GBT4400-006

Principal Investigator: Mary  Scholand
Keywords: Pulmonary Fibrosis , Idiopathic Pulmonary Fibrosis , ILD , IPF Department: Pulmonary
IRB Number: 00090883 Co Investigator:  
Specialty: Pulmonary
Sub Specialties: Pulmonary Fibrosis
Recruitment Status: Not yet recruiting

Contact Information

Silvia Smith
silvia.smith@hsc.utah.edu
801-581-5811

Brief Summary

Primary
 To evaluate the safety and tolerability of multiple doses of GBT440 administered to subjects with IPF
 
Secondary
 
 To evaluate the effect of GBT440 on oxygen saturation at Days 15 and 28 compared to baseline during 6-minute walk testing (6MWT).
 To evaluate the pharmacokinetics (PK) parameters of GBT440 in plasma and whole blood. 
 
Exploratory
 To evaluate the effect of GBT440 on distance walked during the 6MWT at Days 15 and 28 compared to baseline.
 To evaluate the effect of GBT440 on IPF-related symptoms using patient reported outcomes (PROs) at Day 28 compared to baseline.
 To evaluate the effect of GBT440 on cardiopulmonary exercise testing (CPET) parameters at Day 29 compared to baseline.
 To evaluate pulmonary function, including assessment of spirometry and DLco at Day 28 compared to baseline
 To evaluate the PK-PD relationship of GBT440 at Days 15 and 28 compared to baseline.

Inclusion Criteria

1. Able and willing to provide signed informed consent to participate in
this study.
2. Documented diagnosis of IPF, as indicated in the ATS/ERS/JRS/ALAT 2011 guidelines.
3. Adult males or females aged 45-80 years inclusive at randomization
4. Oxygen saturation (SpO2) ≥ 88 % by pulse oximetry while breathing
room air at rest
5. Oxygen saturation (SpO2) < 88% and at least a 5% absolute decrease
during the baseline 6-minute walk test (6MWT) which is sustained for
at least 10 seconds
6. Able to walk at least 100 meters at completion of the baseline 6MWT
7. Weight ≥ 40 kg
8. Subject is seronegative for recent hepatitis A (IgM anti-HAV), hepatitis
B surface antigen (HBsAg), hepatitis C (HCV) antibody (anti-HCV),
and human immunodeficiency virus antibody (anti-HIV) within 3
months of screening.
9. Able, in the Investigator’s opinion, to complete the 6MWT unassisted
at baseline and Day 15 and Day 28 and comply with the study
procedures, including attending all assessment visits and adhering to all
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 3 months after
the last dose of study drug.

Exclusion Criteria

1. FEV1/FVC < 70%.
2. Requires supplemental oxygen therapy at rest.
3. History of other interstitial lung diseases including but not limited to
radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonia,
bronchiolitis obliterans, organizing pneumonia.
4. History of clinically significant environmental exposure known to
cause pulmonary fibrosis including but not limited to drugs (e.g.
methotrexate or amiodarone), asbestos, beryllium, radiation and
domestic birds.
5. History of other medical conditions that are known or may result in
interstitial lung disease. For example, any connective tissue disease
including but not limited to scleroderma,
polymyositis/dermatomyositis, systemic lupus erythematosus and
rheumatoid arthritis.
6. AST, ALT or total Bilirubin > 2 X ULN.
7.Creatinine Clearance (CrCl) < 30 mL/min/1.73 m2, calculated using the Modification of
Diet in Renal Disease estimated Glomerular Filtration Rate (MDRD eGFR)
8. Significant polycythemia defined as hemoglobin value > 18 mg/dL.
9. 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. If ventricular pacing is noted on ECG, then QTcF intervals
will not be calculated.
10. Family or personal history of congenital long QT syndrome.
11. Female who is breast-feeding or pregnant.
12. 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.
13. Subject has used any of the following therapies within 30 days of
screening:
 Any cytotoxic, immunosuppressive or cytokine-modulating
therapy including but not limited to: azathioprine, bosentan,
ambrisentan, cyclophosphamide, cyclosporine, etanercept,
iloprost, infliximab, leukotriene antagonists, methotrexate,
mycophenolate, tacrolimus
 Imatinib mesylate, Interferon gamma-1b, tyrosine kinase
inhibitors (excluding nintedanib)
14. Pulmonary hypertension requiring active therapy including but not
limited to endothelin receptor inhibitors or PDE inhibitors (e.g.,
sildenafil, tadalafil).
 Note: intermittent use of a PDE inhibitor for erectile dysfunction
may be allowed after approval by the Medical Monitor.
15. Hospitalization due to an exacerbation of IPF within 30 days of
screening
16. Subject plans to begin or has commenced pulmonary rehabilitation
within 30 days of screening
 Subjects 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
17. Corticosteroids (> 10 mg per day of prednisone or an equivalent)
within 30 days of screening.
18. Current smoker (including use of eCigarettes or vaporizing) or history of smoking within 3 months of screening.
19. Clinical evidence of active infection, including but not limited to
bronchitis, pneumonia, sinusitis, urinary tract infection or cellulitis,
within 14 days of screening
20. Active tuberculosis requiring treatment within the last 12 months
 Testing for latent tuberculosis is not required
21. Currently or, in the opinion of the investigator, soon to be listed for
lung transplant.
22. History of unstable or deteriorating cardiac or pulmonary disease (other
than IPF) within 6 months of screening including but not limited to the
following:
 Unstable angina pectoris or myocardial infarction or elective
coronary intervention
 Congestive heart failure requiring hospitalization
 Uncontrolled clinically significant arrhythmias
23. Any condition possibly affecting drug absorption, such as previous
surgery on the stomach or small intestine.
24. 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).
25. Known hypersensitivity to any component of the study drug.
26. Subject who, for any reason, is deemed by the investigator to be
inappropriate for this study; or has any condition (such as addictive or
psychosocial issues) which would confound or interfere with the
evaluation of the safety, tolerability, or PK of the investigational drug;
or is unable to comply with the study protocol.
27. 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