Study to Evaluate the Effect of GBT440 Administered to Subjects With IPF on Supplemental Oxygen at Rest

Study Overview
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Brief Summary
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This is an open label study in which eligible IPF subjects who are using supplemental oxygen at rest will receive GBT440 orally daily.

Official Title
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A Phase II Open Label Study to Evaluate the Effect of GBT440 on Hypoxemia in Subjects With Idiopathic Pulmonary Fibrosis (IPF) Who Are Using Supplemental Oxygen at Rest (ZEPHYR)

Conditions
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Idiopathic Pulmonary Fibrosis, Hypoxemia

Intervention / Treatment
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* Drug: GBT440


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of IPF. Receiving supplemental oxygen for use at rest. Weight ≥ 40 kg. Male or female of child bearing potential willing and able to use highly effective methods of contraception from study start to 30 days after the last dose of study drug. Exclusion Criteria: FEV1/FVC < 70% History of other interstitial lung diseases. Subject plans to begin or has commenced pulmonary rehabilitation within 30 days of screening. Corticosteroid (> 10 mg per day of prednisone or an equivalent) administered for 7 days or longer, within 30 days of screening. Participated in another clinical trial of an investigational drug (or medical device) within 30 days or 5-half-lives, whichever is longer, prior to screening, or is currently participating in another trial of an investigational drug (or medical device). Female who is breast-feeding or pregnant Current smoker or history of smoking within 3 months from screening

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBT440 900 mg Dose<br>Part A, 900 mg GBT440: Capsules which contain GBT440 drug substance in Swedish orange | Drug: GBT440<br>* GBT440: Capsules which contain GBT440 drug substance in Swedish orange<br>|
| Experimental: GBT440 1500 mg Dose<br>Part B , 1500 mg GBT440: Capsules which contain GBT440 drug substance in Swedish orange | Drug: GBT440<br>* GBT440: Capsules which contain GBT440 drug substance in Swedish orange<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Oxygen Saturation at End of Treatment Period Compared to Baseline |  | Days 1 to 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Supplemental Oxygen Requirement at End of Treatment Period Compared to Baseline |  | Days 1 to 90 | 
| Evaluate the Effect of GBT440 on Resting and Post-exercise Alveolar-arterial O2 Tension Difference [P(A-a) O2] at End of Treatment Period Compared to Baseline |  | Days 1 to 90 | 
| Evaluate the Effect of GBT440 on Performance of the 6MWT |  | Days 1 to 90 | 
| Evaluate the Effect of GBT440 on IPF Related Symptoms Using Patient Related Outcomes |  | Days 1 to 90 | 
| Evaluate Pulmonary Function Using Pulmonary Function Tests (FVC and DLco) | Spirometry measurements will include forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLco). | Days 1 to 90 | 
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 |  | Days 1 to 90 | 
| Pharmacokinetic Parameters of GBT440 in Plasma and Whole Blood (Minimum Concentration (Cmin)) | PK parameters of GBT440 administered daily orally for 90 days in plasma and whole blood, including but not limited to, minimum concentration (Cmin), at steady state. | Day 1 (15 mins post-dose and 2-4h post-dose), Day 15 (pre-dose), Day 30 (pre-dose), Day 60 (pre-dose and 2-4h post-dose), Day 90 (pre-dose), Day 105 (during study visit), and Day 120 (during study visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic pulmonary fibrosis, hypoxemia, oxygen