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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pre-Bronchiolitis Obliterans Syndrome
• Intervention / Treatment: Drug: ARINA-1; Other: Standard of care only

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Carolyn Durham, PhD; Phone Number: 919-240-7034; Email: info@renovion.com
• Study Contact Backup: Name: Will Anderson; Phone Number: 919-240-7034; Email: info@renovion.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Withdrawn
      • Dignity Health - St. Joseph's Hospital and Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles School of Medicine
      • Contact: Paul Lopez; Phone Number: 310-794-8595; Email: plopez@mednet.ucla.edu
      • Principal Investigator: Sam Weigt, MD
    • San Diego, California, United States, 92103
      • Recruiting
      • University of California San Diego Health
      • Contact: Amber Martineau; Phone Number: 619-471-0817; Email: ajm002@health.ucsd.edu
      • Principal Investigator: Kamyar Afshar, MD
  • Florida
    • Orlando, Florida, United States, 32803
      • Recruiting
      • Advent Health
      • Contact: Zoe Bancilhon, MPH; Email: zoe.bancilhon@adventhealth.com
      • Contact: 4076094574
      • Principal Investigator: Suresh Manickavel, MD
    • Tampa, Florida, United States, 33606
      • Recruiting
      • University of South Florida
      • Contact: Michelle Beck; Email: mbeck@tgh.org
      • Principal Investigator: Muhammed Qureshi, MD
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Recruiting
      • Loyola University Medical Center
      • Principal Investigator: Daniel Dilling, MD
      • Contact: Josie Corral; Phone Number: 888-584-7888; Email: Jcorral@luc.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospital
      • Principal Investigator: Tahuanty Pena, MD
      • Contact: Mary Teresi; Phone Number: 319-384-7546; Email: mary-teresi@uiowa.edu
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Joby Mathew; Phone Number: 410-550-6458; Email: jmathe27@jhmi.edu
      • Principal Investigator: Christian Merlo, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Withdrawn
      • University of Minnesota Medical School
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Brigitte Mittler; Phone Number: 314-747-1931; Email: b.mittler@wustl.edu
      • Principal Investigator: Chad Witt, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Principal Investigator: Selim Arcasoy, MD
      • Contact: Leo Suarez; Phone Number: 646 528-9006; Email: ls955@cumc.columbia.edu
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Marie Budev, MD
      • Contact: Joanne Baran; Phone Number: 216-894-3826; Email: BARANJ2@ccf.org
    • Columbus, Ohio, United States, 43221
      • Recruiting
      • The Ohio State University Wexner Medical CEnter
      • Principal Investigator: Justin Rosenheck, MD
      • Contact: Sydney Martin; Phone Number: 614 366-2775; Email: Sydney.Martin@osumc.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19122
      • Not yet recruiting
      • Temple University Hospital
      • Principal Investigator: Rachel Criner, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29452
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Tim Whelan, MD
      • Contact: Sara Garcia, MS; Phone Number: 8437925885; Email: garcisar@musc.edu
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor Scott and White Research Institute
      • Contact: Felicia Padilla; Phone Number: 214-820-1771; Email: Felicia.Padilla@bswhealth.org
      • Contact: Kristen Paasch; Phone Number: 214-865-4994; Email: Kristen.Paasch@BSWHealth.org
      • Principal Investigator: Todd Grazia, MD
    • Dallas, Texas, United States, 45390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Rama Diallo; Email: Ramatoulaye.Diallo@utsouthwestern.edu
      • Principal Investigator: Vaidehi Kaza, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
      • Principal Investigator: Howard Huang, MD
      • Contact: Serene Shaham, RN; Phone Number: 346-238-4586; Email: sashaham@houstonmethodist.org
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor St. Luke's Medical Center
      • Contact: Maria Perea, MD; Phone Number: (832) 355-9494; Email: maria.perea@bcm.edu
      • Principal Investigator: Prangthip Charoenpong, MD, MPH
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Recruiting
      • Inova Fairfax Hospital
      • Contact: Paige Thibodeaux; Phone Number: 703.776.4353; Email: Paige.Thibodeaux@inova.org
      • Principal Investigator: Shambhu Aryal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARINA-1 plus standard of care; 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; ARINA-1 (88 mg/mL ascorbic acid, ASC; 150 mg/mL reduced glutathione, GSH)
Other: Standard of care only; Standard 3-therapy immunosuppression regimen and azithromycin	Other: Standard of care only; Standard 3-therapy immunosuppression regimen and azithromycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change from baseline in FEV1 (%ΔFEV1)	Week 24 (mL) - Baseline (mL) = ΔFEV1 (mL) ΔFEV1 (mL) / Baseline (mL) x 100 = %ΔFEV1	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change from baseline of Forced Expiratory Volume in one second (FEV1)	Week 48 (mL) - Baseline (mL) = ΔFEV1 (mL) ΔFEV1 (mL) / Baseline (mL) x 100 = %ΔFEV1	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
Number of participants in each arm with augmented immunosuppression	number	24 weeks
Number of participants in each arm with augmented immunosuppression		48 weeks
Time to initiation of augmented immunosuppression	Length of time to when participant requires a change in their immunosuppression regimen	over the duration of the 48 week trial
Change from baseline in Saint George's Respiratory Questionnaire total score	quality of life questionnaire, total score of 0 to 100, higher score = more limitations	24 weeks
Change from baseline in Saint George's Respiratory Questionnaire total score	quality of life questionnaire, total score of 0 to 100, higher score = more limitations	48 weeks
Proportion of participants requiring the use of antimicrobial agents to treat a pulmonary infection		48 weeks

Collaborators and Investigators

• Sponsor: Renovion, Inc.
• Investigators: Principal Investigator: Tim Whelan, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organizing Pneumonia; Pathologic Processes; Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Disease; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Syndrome; Bronchiolitis; Bronchiolitis Obliterans
• Other Study ID Numbers: RVN-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No