| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Idiopathic Pulmonary Fibrosis (IPF) |
|
| E.1.1.1 | Medical condition in easily understood language |
IPF is a chronic condition in which the lungs become scarred causing low oxygen levels in the blood and worsening breathlessness. It is not clear what causes it and there is no known cure.
|
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10021240 |
| E.1.2 | Term | Idiopathic pulmonary fibrosis |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the effect of GBT440 on oxygen saturation at rest, breathing room air, on Days 30 and 90 compared to baseline. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of GBT440 on the requirement for supplemental oxygen (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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 American Thoracic
Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Respiratory Society (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 on 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 (Day 1) 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 childbearing potential willing and able to use highly effective methods of contraception from study start to 30 days after the last dose of study drug |
|
| E.4 | Principal exclusion criteria |
1) Forced expiratory volume in 1 second (FEV1) / forced vital capacity (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 (World Health Organization [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 the 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 adjustment 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) Aspartate aminotransferase (AST), alanine aminotransferase (ALT)
or total bilirubin >2 × upper limit of normal (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) Electrocardiogram (ECG) with a corrected QT interval using the Fridericia formula (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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is change and % change from baseline in oxygen saturation at rest (SpO2 or SaO2), measured while breathing room air. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Change and % change from baseline in O2 flow rate (L/min), measured at rest, to maintain a target oxygen saturation (SpO2) of 89 to 92%, at Days 30 and 90.
• Change and % change from baseline in O2 flow rate (L/min), measured post-exercise to maintain a target oxygen saturation (SpO2 or SaO2) of 89 to 92%, at Days 30 and 90
• Change and % change from baseline in resting P(A-a) O2 at Days 30 and 90
• Change and % change from baseline in post-exercise P(A-a) O2 at Days 30 and 90
• Change and % change from baseline in 6MWD, at Days 30 and 90
• Change in patient-reported IPF-related symptoms from baseline, measured by ATAQ and SGRQ, at Days 30 and 90
• Change from baseline in FVC and DLco at Day 90 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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