ARTEMIS: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group, Event-Driven Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects with Early Idiopathic Pulmonary Fibrosis (IPF).
- Conditions
- Idiopathic Pulmonary Fibrosislung fibrosis10024967
- Registration Number
- NL-OMON35478
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 6
1. Male or females from 40 to 80 years of age
2. Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on the following criteria in accordance with ATS-ERS guidelines for diagnosing IPF:
* Definite or probable UIP confirmed on SLB by core pathologist
or
* In absence of SLB, HRCT scan showing definite findings for IPF (bibasilar reticular abnormalities with minimal ground glass opacities) as determined by core review
and three of the following *minor criteria*:
* Age > 50 years
* Insidious onset of otherwise unexplained dyspnea on exertion
* Duration of illness >= 3 months
* Bibasilar, inspiratory crackles
Within 90 days of study enrollment, diagnosis must be confirmed by HRCT
3. Honeycombing <= 5% as assessed on HRCT; HRCT results will undergo a core review process (Section 7.4) to confirm diagnosis.
4. Willingness to undergo RHC at baseline and at Visit 7 or end of study (EOS)
5. Willingness and ability to comply with required monitoring of liver function every 28 days. LFTs include serum ALT, AST, alkaline phosphatase, gamma glutamyl transferase (GGT), and total bilirubin concentrations
1. Chronic treatment with the following drugs prescribed for IPF (within 4 weeks of randomization):oral corticosteroids (> 20 mg/day of prednisone or equivalent), immunosuppressive or cytotoxic drugs, antifibrotic drugs, chronic use of N-acetylcysteine (prescribed for IPF)
2. Chronic treatment with immunosuppressive, cytotoxic, or antifibrotic drugs including pirfenidone, D penicillamine, colchicine, TNF a antagonists, imatinib, interferon gamma, cyclophosphamide, cyclosporine A, or azathioprine within 30 days of randomization (Section 5.4)
3. Obstructive lung disease as determined by evidence of airflow obstruction on HRCT or physiologic criteria including:
• FEV1/FVC ratio < 0.7
• RV > 120% by plethysmography or significant (verified by radiologist) emphysema on HRCT if plethysmography not available
• Evidence of reactive airway disease by change in FEV1 of > 12% following bronchodilator challenge
4. Active or recent (<= 60 days prior to enrollment) pulmonary or upper respiratory tract infection
5. Hospitalization within 60 days of screening for an acute exacerbation of IPF
(AE IPF)
6. Chronic heart failure (NYHA class III/IV) or known left ventricular ejection fraction <25%
7. Acute or chronic impairment (other than dyspnea) which limits the ability to comply with study requirements and procedures including the 6 min-walk test.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of this study is as follows:<br /><br>Time to death or disease progression, defined as the first occurrence of any of<br /><br>the following:<br /><br>• Either a decrease of >= 10% in FVC (L) and a decrease of >= 5% in diffuse lung<br /><br>capacity for carbon monoxide (DLCO) (ml/min/mmHg) or a decrease of >= 5% in FVC<br /><br>(L) and a decrease of >= 15% in DLCO (ml/min/mmHg); (deterioration in FVC and<br /><br>DLCO must be confirmed at the subsequent visit within 28 (± 14) days)<br /><br>• Respiratory hospitalization (as defined in Section 7.10). Events will be<br /><br>adjudicated by a blinded Endpoint Committee<br /><br>• All cause mortality. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints of this study are as follows:<br /><br>• Proportion of subjects with disease progression or death at 48 weeks (Visit 7)<br /><br>• Change in pulmonary function tests (FVC and DLCO) at Visit 7<br /><br>• Change in 6 minute walk distance (6MWD) at Visit 7<br /><br>• Change in QOL score at Visit 7 as assessed by:<br /><br>o Short Form 36® (SF 36)<br /><br>o St. George*s Respiratory Questionnaire (SGRQ)<br /><br>• Change in dyspnea as assessed by change in Transition Dyspnea Index (TDI)<br /><br>score at Visit 7<br /><br>• Among subjects without PH at baseline, the proportion who develop PH on study<br /><br>(documented by RHC)</p><br>