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

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

• Percentage change from baseline in FEV1 (%ΔFEV1) [Time frame: 24 weeks]

Secondary outcome measures (11)

• Percentage change from baseline of Forced Expiratory Volume in one second (FEV1) [Time frame: 48 weeks]
• Percentage change from baseline of Forced Vital Capacity (FVC) [Time frame: 24 weeks]
• Percentage change from baseline of FVC [Time frame: 48 weeks]
• Percentage change from baseline of FEF25-75% [Time frame: 24 weeks]
• Percentage change from baseline of FEF25-75% [Time frame: 48 weeks]
• Number of participants in each arm with augmented immunosuppression [Time frame: 24 weeks]
• Number of participants in each arm with augmented immunosuppression [Time frame: 48 weeks]
• Time to initiation of augmented immunosuppression [Time frame: over the duration of the 48 week trial]
• Change from baseline in Saint George's Respiratory Questionnaire total score [Time frame: 24 weeks]
• Change from baseline in Saint George's Respiratory Questionnaire total score [Time frame: 48 weeks]
• Proportion of participants requiring the use of antimicrobial agents to treat a pulmonary infection [Time frame: 48 weeks]

Eligibility criteria

Inclusion criteria

• 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
• 10-24% 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.

Exclusion criteria

• 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
• Significant unstable comorbidities, in the opinion of the site investigator
• Allery or previous adverse reaction to azithromycin
• A diagnosis of dynamic collapse / tracheobrochomalacia <90 days of the baseline visit.
• Subjects currently participating in, or who have participated in an interventional (drug or device) clinical study <30 days of the baseline visit.
• Have been diagnosed with ARAD within 6 weeks of the Screening Visit.
• Have used belatacept <6 months prior to Clinic Visit 1
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 22 centers

• Dignity Health - St. Joseph's Hospital and Medical Center — Phoenix
• University of California Los Angeles School of Medicine — Los Angeles
• University of California San Diego Health — San Diego
• Advent Health — Orlando
• University of South Florida — Tampa
• Loyola University Medical Center — Maywood
• University of Iowa Hospital — Iowa City
• Johns Hopkins Hospital — Baltimore
• … and 14 more centers

Identifiers

NCT: NCT05654922 · RVN-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