Clinical trial NCT05654922: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pre-Bronchiolitis Obliterans Syndrome
Lead sponsor: Renovion, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage change from baseline in FEV1 (%ΔFEV1)
timeFrame: 24 weeks
Secondary outcomes:
measure: Percentage change from baseline of Forced Expiratory Volume in one second (FEV1)
timeFrame: 48 weeks
measure: Percentage change from baseline of Forced Vital Capacity (FVC)
timeFrame: 24 weeks
measure: Percentage change from baseline of FVC
timeFrame: 48 weeks
measure: Percentage change from baseline of FEF25-75%
timeFrame: 24 weeks
measure: Percentage change from baseline of FEF25-75%
timeFrame: 48 weeks
measure: Number of participants in each arm with augmented immunosuppression
timeFrame: 24 weeks
measure: Number of participants in each arm with augmented immunosuppression
timeFrame: 48 weeks
measure: Time to initiation of augmented immunosuppression
timeFrame: over the duration of the 48 week trial
measure: Change from baseline in Saint George's Respiratory Questionnaire total score
timeFrame: 24 weeks
measure: Change from baseline in Saint George's Respiratory Questionnaire total score
timeFrame: 48 weeks
measure: Proportion of participants requiring the use of antimicrobial agents to treat a pulmonary infection
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Dignity Health - St. Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles School of Medicine
state: California
city: San Diego
country: United States
facility: University of California San Diego Health
state: California
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospital
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: Barnes-Jewish Hospital / Washington University
name: Ramsey Hachem, MD
role: PRINCIPAL_INVESTIGATOR
References: