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

Primary Purpose

Bronchiolitis Obliterans Syndrome

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Itacitinib
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bronchiolitis Obliterans Syndrome focused on measuring Bronchiolitis obliterans syndrome, lung transplant, JAK1 inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California, Los Angeles - David Geffen School of Medicine
  • Brigham and Women'S Faulkner Hospitals Inc
  • Duke University Health System
  • Cleveland Clinic
  • Hospital of the University of Pennsylvania
  • Temple University Department of Thoracic Medicine and Surgery
  • UPMC
  • Universitaire Ziekenhuis Leuven - Gasthuisberg
  • University Health Network Toronto General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Itacitinib 300 mg

Itacitinib 400 mg

Itacitinib 600 mg

Itacitinib

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Phase 1: Number of treatment-emergent adverse events
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug until 30 days after the last dose of study drug.
Phase 1: Change from baseline in forced expiratory volume in 1 second (FEV1)
Phase 2: Change from baseline in FEV1 response rate
Defined as the proportion of participants demonstrating a ≥ 10% absolute increase in FEV1 compared to baseline.

Secondary Outcome Measures

Phase 1 and 2: Duration of FEV1 response
Defined as the time of the onset of response (≥ 10% absolute increase in FEV1 compared to baseline) to BOS progression or loss of clinical benefit as determined by the investigator.
Phase 1 and 2: Time to progression
Defined as the interval between the start of treatment and BOS progression (≥ 10% absolute decrease in FEV1 compared to baseline), or death.
Phase 1 and 2: Change from baseline in SGRQ total score
St. Georges Respiratory Questionnaire, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airway disease.
Phase 1 and 2: Change from baseline in QOL-SF-12 questionnaire
A 12-item subset of the SF-36 v2 scale that will capture changes in health status during the course of treatment.
Phase 1 and 2: Categorical summary or change from baseline in EQ-5D-3L questionnaire
A descriptive classification consisting of 5 dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort.
Phase 2: Overall Survival
Defined as the interval between the start of treatment and the date of re-transplantation or death due to any cause.
Phase 1 and 2: Cmax of itacitinib
Maximum observed concentration.
Phase 1 and 2: Cmin of itacitinib
Minimum observed plasma or serum concentration over the dose interval.
Phase 1 and 2: Tmax of itacitinib
Time to maximum concentration.
Phase 1 and 2: AUC0-t of itacitinib
Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
Phase 1 and 2: Cl/F of itacitinib
Apparent oral dose clearance.

Full Information

First Posted
June 5, 2019
Last Updated
August 4, 2023
Sponsor
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03978637
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 4, 2020 (Actual)
Primary Completion Date
September 29, 2023 (Anticipated)
Study Completion Date
September 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiolitis Obliterans Syndrome
Keywords
Bronchiolitis obliterans syndrome, lung transplant, JAK1 inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase 1 Itacitinib administered orally followed by phase 2; Itacitinib administered orally at the recommended dose from Phase 1.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Itacitinib 300 mg
Arm Type
Experimental
Arm Description
Phase 1: Itacitinib 300 mg twice daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.
Arm Title
Itacitinib 400 mg
Arm Type
Experimental
Arm Description
Phase 1: Itacitinib 400 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.
Arm Title
Itacitinib 600 mg
Arm Type
Experimental
Arm Description
Phase 1: Itacitinib 600 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration
Arm Title
Itacitinib
Arm Type
Experimental
Arm Description
Phase 2: Itacitinib administered orally at the recommended dose from Phase 1.
Intervention Type
Drug
Intervention Name(s)
Itacitinib
Other Intervention Name(s)
INCB039110
Intervention Description
Itacitinib administered orally at the specified dose.
Primary Outcome Measure Information:
Title
Phase 1: Number of treatment-emergent adverse events
Description
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug until 30 days after the last dose of study drug.
Time Frame
Up to approximately 24 months
Title
Phase 1: Change from baseline in forced expiratory volume in 1 second (FEV1)
Time Frame
Week 12
Title
Phase 2: Change from baseline in FEV1 response rate
Description
Defined as the proportion of participants demonstrating a ≥ 10% absolute increase in FEV1 compared to baseline.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Phase 1 and 2: Duration of FEV1 response
Description
Defined as the time of the onset of response (≥ 10% absolute increase in FEV1 compared to baseline) to BOS progression or loss of clinical benefit as determined by the investigator.
Time Frame
Up to approximately 24 months
Title
Phase 1 and 2: Time to progression
Description
Defined as the interval between the start of treatment and BOS progression (≥ 10% absolute decrease in FEV1 compared to baseline), or death.
Time Frame
Up to approximately 24 months
Title
Phase 1 and 2: Change from baseline in SGRQ total score
Description
St. Georges Respiratory Questionnaire, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airway disease.
Time Frame
Up to approximately 24 months
Title
Phase 1 and 2: Change from baseline in QOL-SF-12 questionnaire
Description
A 12-item subset of the SF-36 v2 scale that will capture changes in health status during the course of treatment.
Time Frame
Up to approximately 24 months
Title
Phase 1 and 2: Categorical summary or change from baseline in EQ-5D-3L questionnaire
Description
A descriptive classification consisting of 5 dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort.
Time Frame
Up to approximately 24 months
Title
Phase 2: Overall Survival
Description
Defined as the interval between the start of treatment and the date of re-transplantation or death due to any cause.
Time Frame
Up to approximately 24 months
Title
Phase 1 and 2: Cmax of itacitinib
Description
Maximum observed concentration.
Time Frame
Up to Week 4
Title
Phase 1 and 2: Cmin of itacitinib
Description
Minimum observed plasma or serum concentration over the dose interval.
Time Frame
Up to Week 4
Title
Phase 1 and 2: Tmax of itacitinib
Description
Time to maximum concentration.
Time Frame
Up to Week 4
Title
Phase 1 and 2: AUC0-t of itacitinib
Description
Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
Time Frame
Up to Week 4
Title
Phase 1 and 2: Cl/F of itacitinib
Description
Apparent oral dose clearance.
Time Frame
Up to Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin O'Hayer, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Los Angeles - David Geffen School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Brigham and Women'S Faulkner Hospitals Inc
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Temple University Department of Thoracic Medicine and Surgery
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Universitaire Ziekenhuis Leuven - Gasthuisberg
City
Leuven
ZIP/Postal Code
03000
Country
Belgium
Facility Name
University Health Network Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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

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