response
timeFrame: up to 34.9 months
measure: Phase 2: Duration of FEV1 Response
timeFrame: up to 24 months
measure: Phase 1: Time to Progression
timeFrame: up to 36.4 months
measure: Phase 2: Time to Progression
timeFrame: up to 24 months
measure: Phase 1: Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score
timeFrame: Baseline; up to 158.4 weeks
measure: Phase 2: Change From Baseline in the SGRQ Total Score
timeFrame: up to 24 months
measure: Phase 1: Change From Baseline in the Quality of Life-Short Form-12 (QOL-SF-12) Questionnaire Scores
timeFrame: Baseline; up to 158.4 weeks
measure: Phase 2: Change From Baseline in QOL-SF-12 Questionnaire Scores
timeFrame: up to 24 months
measure: Phase 1: Number of Participants With the Indicated Responses on the EQ-5D-3L Questionnaire Regarding Their Health State
timeFrame: Baseline; up to 158.4 weeks
measure: Phase 2: Number of Participants With the Indicated Responses on the EQ-5D-3L Questionnaire Regarding Their Health State
timeFrame: up to 24 months
measure: Phase 1: Cmax of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
measure: Phase 2: Cmax of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose at Week 4
measure: Phase 1: AUC0-24h of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
measure: Phase 2: AUC0-24h of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose at Week 4
measure: Phase 1: Tmax of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
measure: Phase 2: Tmax of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose at Week 4
measure: Phase 1: Ctau of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4
measure: Phase 2: Ctau of Itacitanib
timeFrame: pre-dose and 1, 2, and 5 hours post-dose at Week 4
measure: Phase 2: Time to Retransplantation or Death
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles - David Geffen School of Medicine
state: California
city: Boston
country: United States
facility: Brigham and Women'S Faulkner Hospitals Inc
state: Massachusetts
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Department of Thoracic Medicine and Surgery
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Toronto
country: Canada
facility: University Health Network Toronto General Hospital
state: Ontario
Study officials:
affiliation: Incyte Corporation
name: Kevin O'Hayer, MD
role: STUDY_DIRECTOR
References: