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Bronchiolitis Obliterans SyndromePhase 1/2NCT03978637

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

A Phase 1/2 study testing Itacitinib in people with Bronchiolitis Obliterans Syndrome, run by Incyte Corporation at 9 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bronchiolitis Obliterans Syndrome
What is being tested?
Itacitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
9 sitesin 3 countries
Study dates
4 Feb 2020to 13 Oct 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States7 sites
  • Brigham and Women'S Faulkner Hospitals Inc

    Boston, Massachusetts, 02115

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Duke University Health System

    Durham, North Carolina, 27710

  • University of California, Los Angeles - David Geffen School of Medicine

    Los Angeles, California, 90095

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Temple University Department of Thoracic Medicine and Surgery

    Philadelphia, Pennsylvania, 19140

  • UPMC

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

Belgium1 site
  • Universitaire Ziekenhuis Leuven - Gasthuisberg

    Leuven, 03000

Other trials in Belgium

Canada1 site
  • University Health Network Toronto General Hospital

    Toronto, Ontario, M5G 2N2

Other trials in Canada

About this study

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

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).

Being tested
Itacitinib
Keywords
Bronchiolitis obliterans syndrome, lung transplant, JAK1 inhibitor
Medical subject headings
Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ItacitinibDrug

    Also called INCB039110

    Itacitinib administered orally at the specified dose.

Study groups in NCT03978637
Study groupRoleWhat they receive
Itacitinib 300 mgExperimentalPhase 1: Itacitinib 300 mg twice daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.
Receives: Drug: Itacitinib
Itacitinib 400 mgExperimentalPhase 1: Itacitinib 400 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.
Receives: Drug: Itacitinib
Itacitinib 600 mgExperimentalPhase 1: Itacitinib 600 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration
Receives: Drug: Itacitinib
ItacitinibExperimentalPhase 2: Itacitinib administered orally at the recommended dose from Phase 1.
Receives: Drug: Itacitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to approximately 162 weeks

  2. 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.

    Measured: up to approximately 162 weeks

  3. 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.

    Measured: Baseline; Week 12

  4. 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.

    Measured: Baseline through Week 12

Secondary outcomes (19)
  1. 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.

    Measured: up to 34.9 months

  2. 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.

    Measured: up to 24 months

  3. 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.

    Measured: up to 36.4 months

  4. 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.

    Measured: up to 24 months

  5. 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.

    Measured: Baseline; up to 158.4 weeks

  6. 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.

    Measured: up to 24 months

  7. 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.

    Measured: Baseline; up to 158.4 weeks

  8. 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.

    Measured: up to 24 months

  9. 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.

    Measured: Baseline; up to 158.4 weeks

  10. 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.

    Measured: up to 24 months

  11. Phase 1: Cmax of Itacitanib

    Cmax was defined as the maximum observed concentration of itacitanib.

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

  12. Phase 2: Cmax of Itacitanib

    Cmax was defined as the maximum observed concentration of itacitanib.

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

  13. 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.

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

  14. 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.

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

  15. Phase 1: Tmax of Itacitanib

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

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

  16. Phase 2: Tmax of Itacitanib

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

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

  17. Phase 1: Ctau of Itacitanib

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

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

  18. Phase 2: Ctau of Itacitanib

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

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

  19. 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.

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2019
  2. Study start4 Feb 2020
  3. Primary completion13 Oct 2023
  4. Study completion13 Oct 2023

Why it stopped: Business Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03978637
Sponsor's protocol ID
INCB 39110-214
Other IDs
2019-004171-39, 2019
Status last verified
Oct 2025
First submitted
5 Jun 2019
Last updated
20 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Itacitinib in people with Bronchiolitis Obliterans Syndrome, run by Incyte Corporation at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Belgium, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Treatment-emergent Adverse Event (TEAE) (time frame: up to approximately 162 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2025.

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