GBT440-026

Principal Investigator: Mary  Scholand
Keywords: IPF , Idiopathic Pulmonary Fibrosis , ILD , Interstitital Lung Disease Department: Pulmonary
IRB Number: 00095050 Co Investigator:  
Specialty: Pulmonary, Pulmonary, Pulmonary
Sub Specialties: Pulmonary Fibrosis, Pulmonary
Recruitment Status: Recruiting

Contact Information

Scott Sweeten
scott.sweeten@hsc.utah.edu
801-581-5811

Brief Summary

This is an open label study that will be conducted in two parts. Together, Parts A and B will provide safety and efficacy data across the two GBT440 doses that are expected to improve oxygen saturation in the enrolled subjects.
Approximately up to 32 eligible subjects will be enrolled in the study.
• In Part A (Figure 1), up to approximately 16 eligible IPF subjects will receive 900 mg of GBT440 administered orally as 3 × 300 mg capsules or tablets once daily for 90 days.
• In Part B (Figure 1), up to approximately 16 eligible IPF subjects will receive 1500 mg of GBT440 administered orally as 5 × 300 mg capsules or tablets once daily for 90 days.
 
OBJECTIVES
Primary
To evaluate the effect of GBT440 on oxygen saturation at rest, breathing
room air, on Days 30 and 90 compared to baseline.
Secondary
• To evaluate the effect of GBT440 on the requirement for
supplemental O2 at rest and post-exercise at Days 30 and 90
compared to baseline
• To evaluate the effect of GBT440 on resting and post-exercise
Alveolar-arterial O2 tension difference [P(A-a)O2] at Days 30 and
90 compared to baseline
• To evaluate the effect of GBT440 on 6-minute walk distance
(6MWD) at Days 30 and 90 compared to baseline
• To evaluate the effect of GBT440 on IPF-related symptoms, using
patient reported outcomes (PROs), at Days 30 and 90 compared to
baseline
• To evaluate pulmonary function at Day 90 compared to baseline
• To evaluate the safety and tolerability of 900 mg and 1500 mg GBT440 dosed
daily for 90 days
• To evaluate the pharmacokinetics (PK) of GBT440
Exploratory
 To evaluate the effect of GBT440 on the need for any O2 while at
rest at Days 30 and 90 compared to baseline
• To compare the change in O2 requirement between the two O2 flow
rate allocation groups
• To evaluate the effect of GBT440 on extent of activity during daily
living at Days 30 and 90 compared to baseline

Inclusion Criteria

All subjects must meet all of the following inclusion criteria:
1. 45 to 85 years of age inclusive, at randomization
2. Able and willing to provide signed informed consent to participate in this study
3. Documented diagnosis of IPF, as indicated in the ATS/ERS/JRS/ALAT 2011 guidelines.
4. Receiving supplemental O2 for use at rest
 Subjects using O2 only with exercise will not be eligible
5.Resting oxygen saturation (SpO2) between 85 and 88% for at least 30 consecutive seconds
while breathing room air (refer to Section 5.1 and Section 5.5.2 for details regarding
confirming eligibility)
Or
Resting SpO2 <85% for 10 consecutive seconds or, if in the opinion of the site staff, it is
not safe or tolerable for the subject to continue without using their supplemental oxygen
for 10 consecutive seconds whilst the SpO2 is <85%.
Either of these 2 criteria should be met at both screening and Day 1 visits.
6. Able, in the Investigator's opinion, to walk a total of at least 100 meters at completion of the baseline 6-minute walk
test (6MWT)
7. Weight ≥ 40 kg
8. Able, in the Investigator’s opinion, to complete the O2 titration study unassisted at
baseline and Days 30, 90, and 120
9. Able, in the Investigator’s opinion, to comply with the study procedures, including
attending the assessment visits and adhering to study requirements and restrictions.
10. 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

Any subject who meets any one of the following criteria will be excluded from participation:
1. FEV1/FVC < 70%
2. History of interstitial lung diseases secondary to other medical conditions (e.g.,
scleroderma, sarcoidosis or rheumatoid arthritis) or resulting from clinically significant
environmental exposures including but not limited to, drug toxicity, hypersensitivity
pneumonitis, or asbestos.
3. Hospitalization due to an exacerbation of IPF within 30 days of screening
4. Documented pulmonary hypertension that is severe (WHO Functional Class IV) and/or
clinically unstable, as determined by the study Investigator
 Subjects with documented mild to moderate pulmonary hypertension on a
stable regimen of therapy for at least 3 months prior to screening will be
eligible for the study
5. Subject plans to begin, or has commenced, pulmonary rehabilitation within 30 days of
screening
 Subject who is on a stable exercise regimen at screening or whose regimen, in
the opinion of the Investigator, is not expected to change at any time during
the entire study will be considered eligible for the study
6. Corticosteroid therapy, for treatment of IPF, > 10 mg per day of prednisone (or an
equivalent), administered for 7 days or longer, within 30 days of screening.
 Subjects receiving a stable dose of ≤ 10 mg per day of prednisone (or an
equivalent) for at least 14 days prior to screening, and in the opinion of the
Investigator not anticipated to require a dose adjustment during the study, are
eligible for the study
7. Corticosteroid therapy for treatment of non-IPF diseases, unless:
 Receiving a stable dose of prednisone (or an equivalent) for at least 14 days
prior to screening, and in the opinion of the Investigator not anticipated to
require a dose adjustments during the study
8. 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).
9. AST, ALT or total bilirubin > 2 × ULN
10. Serum creatinine > 2.0 mg/dL
11. Clinical evidence of active infection, within 14 days of screening, which may include but
is not limited to bronchitis, pneumonia, urinary tract infection, or cellulitis.
12. Active viral hepatitis within the last 6 months
13. Active tuberculosis within the last 6 months
 Testing for latent tuberculosis is not required
14. ECG with a QTcF > 450 ms (males) or QTcF > 470 ms (females)
 If ventricular pacing is noted on ECG, then QTcF intervals will not be calculated
15. Family or personal history of congenital long QT syndrome
16. Female who is breast-feeding or pregnant
17. Known current malignancy or current evaluation for a potential malignancy or history of
malignancy within the past 2 years prior to screening, except for appropriately treated
non-melanoma skin carcinoma, carcinoma in situ of the cervix, Stage 1 uterine cancer
18. Current smoker (including use of eCigarettes or vaporizing) or history of smoking within 3 months from screening
19. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within
3 months of screening, including but not limited to, congestive heart failure requiring
hospitalization or uncontrolled clinically significant arrhythmias
20. History of mental illness within the last 5 years, unless the subject fulfills one of the
following conditions:
 The subject has not required or been prescribed any psychiatric medication
(including but not limited to antidepressants or anxiolytics) within 12 months
before screening and, in the opinion of the Investigator, the subject is able and
safe to participate in the study
 The subject has been on a fixed regimen of psychiatric medications for at least 6
months before screening and displays no sign of acute mental illness and, in the
opinion of the Investigator, the subject is able and safe to participate in the study
21. Other clinically significant medical disease that is uncontrolled despite treatment and is
likely, in the study Investigator’s opinion, to significantly impact the study’s efficacy and
safety assessments.
22. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)
23. Known hypersensitivity to any component of the study drug