A study to evaluate if a new drug is effective in preventing the progression of lung fibrosis

• Register: EUCTR
• Last refreshed on: 18 January 2016
• Main ID: EUCTR2012-001571-36-DE
• Date of registration: 02/04/2013
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A study to evaluate if a new drug is effective in preventing the progression of lung fibrosis
• Scientific title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of GS-6624 in Subjects with Idiopathic Pulmonary Fibrosis (RAINIER). - RAINIER
• Date of first enrolment: 17/06/2013
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001571-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, Germany, Israel, Italy, Korea, Republic of, Poland, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences Inc.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects from 45 to 85 years of age
2. A confident diagnosis of IPF consistent with diagnostic criteria described in the 2011 American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. HRCT or surgical lung biopsy data will be interpreted by a central service. The term “surgical lung biopsy” encompasses biopsies obtained at open thoracotomy and thoracoscopy, as well as, cryobiopsies obtained through bronchcoscopy. The diagnosis of IPF must have been made within 3 years prior to screening, or if diagnosis was made > 3 years prior to screening, there must be evidence of clinical worsening within 12 months prior to screening, as judged by the investigator.
3. 6MWD = 50 meters (164 feet): use of = 6 L/min supplemental O2 is permitted 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 a 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 90 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 ß 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 investigational medicinal product (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 ICF prior to the initiation of any study procedures/assessments, unless it is performed as standard of care for this disease.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 375

Exclusion criteria:
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 prebronchodilator value
OR
• FEV1/FVC ratio < age adjusted lower limit of normal (LLN)
OR
• Residual volume (RV) > 120% by plethysmography (see Section 6.5 for alternative methods)
OR
• Significant emphysema on HRCT defined as more emphysema than fibrosis interpreted by a central radiology service
4. FVC > 90%
5. Hemoglobin corrected, not volume corrected, DLCO <25% of predicted normal
6. Surgical lung biopsy diagnostic for pneumoconiosis, hypersensitivity pneumonitis nonspecific interstitial pneumonia or other idiopathic interstitial lung disease
7. Any clinically diagnosed collagen vascular disease
8. History of aortic aneurysm = 3.5cm in diameter
9. History of cerebrovascular accident (stroke) within the preceding 26 weeks
10. 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
11. Require pharmaceutical treatment for pulmonary hypertension
12. Hospitalization for acute respiratory illness < 26 weeks prior to screening, unless reviewed with the Medical Monitor
13. Aspiration pneumonia < 26 weeks prior to screening
14. Active or recent (< 4 weeks prior to Screening and/or during the screening period) respiratory bacterial, viral, fungal, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement)
15. Active work-up for suspected lung cancer or history of cancer or precancerous state (eg, familial polyposis, BRCA1, BRCA2, carcinoma in-situ) within 5 years prior to screening except for the following:
• Definitive prophylactic surgery for precancerous state
• Excision of non melanomatous skin cancer treated with clear margins
• Prostate carcinoma treated with surgery or radiation with normal PSA for 24 months, not requiring either chemotherapy or hormone therapy
16. 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)
17. Co-morbid condition or illness limiting life expectancy to < 2 years at time of screening
18. Major surgery, as defined by the investigator, < 30 days prior to screening or scheduled major elective surgery during the expected duration of the study
19. 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
20. Current excessive consumption of alcohol or use of illegal drugs as determined by the investigator
Related to physiologi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Idiopathic pulmonary fibrosis
MedDRA version: 18.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Code: GS-6624
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Simtuzumab
CAS Number: 1318075-13-6
Current Sponsor code: GS-6624
Other descriptive name: GS-6624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective of this study is:

To determine the effect of simtuzumab (GS-6624) on progression free survival (PFS) as determined by either a categorical decline in forced vital capacity (FVC) and 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.

Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated at every visit from randomisation onwards

Primary end point(s): PFS among intent-to-treat (ITT) subjects. PFS is defined as time between randomization and all-cause mortality or a categorical decrease in FVC % predicted (= 10% relative decrease and a = 5% absolute decrease) from baseline.

PFS in a subset of ITT subjects who are classified as LOXL2 High based on a pre-specified threshold level of LOXL2 in serum at baseline

Secondary Objective: • Effects of simtuzumab on all-cause mortality
• Predictive effects of baseline serum LOXL2 levels on treatment response as measured by primary and secondary endpoints
• Effects of simtuzumab on change in lung function
• Effects of simtuzumab on adjudicated acute exacerbations
• Effects of simtuzumab on adjudicated respiratory hospitalizations and adjudicated deaths
• Effects of simtuzumab on 6-minute walk distance (6MWD)
• Effects of simtuzumab on quality of life
• The safety and tolerability of simtuzumab
• Exploratory objectives include evaluation of:
• Effect of simtuzumab on degree of fibrosis on high resolution computed tomography (HRCT) scans
• Effect of simtuzumab on sLOXL2 levels compared to placebo
• Prognostic effects of baseline levels of sLOXL2 on disease prognosis as determined in placebo arm.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints are:
• All-cause mortality as measured by overall survival among ITT subjects
• All-cause mortality among subjects who are sLOXL2 High at baseline
Exploratory endpoints are:
• Adjudicated acute exacerbations
• Adjudicated respiratory hospitalizations
• Change in FVC % predicted
• Change in DLCO % predicted
• Absolute change in 6MWD
• Change in SGRQ score
• Change in HRCT findings since baseline
• Change in sLOXL2 levels
• Determine whether baseline sLOXL2 levels are prognostic for disease progression in placebo arm of the study
• Evaluate the predictive effects of baseline sLOXL2 levels on various clinical endpoints as outlined in secondary objectives

Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated at every visit from randomisation onwards.

PK trough serum simtuzumab levels will be measured approximately every 12 weeks.

Secondary ID(s)

2012-001571-36-IT

GS-US-322-0207

Source(s) of Monetary Support

Gilead Sciences Inc.