Macitentan in the Treatment of Organ Rejection After Lung Transplantation

• Status: Withdrawn
• Trial end date: 2019-09-19
• Target enrollment: 0
• Participant gender: All

Summary

Potential therapy with MACITENTAN in the treatment of Chronic Lung Allograft Dysfunction (CLAD) after Lung Transplantation. Pilot Study, Double-blind, "ADD-ON Therapy" with MACITENTAN to "usual standard of care immunosuppressive therapies" after lung transplantation for established BOS Stages I or II versus a "matched control group" who receive "usual standard of care immunosuppressive therapies" alone, results in a decrease in the Primary Endpoint: "rate of decline" in "Forced Expiratory Volume-1 sec (FEV1) versus time" while Secondary Endpoints including: differences in Six minute walk distance (6MWD), BORG Score, corrected single-breath diffusing capacity (DCO corrected) at time intervals of 1, 3, 6 months on therapy. Specific biomarkers for BOS, including inflammatory chemokines, which are routinely collected in the context of post-transplant "surveillance" will be analyzed. Chemokines which our group has previously described in the pathogenesis of the continuum of "acute-to-chronic lung allograft rejection", have included both C-C (CCL2, CCL5) and CXC (CXCL9, CXCL10, CXCL11) chemokines as determined in bronchial-alveolar lavage (BAL).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Treatments: Macitentan

Criteria

Inclusion Criteria:

• UCLA unilateral or bilateral lung transplant recipients, ages: 21-65 years.

• Females of child bearing age who could become pregnant, must implement appropriate contraception per FDA requirement for "ERA medical treatment" with mandatory MONTHLY monitoring of urine or serum pregnancy tests.

• No concurrent clinically significant chronic liver disease

• Screening echocardiogram (performed as usual post-transplant standard of care) with LVEF>40%, only "Grade I" or less for "LV diastolic dysfunction".

• Non-intubated, fully ambulatory patients who can perform respiratory maneuvers for office Spirometry and DCO and 6MWD (no tracheostomy).

• Total of 20 patients with BOS Stage I or II, randomized double-blind to 'standard of care + placebo" versus "standard of care + MACITENTAN" Groups.

• Laboratory "safety studies" are already routinely monitored in the context of post-transplant patients' chronic immunosuppressive regimen and include: comprehensive metabolic panel, tacrolimus trough level, B-type natriuretic peptide (BNP), CBC + platelet count.

• "Physiologic" outcomes for this study are already considered "standard of care" for lung transplant recipients that include: Office-based Spirometry pre- and post-bronchodilator, corrected DCO, six minute walk distances + BORG score assessments (6MWD) at intervals of 1-3 months during routine Lung Transplant Clinic follow-up appointments.

Exclusion Criteria:

• UCLA unilateral or bilateral lung transplant recipients, ages: over 65 years of age.

• Females of child bearing age who could become pregnant, refuse to implement appropriate contraception per FDA requirement for "ERA medical treatment" with mandatory MONTHLY monitoring of urine or serum pregnancy tests or become pregnant.

• Concurrent clinically significant chronic liver disease

• Intubated patients

• Patients who cannot perform respiratory maneuvers for office Spirometry and DCO and 6MWD (no tracheostomy).