RAINER

Overview

Status: Recruiting
Keywords: IPF , Idiopathic Pulmonary Fibrosis , Lung Disease
IRB Number: 00062107
Specialty: Pulmonary, Pulmonary, Pulmonary, Pulmonary
Sub Specialties: Pulmonary Rehabilitation, Pulmonary Fibrosis, Pulmonary Function,

Brief Summary

The primary objective of this study is:

To determine the effect of GS-6624 on progression free survival(PFS) as determined by either a categorical decline in forced vital capacity (FVC) or all-cause mortality, in all subjects enrolled or in a subset of subjects who are classified as Lysyl Oxidase-like-2 (LOXL2) High based on a pre-specified level in serum at baseline.

  • Secondary objectives include evaluation of:
  • Effects of GS-6624 on all-cause mortality
  • Predictive effects of baseline serum lysyl oxidase like 2
  • (sLOXL2) levels
  • Effects of GS-6624 on change in lung function
  • Effects of GS-6624 on adjudicated acute exacerbations
  • Effects of GS-6624 on adjudicated respiratory hospitalizations
  • Effects of GS-6624 on 6-minute walk distance (6MWD)
  • Effects of GS-6624 on quality of life
  • The safety and tolerability of GS-6624
  • Exploratory objectives include evaluation of:
  • Effect of GS-6624 on degree of fibrosis on high resolution
  • computed tomography (HRCT) scans
  • Effect of GS-6624 on sLOXL2 levels compared to placebo
  • Prognostic effect of baseline sLOXL2 on primary and
  • secondary objectives (among placebo treated subjects only)
  • Predictive effect of baseline sLOXL2 on the secondary
  • objectives and subsequent sLOXL2 levels

Principal Investigator: Mary Scholand
Department: Pulmonary
Co Investigator:

Contact Information

Name:Patrick Carey
Phone: 801-581-5864
Email: patrick.carey@hsc.utah.edu

Inclusion Criteria

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in

this study.

1. Male or female subjects from 45 to 85 years of age

2. A confident diagnosis of IPF consistent with dagnostic criteria described in the 2011 ATS/ERS Consensus Statement. HRCT or

surgical lung biopsy (SLB) will be interpreted by a central service.  

3. 6MWD 50 meters (164 feet): use of 6 L/min supplemental O2 is required for all

subjects

4.Able to maintain O2 saturation of ≥ 89% while breathing room air at rest at sea level. If

the study site is located at more than 1000 meters above sea level, the subject must be
able to maintain O2 saturation of ≥ 89% while on 2 liters of supplemental oxygen at rest
(eligible subjects are permitted to use supplemental oxygen during sleep and on exertion
based on the clinical judgment of the investigator, to a maximum of 6 liters/minute)

5. Able to perform complete breath hold for diffusing lung capacity so that carbon monoxide (DLCO) measurement can be safely undertaken

6. Negative serum pregnancy test at screening and negative urine pregnancy test at

randomization for female subjects of childbearing potential

7. Willingness of female subjects of childbearing potential to undergo urine pregnancy tests at each study visit starting at randomization 

8. Females of childbearing potential must agree to use highly effective methods of

contraception from the Screening visit throughout the study period and for 30 days

following the last dose of IMP. Please refer to Section 8.11.2 for protocol recommended

methods of contraception; females of childbearing potential must have negative serum

β-hCG at Screening

9. Non-vasectomized male subjects must agree to use a highly effective method of

contraception if sexually active with a partner who is of child bearing potential.  Subjects must refrain from sperm donation from randomization throughout the study period until 90 days following the last dose of IMP

10. Lactating females must agree to discontinue nursing before enrolling in the study and for

the duration of the study while receiving IMP.

11. Competency to understand the information given in the Institutional Review Board (IRB)

or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF);

subjects must sign the form prior to the initiation of any study procedures, unless the

assessment is performed as standard of care for this disease.

