Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant

NCT05654922 | Recruiting Phase 3 FDA Drug

• 1 other identifier: RVN-001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 20

Brief Summary

The goal of this Phase 3 clinical trial is to compare ARINA-1 (a nebulized immunomodulatory agent) plus Standard of Care vs Standard of Care alone. The main question it aims to answer are:

• Evaluate the effectiveness of ARINA-1 in preventing bronchiolitis obliterans syndrome (BOS) progression in participants with a bilateral lung transplant
• To evaluate the effectiveness of ARINA-1 on improving quality of life decline and preventing or delaying the use of augmented immunosuppression in participants with pre-BOS relative to SOC. Participants will have clinic visits at screening, randomization (day 1) and weeks 4, 12, 18, and 24. After week 24, participants will have clinic visits at weeks 32, 40, and 48. Participants will also have a telehealth visit on day 2 and phone calls to assess adverse events (AEs), serious adverse events (SAEs), and review patient education will occur during weeks 5, 8, 36, and 44.

Conditions

Pre-Bronchiolitis Obliterans Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage change from baseline in FEV1 (%ΔFEV1)

  Week 24 (mL) - Baseline (mL) = ΔFEV1 (mL) ΔFEV1 (mL) / Baseline (mL) x 100 = %ΔFEV1

  24 weeks

Secondary Outcomes (11)

• Percentage change from baseline of Forced Expiratory Volume in one second (FEV1)

  48 weeks

• Percentage change from baseline of Forced Vital Capacity (FVC)

  24 weeks

• Percentage change from baseline of FVC

  48 weeks

• Percentage change from baseline of FEF25-75%

  24 weeks

• Percentage change from baseline of FEF25-75%

  48 weeks

Study Arms (2)

ARINA-1 plus standard of care

EXPERIMENTAL

ARINA-1 (88 mg/mL ascorbic acid, ASC; 150 mg/mL reduced glutathione, GSH); fixed dose, 4 mL solution inhaled twice daily via nebulization plus standard 3-therapy immunosuppression regimen and azithromycin

Drug: ARINA-1

Standard of care only

OTHER

Standard 3-therapy immunosuppression regimen and azithromycin

Other: Standard of care only

Interventions

ARINA-1 DRUG

ARINA-1 (88 mg/mL ascorbic acid, ASC; 150 mg/mL reduced glutathione, GSH)

ARINA-1 plus standard of care

Standard of care only OTHER

Standard 3-therapy immunosuppression regimen and azithromycin

Standard of care only

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Bilateral lung transplant \>12 months from the time of Visit 1 / Randomization
• Age 18-75 years old at the time of consent
• Routinely followed at enrolling site
• Willing and able to comply with visit schedule and at-home requirements
• % decrease in FEV1 from the post-transplant baseline within the last 12 months.
• Capable of giving informed consent
• On a stable maintenance regimen of azithromycin for \>4 weeks prior to the Screening Visit
• 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
• If a woman of childbearing potential (WOCBP), must agree to use a reliable method of birth control for the entire duration of the study.

You may not qualify if:

• Positive urine pregnancy test at screening and baseline visit
• Diagnosis of active congestive heart failure or symptomatic coronary artery disease \> grade 3 based on the New York Heart Association Functional Classification (NYHA) criteria
• Restrictive allograft syndrome (RAS) defined by radiographic interstitial or alveolar opacities on chest X-ray or CT scan that are consistent with RAS
• Have advanced BOS, defined by \>24% decrease in FEV1 in post-transplant baseline
• A diagnosis of probable antibody-mediated rejection (AMR) \<12 months prior to the baseline visit
• 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.
• Unresolved diffuse alveolar damage
• Receiving mechanical ventilation
• Chronic kidney disease stage IV or higher, including on dialysis
• Initiating a new maintenance therapy or changing immunosuppression maintenance therapy (e.g., changing tacrolimus to cyclosporine) \<30 days prior to the baseline visit.
• Have initiated or changed mTOR maintenance therapy \<3 months prior to Clinic Visit 1 (mTOR use for \>3 months is allowed)
• Initiating or changing antibiotic (including azithromycin), antiviral, or antifungal therapy \<14 days prior to the baseline visit.
• Use of alemtuzumab \<6 months prior to the baseline visit
• 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.
• Initiating a multivitamin or other supplement (inhaled, oral, or IV) containing vitamin C, glutathione, or N-acetylcysteine \<90 days prior to the baseline visit

Sponsors & Collaborators

• Renovion, Inc.: lead

Study Sites (20)

Dignity Health - St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

WITHDRAWN

University of California Los Angeles School of Medicine

Los Angeles, California, 90095, United States

RECRUITING

University of California San Diego Health

San Diego, California, 92103, United States

RECRUITING

Advent Health

Orlando, Florida, 32803, United States

RECRUITING

University of South Florida

Tampa, Florida, 33606, United States

RECRUITING

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

University of Iowa Hospital

Iowa City, Iowa, 52242, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

WITHDRAWN

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43221, United States

RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, 19122, United States

NOT YET RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29452, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 45390, United States

RECRUITING

Baylor Scott and White Research Institute

Dallas, Texas, 75246, United States

RECRUITING

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

RECRUITING

Study Officials

• Tim Whelan, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carolyn Durham, PhD

CONTACT

919-240-7034; info@renovion.com

Will Anderson

CONTACT

919-240-7034; info@renovion.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: For individuals performing spirometry, every attempt will be made to keep them masked to treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 16, 2022
• Study Start: April 10, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

US (20)