Evaluating ARINA-1 for preventing lung transplant complications

A Phase 3, Open-label, Randomized, Standard of Care-controlled, Parallel Study Arm Study to Demonstrate Efficacy and Safety of ARINA-1 in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) Progression in Participants With a Bilateral Lung Transplant

This study is testing if a new treatment called ARINA-1 can help prevent lung transplant complications in people who have received a bilateral lung transplant.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Renovion, Inc. (Industry-sponsored)
• Drugs / interventions: alemtuzumab
• Locations: 20 sites (Phoenix, Arizona and 19 other locations)
• Trial ID: NCT05654922 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial aims to assess the effectiveness of ARINA-1, a nebulized immunomodulatory agent, in preventing the progression of bronchiolitis obliterans syndrome (BOS) in patients who have undergone bilateral lung transplants. Participants will receive either ARINA-1 in addition to standard care or standard care alone, with evaluations occurring at multiple clinic visits over 48 weeks. The study will also monitor quality of life and the need for increased immunosuppression. Telehealth visits and phone calls will be used to track adverse events and provide patient education.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 who have had a bilateral lung transplant for over 12 months and are experiencing a decline in lung function.

Not a fit: Patients who are not experiencing a decline in lung function or who have not had a lung transplant are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life and health outcomes for lung transplant recipients at risk of BOS.

How similar studies have performed: While this approach is novel in the context of ARINA-1 for BOS, similar immunomodulatory treatments have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. Bilateral lung transplant \>12 months from the time of Visit 1 / Randomization
2. Age 18-75 years old at the time of consent
3. Routinely followed at enrolling site
4. Willing and able to comply with visit schedule and at-home requirements
5. 10-24% decrease in FEV1 from the post-transplant baseline within the last 12 months.
6. Capable of giving informed consent
7. On a stable maintenance regimen of azithromycin for \>4 weeks prior to the Screening Visit
8. On a stable 2-agent or 3-agent immunosuppression regimen that includes a steroid, a calcineurin inhibitor (CNI), and, optionally, a cell cycle inhibitor (e.g., mycophenolate, azathioprine) \>4 weeks prior to Screening
9. If a woman of childbearing potential (WOCBP), must agree to use a reliable method of birth control for the entire duration of the study.

Exclusion Criteria:

1. Positive urine pregnancy test at screening and baseline visit
2. Diagnosis of active congestive heart failure or symptomatic coronary artery disease \> grade 3 based on the New York Heart Association Functional Classification (NYHA) criteria
3. Restrictive allograft syndrome (RAS) defined by radiographic interstitial or alveolar opacities on chest X-ray or CT scan that are consistent with RAS
4. Have advanced BOS, defined by \>24% decrease in FEV1 in post-transplant baseline
5. A diagnosis of probable antibody-mediated rejection (AMR) \<12 months prior to the baseline visit
6. Donor-specific antibodies (DSA) identified \<6 months prior to the baseline visit. \*The presence of DSA \>6 months from the baseline visit is acceptable for enrollment into the study.
7. Unresolved diffuse alveolar damage
8. Receiving mechanical ventilation
9. Chronic kidney disease stage IV or higher, including on dialysis
10. Initiating a new maintenance therapy or changing immunosuppression maintenance therapy (e.g., changing tacrolimus to cyclosporine) \<30 days prior to the baseline visit.
11. Have initiated or changed mTOR maintenance therapy \<3 months prior to Clinic Visit 1 (mTOR use for \>3 months is allowed)
12. Initiating or changing antibiotic (including azithromycin), antiviral, or antifungal therapy \<14 days prior to the baseline visit.
13. Use of alemtuzumab \<6 months prior to the baseline visit
14. Use of anti-thymocyte therapies (e.g., anti-thymocyte globulin) or photopheresis \<90 days prior to the Screening Visit. Prior use of Trikafta (elexacaftor, ivacaftor, and tezacaftor is allowed as long as the participant has been on stable dose for \>90 days prior to the Screening Visit.
15. Initiating a multivitamin or other supplement (inhaled, oral, or IV) containing vitamin C, glutathione, or N-acetylcysteine \<90 days prior to the baseline visit
16. Significant unstable comorbidities, in the opinion of the site investigator
17. Allery or previous adverse reaction to azithromycin
18. A diagnosis of dynamic collapse / tracheobrochomalacia \<90 days of the baseline visit.
19. Subjects currently participating in, or who have participated in an interventional (drug or device) clinical study \<30 days of the baseline visit.
20. Have been diagnosed with ARAD within 6 weeks of the Screening Visit.
21. Have used belatacept \<6 months prior to Clinic Visit 1
22. Have had an initial treatment of bronchial stents or cryotherapy within 12 months of the Screening Visit, or had bronchial stents removed within the last 3 months of the Screening Visit.

Where this trial is running

Phoenix, Arizona and 19 other locations

• Dignity Health - St. Joseph's Hospital and Medical Center — Phoenix, Arizona, United States (Withdrawn)
• University of California Los Angeles School of Medicine — Los Angeles, California, United States (Recruiting)
• University of California San Diego Health — San Diego, California, United States (Recruiting)
• Advent Health — Orlando, Florida, United States (Recruiting)
• University of South Florida — Tampa, Florida, United States (Recruiting)
• Loyola University Medical Center — Maywood, Illinois, United States (Recruiting)
• University of Iowa Hospital — Iowa City, Iowa, United States (Recruiting)
• Johns Hopkins Hospital — Baltimore, Maryland, United States (Recruiting)
• University of Minnesota Medical School — Minneapolis, Minnesota, United States (Withdrawn)
• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
• Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
• The Ohio State University Wexner Medical Center — Columbus, Ohio, United States (Recruiting)
• Temple University Hospital — Philadelphia, Pennsylvania, United States (Not_yet_recruiting)
• Medical University of South Carolina — Charleston, South Carolina, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• Baylor Scott and White Research Institute — Dallas, Texas, United States (Recruiting)
• Baylor St. Luke's Medical Center — Houston, Texas, United States (Recruiting)
• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
• Inova Fairfax Hospital — Falls Church, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Tim Whelan, MD — Medical University of South Carolina
• Study coordinator: Carolyn Durham, PhD

Conditions Pre-Bronchiolitis Obliterans Syndrome