Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: ACT-064992 (macitentan); Placebo
Intervention description: ACT-064992 (macitentan) tablet, 10 mg, once daily; matching placebo, once daily
Intervention MeSH terms: Macitentan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 178.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: idiopathic pulmonary fibrosis; MUSIC

Summary:

      The AC-055B201/MUSIC study is a Phase II study, comparing one dose of ACT-064922 (macitentan)
      10 mg with 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 idiopathic pulmonary fibrosis (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.
    

Eligibility criteria:

        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 American
             Thoracic Society/European Respiratory Society 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: forced vital capacity (FVC) < 50% predicted, or FVC <
             1.2 liter.

          5. Diffusing capacity of the lung for carbon monoxide (DLCO) < 30% predicted.

          6. Residual volume ≥ 120% predicted.

          7. Obstructive lung disease: forced expiratory volume in 1 second (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., pulmonary function tests).

         11. Chronic heart failure with New York Heart Association 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. Aspartate aminotransferase (AST) and/or alanine aminotransferase > 1.5 x upper limit
             of normal.

         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, tumor
                  necrosis factor α blockers, imatinib and interferon γ,

               -  Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day).

               -  Oral anticoagulants prescribed for IPF.

         20. Treatment with endothelin receptor antagonists within 4 weeks prior to randomization.

         21. Systemic treatment within 4 weeks prior to randomization with cyclosporine A or
             tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR)
             inhibitors).

         22. Treatment with Cytochrome P450 3A 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.