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

Sponsor

Renovion, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05654922

Collaborator

(none)

100

Enrollment

Locations

Arms

Anticipated Duration (Months)

9.1

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to compare ARINA-1 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.

Condition or Disease	Intervention/Treatment	Phase
Pre-Bronchiolitis Obliterans Syndrome	Drug: ARINA-1 Other: Standard of care only	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

For individuals performing spirometry, every attempt will be made to keep them masked to treatment.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percentage change from baseline in FEV1 (%ΔFEV1) [24 weeks]
Week 24 (mL) - Baseline (mL) = ΔFEV1 (mL) ΔFEV1 (mL) / Baseline (mL) x 100 = %ΔFEV1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
10-20% 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 Screening
On a stable 3-agent immunosuppression regimen that includes a steroid, a calcineurin inhibitor (CNI), and cell cycle inhibitor (e.g., mycophenolate) >4 weeks prior to Screening

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
Advanced BOS (BOS 1-4) defined by >20% 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.
Currently using an mTOR inhibitor or azathioprine
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 baseline 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 or endobronchial stent <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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles (UCLA)	Los Angeles	California	United States	90095
2	University of California at San Diego	San Diego	California	United States	92103
3	University of South Florida - Tampa General Hospital	Tampa	Florida	United States	33606
4	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
5	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
6	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
7	Columbia University	New York	New York	United States	10032
8	Cleveland Clinic	Cleveland	Ohio	United States	44195
9	Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43221
10	Medical University of South Carolina	Charleston	South Carolina	United States	29425
11	Houston Methodist Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

Renovion, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Renovion, Inc.

ClinicalTrials.gov Identifier:

NCT05654922

Other Study ID Numbers:

RVN-001

First Posted:

Dec 16, 2022

Last Update Posted:

Jan 31, 2023

Last Verified:

Jan 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Bronchiolitis

Bronchiolitis Obliterans

Syndrome

Study Results

No Results Posted as of Jan 31, 2023