 

Exclusion Criteria

Exclusion Criteria

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

1. Pregnant or breastfeeding

2. Clinically significant respiratory diseases other than IPF, including asbestosis, other

pneumoconiosis or hypersensitivity pneumonitis

3. Obstructive lung disease determined by Pulmonary Function Test (PFTs) or HRCT as

follows:

Evidence of reactive airway disease by an increase in forced expiratory volume in

1 second (FEV1) following bronchodilator challenge that exceeds both 200 ml AND
exceeds a 12% increase from the pre-bronchodilator value

OR

FEV1/FVC ratio < age adjusted lower limit of normal (LLN)

OR

Residual volume (RV) > 120% by plethysmography

OR

significant emphysema on HRCT defined as more emphysema than fibrosis interpreted by a central radiology

service

4. FVC >90%

4. Hemoglobin corrected, not volume corrected, (DLCO) <25% of predicted normal

5. Surgical lung biopsy (SLB) showing, pneumoconiosis, hypersensitivity pneumonitis

nonspecific pneumonia or other idiopathic interstitial lung disease

6. Any collagen vascular disease

7. History of aortic aneurysm 3.5cm in diameter

8. History of cerebrovascular accident (stroke) within the preceding 26 weeks

9. Clinically significant heart disease defined as a myocardial infarction documented by an

ST elevation (STEMI) on electrocardiogram (ECG) within 6 months prior to screening,

percutaneous coronary intervention or coronary artery bypass surgery within 6 months

prior to screening, unstable angina pectoris, congestive heart failure (NYHA class III/IV

or known left ventricular ejection fraction < 25%), right heart failure, significant right

ventricular hypertrophy, or uncontrolled arrhythmia

10. Require pharmaceutical treatment for pulmonary hypertension

11. Hospitalization for acute respiratory illness < 26 weeks prior to screening

12. Aspiration pneumonia < 26 weeks prior to screening

13. Active or recent (< 4 weeks prior to enrollment) respiratory bacterial, viral, fungal, or

other infection (defined as exhibiting ongoing signs/symptoms related to the infection

and without improvement)

14. Active work-up for suspected lung cancer or history of cancer or precancerous state (eg, familial polyposis, BRCA1, BRCA2), within 5 years prior to screening except for the following:

-Definitive prophylactic surgery for precancerous state

-Excision of non malanomatous skin cancer trated with clear margins

-Prostate carcinoma treated with surgery or radiation with normal PSA for 24 months, not require either chemotherapy or hormone therapy.

15. History of human immunodeficiency virus (HIV), or active hepatitis C, or hepatitis B infection.  Subjects with hepatitis C who have had successful curative therapy will be eligible

16. Co-morbid condition or illness limiting life expectancy to < 2 years at time of screening

17. Major surgery, as defined by the investigator, < 30 days prior to screening or scheduled

elective surgery during the expected duration of the study

18. History or evidence of a clinically significant disorder, condition, or disease that, in the

opinion of the investigator and the Gilead medical monitor, would pose a risk to subject

safety or interfere with the study evaluations, procedures, or completion

19. Current excessive consumption of alcohol or use of illegal drugs as determined by the

investigator

Related to physiologic or organ specific abnormalities:

20. Use of supplemental O2 > 6L/min during activity

21. Inadequate organ function reflected by any of the following:

Platelets < 100 x 109/L

Hemoglobin < 11.0 g/dL

Absolute Neutrophil Count (ANC) < 1.5 x 109/L

PT/INR and PTT > 1.5 x upper limit of normal (ULN)

AST/ALT > 3 x ULN

Total bilirubin > 1.5 x ULN

Serum creatinine > 2.0 mg/dL

Related to treatment for IPF or investigational drugs:

22. Treatment with immunosuppressive, cytotoxic, or antifibrotic drugs including colchicine, cyclosporine A, TNF-α antagonists, tyrosine kinase inhibitor,

interferon-gamma, cyclophosphamide, or azathioprine < 28 days prior to randomization

are not permitted

N-acetylcysteine is permitted provided the subject has been on stable dose for> 4 weeks prior to screening.

• .Concomitant use of pirfenidone or nintedanib must be in accordance with the

approved prescribing instructions in the country where the site is located.

23. Oral doses of corticosteroids exceeding the equivalent of 10 mg prednisone per day within the 60 days prior to Screening and/or the during the screening period. 

24. Participation in an investigational drug or device trial < 30 days prior to screening or

within 5 times the half-life of the investigational agent in the other clinical study, if

known

25. Treatment with GS-6624 in another clinical study

26. Listed as active on a lung transplant waiting list.However subjects at transplant centers with long waiting times (greater than 1 year) may be permitted to enter the study after discussion with Medical Monitor to ensure that subjects will not undergo transplant surgery while on study drug.