Macitentan in the Treatment of Organ Rejection After Lung Transplantation

NCT02893176 | Withdrawn Phase 4

• 1 other identifier: 14-001710
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Lung Transplant Rejection

Keywords

Lung Transplant; Macitentan; CLAD; BOS; bronchiolitis obliterans; chronic lung allograft dysfunction; Organ Rejection

Outcome Measures

Primary Outcomes (1)

• Measure of FEV1

  linearized slopes of loss of lung function (FEV1) / month

  Six Months on Therapy

Secondary Outcomes (4)

• Measure of FEV1

  One, Three, Six and Twelve Months

• Measure of Six Minute Walk

  One, Three, Six and Twelve Months

• Measure of Pulse Oximetry

  One, Three, Six and Twelve Months

• Measure of Diffusing Capacity

  One, Three, Six and Twelve Months

Other Outcomes (3)

• BNP Lab Values

  One, Three, Six and Twelve Months

• Creatinine Clearance Lab Values

  One, Three, Six and Twelve Months

• Serum Endothelin-1 Lab Values

  One, Three, Six and Twelve Months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

10mg will be administered one time daily

Drug: placebo (for macitentan)

Active

ACTIVE COMPARATOR

10mg macitentan will be administered one time daily

Drug: macitentan

Interventions

macitentan DRUG

Also known as: Opsumit

Active

placebo (for macitentan) DRUG

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of Califonia, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans

Interventions

macitentan

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Study Officials

• David J Ross, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: September 8, 2016
• Study Start: September 1, 2016
• Primary Completion: September 19, 2019
• Study Completion: September 19, 2019
• Last Updated: December 11, 2020

Record last verified: 2020-12

Locations

US (1)