A 26-Week, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Efficacy, Safety, and Tolerability of Axatilimab in Subjects with Idiopathic Pulmonary Fibrosis (IPF)
- Conditions
- Idiopathic pulmonary fibrosisMedDRA version: 21.1Level: PTClassification code: 10021240Term: Idiopathic pulmonary fibrosis Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- CTIS2022-502954-15-00
- Lead Sponsor
- Syndax Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 224
1.Male or female subject aged =40 years on the day of signing the Informed Consent Form (ICF)., 10. Subject is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol., 11. Subject and Investigator considered all medicinal treatment options and/or possibly lung transplantation prior to considering participation in the study., 2. Documented diagnosis of IPF per the 2018 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society Clinical Practice Guideline (Raghu 2018)., 3. HRCT confirming the diagnosis of IPF based on radiographic findings, as follows: Chest HRCT performed within 12 months prior to Screening Visit 1 and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT only (if no lung biopsy is available) or based on both HRCT and lung biopsy (with application of the different criteria in either situation). If an evaluable HRCT <12 months prior to Screening is not available, an HRCT can be performed at Screening Visit 1 to determine eligibility, according to the same requirements as the historical HRCT. If a subject has an indeterminate usual interstitial pneumonia (UIP) pattern and their HRCT is >6 months old, if in the opinion of the Investigator their disease has progressed, an additional HRCT may be obtained and reviewed for eligibility., 4. Subjects are eligible if they meet either of the following criteria: a. UIP or probable UIP pattern determined by at least 2 reviewers (see Appendix 3), or b. Indeterminate UIP with an accompanying biopsy supporting UIP or probable UIP histopathology pattern. The pathology report from a locally certified pathologist will provide documentation of histopathologic criteria (see Appendix 3)., 5. Meeting one of the following criteria for background IPF medication use: a.Subjects may be treatment-naïve to nintedanib or pirfenidone for reasons such as contraindication to nintedanib or pirfenidone or subject refusal. (Note: Initiation of nintedanib or pirfenidone and consideration of other therapies for IPF should be discussed by Investigator before study enrollment.) b.Subjects receiving pirfenidone or nintedanib for IPF must have been at a stable dose for at least 12 weeks before Screening. c.If subjects have previously taken and discontinued nintedanib or pirfenidone for any reason (eg, side effect, no therapeutic benefit, refusal of these medications by the subject), they must have discontinued such treatment =4 weeks prior to Screening Visit 1. Note: Discontinuation of nintedanib or pirfenidone for the sole purpose of enrollment in this study is not allowed., 6. Meeting all of the following criteria during the Screening Period: a. FVC =45% of predicted normal at Screening Visit 1 or Visit 2, b. Forced expiratory volume in 1 second (FEV1)/FVC =0.7 at Screening Visit 1 or Visit 2, c. DLCO =30% and =90% of predicted, corrected for hemoglobin at Screening Visit 1, d. Acceptability: Subject can perform acceptable PFTs (ie, meet ATS/ERS acceptability criteria [Appendix 2] at Screening Visits 1, 2, and 3). e. Repeatability: Subject can perform technically acceptable PFTs meeting repeatability criteria for FVC at Screening Visits 1, 2, and 3 (Appendix 2)., 7. Estimated minimum life expectancy of at least 12 months for non-IPF-related disease in the opinion of the Investigator., 8. Male s
1. History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer that has been medically managed through active surveillance or watchful waiting, squamous cell carcinoma of the skin if fully resected, non-invasive ductal carcinoma in situ of the breast, and melanoma in situ)., 10. Acute respiratory or systemic bacterial, viral, or fungal infection requiring systemic treatment either during Screening or prior to Screening and not successfully resolved 4 weeks prior to Screening Visit 1., 11. Class IV New York Heart Association chronic heart failure., 12. Significant pulmonary hypertension (PH) defined by any of the following: a. Previous clinical or echocardiographic evidence of significant right heart failure b. History of right heart catheterization showing a cardiac index =2 L/min/m² c. PH requiring parenteral therapy with epoprostenol/treprostinil, 13. Cardiopulmonary rehabilitation program based on exercise training that has been completed within 6 weeks prior to Screening or planned to start within the first 6 weeks of the subject's enrollment in this study., 14. History of cigarette smoking or vaping within the previous 3 months., 15. Recent history (<6 months) of alcohol or substance abuse disorder., 16. Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to Screening or during the Screening Period (eg, acute coronary disease, heart failure, and stroke)., 17. Major surgery within 3 months prior to Screening, during screening or have major surgery planned during the study period., 18. Alanine aminotransferase and/or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN) or total bilirubin =1.5 x ULN. Retesting is allowed once., 19. Moderate to severe hepatic impairment (Child-Pugh B or C)., 2. Abnormalities detected on ECG of either rhythm or conduction that in the opinion of the Investigator are clinically significant. Note: • Subjects with implantable cardiovascular devices (eg, pacemaker) affecting the QT interval time may be enrolled in the study based upon Investigator judgment following cardiologist consultation if deemed necessary. • Atrial fibrillation that has been clinically stable for at least 6 months and that has been appropriately treated with anticoagulants and controlled with a rate control strategy (eg, selective beta blocker, calcium channel blocker, digoxin or ablation therapy) for at least 6 months is allowed for inclusion. In such subjects, if atrial fibrillation is present at Visit 1, resting ventricular rate must be <100 beats per minute., 20. Amylase or lipase >1.5 x ULN; creatine phosphokinase (CPK) >2 x ULN. Retesting is allowed once., 21. Abnormal renal function defined as estimated creatinine clearance of <30 mL/min, calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula (Inker 2021). Retesting is allowed once., 22. History of acute pancreatitis in the prior 12 months or =2 episodes in past 3 years., 23. Subject with acquired immune deficiency syndrome., 24. A history of tuberculosis in the prior 6 months, or subjects with active or latent tuberculosis, confirmed by a positive test during Screening (interferon gamma release assay). [The interferon gamma release assay may be substituted with local tuberculosis test or local tuberculosis test results determined within 6 months prior to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effect of axatilimab compared to placebo on lung function in subjects with IPF from baseline to Week 26;Secondary Objective: To assess the effect of axatilimab compared to placebo on disease progression from baseline to Week 26, To assess the effect of axatilimab compared to placebo on change in additional parameters of lung function from baseline to Week 26, To assess the effect of axatilimab compared to placebo in quality-of-life measures from baseline to Week 26, To assess the effect of axatilimab compared to placebo on gas exchange from baseline to Week 26;Primary end point(s): The annualized rate of decline in morning pre dose trough forced vital capacity (FVC) (mL) over 26 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Time to disease progression. Disease progression is defined as absolute FVC percent predicted decline of =10%, or occurrence of lung transplant or all-cause death prior to Week 26.;Secondary end point(s):The annualized rate of decline in FVC percent predicted over 26 weeks.;Secondary end point(s):Change in St. George’s Respiratory Questionnaire (SGRQ) from baseline to Week 26.;Secondary end point(s):The mean change in diffusion capacity for carbon monoxide (DLCO % of predicted, corrected for hemoglobin) from baseline to Week 26.