Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study (MUSIC)

The AC-055B201/MUSIC study is a Phase II study, comparing one dose of macitentan (10 mg) vs placebo in patients with idiopathic pulmonary fibrosis (IPF). The main study objective is to demonstrate that macitentan positively affects the forced vital capacity (FVC) in comparison with placebo in patients with IPF.

The secondary objectives are to evaluate the effect of macitentan on the time to disease worsening or death in patients with IPF, and to evaluate the benefit/risk profile of macitentan in the treatment of patients with IPF.

• Drug: ACT-064992 (macitentan)
  tablet, 10 mg, once daily
  Other Name: macitentan
• Drug: Placebo
  matching placebo, once daily

• Experimental: 1
  ACT-064922 tablet, 10 mg, once daily
  Intervention: Drug: ACT-064992 (macitentan)
• Placebo Comparator: 2
  Matching placebo, one daily
  Intervention: Drug: Placebo

Inclusion Criteria:

1. Signed informed consent.
2. Male or female patients of at least 18 years of age (females of child-bearing potential must use a reliable method of contraception).
3. IPF diagnosis within 3 years prior to randomization, proven according to the ATS/ERS consensus conference criteria, with surgical lung biopsy.

Exclusion Criteria:

1. Interstitial lung disease due to conditions other than IPF.
2. Presence of extensive honeycombing on Baseline high-resolution computed tomography (HRCT) scan performed within 3 months prior to randomization.
3. Severe concomitant illness limiting life expectancy (< 1 year).
4. Severe restrictive lung disease: FVC < 50% predicted, or FVC < 1.2 liter.
5. DLCO < 30% predicted.
6. Residual volume ≥ 120% predicted.
7. Obstructive lung disease: FEV1/FVC) < 0.70.
8. Documented sustained improvement of the patient's IPF condition up to 12 months prior to randomization with or without IPF-specific therapy.
9. Recent pulmonary or upper respiratory tract infection (up to 4 weeks prior to randomization).
10. Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., PFTs).
11. Chronic heart failure with NYHA class III/IV or known left ventricular ejection fraction < 25%.
12. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
13. Estimated creatinine clearance < 30 mL/min.
14. AST and/or ALT > 1.5 x ULN.
15. Hemoglobin < 75% of the lower limit of the normal range.
16. Systolic blood pressure < 100 mmHg.
17. Pregnant or breast-feeding.
18. Current drug or alcohol dependence.

19. Chronic treatment with the following drugs (within 4 weeks of randomization):

    • Oral corticosteroids (> 20 mg/day of prednisone or equivalent),
    • Immunosuppressive or cytotoxic drugs including cyclophosphamide and azathioprine,
    • Antifibrotic drugs including pirfenidone, D penicillamine, colchicine, TNFα blocker, imatinib and interferon γ,
    • Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day).
    • Oral anticoagulants prescribed for IPF.
20. Treatment with ERAs within 4 weeks prior to randomization.
21. Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors).
22. Treatment with CYP3A inducers within 4 weeks prior to randomization.
23. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
24. Planned treatment, or treatment with another investigational drug within 4 weeks prior to randomization.