Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough

Study Overview
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Brief Summary
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This is a randomized, Phase 2a, double-blind, placebo-controlled study to evaluate the safety and efficacy of ARINA-1 compared to placebo (isotonic saline, 0.9%) in participants with NCFBE. Study participants will receive either study treatment or placebo twice daily for 28 days. Efficacy endpoints will include quality of life, sputum rheological markers, and blood inflammatory markers. Quality of life will be measured using the following tools: Quality of Life-Bronchiectasis (QOL-B) questionnaire, St. George's Respiratory Questionnaire (SGRQ), Chronic Airways Assessment Test (CAAT), and a daily clinical global impression questionnaire.

Official Title
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A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of ARINA-1 in Adult Participants With Non-CF Bronchiectasis (NCFBE) With Excess Mucus and Cough

Conditions
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Non-cystic Fibrosis Bronchiectasis

Intervention / Treatment
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* Drug: ARINA-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of NCFBE confirmed by chest CT 18-80 years old, inclusive at time of informed consent BMI >18 Percent predicted FEV1 > 40%, pre-bronchodilator Stable for 90 days with any airway clearance technique (ACT) method(s) Stable on standard of care (SOC) therapy for 90 days (includes cycling antibiotics, such as inhaled tobramycin, and long-term macrolide therapy) and not likely, in the opinion of the investigator, to require any changes to therapy during the duration of study participation Fully vaccinated for COVID-19 (second dose of a 2-shot regimen or single dose of 1-shot regimen completed >14 days prior to the screening visit) Must be able to produce a sputum sample If female and of childbearing potential, must be willing to use contraception for the duration of the study. Exclusion Criteria Positive urine pregnancy test for women of childbearing potential (WOCBP) at screening and baseline visit Active exacerbation ≤28 days prior to the baseline visit Initiating or changing antibiotic, antiviral, or antifungal therapy ≤ 28 days prior to the baseline visit Changing or initiating any vitamin C, glutathione or N-acetyl-cysteine-containing therapy or multivitamin within 30 says prior to the screening visit. Positive COVID-19 diagnostic test (PCR or antigen) within 90 days prior to the screening visit. Participated in other interventional drug or device studies within 30 days of the screening visit (Note: observational studies are acceptable) Significant unstable comorbidities (in the opinion of the site investigator), such as heart failure, cardiovascular disease, diabetes, renal disease, liver disease Current tobacco or marijuana smoker (those with active smoking exposure <180 days prior to the screening visit) (Note: edibles are acceptable) Requiring the use of any supplemental oxygen Currently on cycled antibiotics (e.g., tobramycin) or have been on a cycled antibiotic regimen within 90 days prior to the screening visit. Current diagnosis of non-tuberculous mycobacteria (NTM) requiring antibiotic treatment. (Participants who test positive for NTM but who are not currently on antibiotic therapy are eligible for screening)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARINA-1<br>ARINA-1 (88 mg/mL ascorbic acid, ASC; 150 mg/mL reduced glutathione, GSH); fixed dose, 4 mL solution inhaled twice daily via nebulization for 28 days | Drug: ARINA-1<br>* ARINA-1 (88 mg/mL ascorbic acid, ASC; 150 mg/mL reduced glutathione, GSH)<br>|
| Placebo Comparator: Placebo<br>Isotonic saline (0.9%); 4 mL solution inhaled twice daily via nebulization for 28 days | Drug: Placebo<br>* Isotonic saline (0.9%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Incidence of participants that experience an adverse event following administration of treatment | 56 days | 
| Proportion of participants that experience each treatment-emergent adverse event |  | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare quality of life (as measured by CAAT questionnaire) between the ARINA-1 and placebo arms | 8 questions rated on a 0-5 scale | 56 days | 
| Compare quality of life (as measured by SGRQ) between the ARINA-1 and placebo arms | 42 questions, ranked on a 5-point descriptive scale or true/false | 56 days | 
| Compare quality of life (as measured by QOL-B) between the ARINA-1 and placebo arms | 37 questions ranked on a 4-point descriptive scale | 56 days | 
| Compare blood inflammatory markers between the ARINA-1 and placebo arms | C-reactive protein | 56 days | 
| Compare changes in mucolytic use between ARINA-1 and placebo arms | Compare the initiation or changes to regimen for drugs such as n-acetylcysteine, dornase alfa, etc. This information will be collected at all clinic visits and phone calls. | 56 days | 
| Compare changes in airway clearance techniques between ARINA-1 and placebo arms | Compare the initiation or changes to regimen for airway clearance techniques such as chest physical therapy, high-frequency oscillating vest therapy, etc. This information will be collected at all clinic visits and phone calls. | 56 days | 
| Compare FEV1 between the ARINA-1 and treatment arms | measured in L | 56 days | 
| Compare FVC between the ARINA-1 and treatment arms | measured in L | 56 days | 
| Compare FEF25-75 between the ARINA-1 and treatment arms | measured in L/sec | 56 days | 
| Compare PEF between the ARINA-1 and treatment arms | measured in L/min | 56 days | 
| Compare sputum percent solids between the ARINA-1 and placebo arms |  | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchiectasis