Efficacy/Safety of HA Inhalation Solution for Hereditary Emphysema in Patients With Alpha-1 Antitrypsin Deficiency

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and efficacy of administering repeated doses of Hyaluronic Acid Inhalation Solution to subjects with Emphysema that have Alpha-1-Antitrypsin deficiency

Detailed Description
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The study primarily aims to establish desmosine and isodesmosine concentrations in plasma, sputum and urine measured as markers of elastin degradation systemically in the lung and also markers of inflammation and fibrinogen. Assessment of vital signs, lab tests, carbon monoxide diffusing capacity, oxygen saturation, pulmonary function tests, ECGs, physical exams and adverse events.

Official Title
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Phase 2 Randomized Parallel-Group Double-Blind Placebo-Controlled Multiple-Dose Proof-of-Concept Study to Evaluate the Efficacy/Safety of Hyaluronic Acid Inhalation Solution for Treatment of Emphysema

Conditions
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Emphysema, Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
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* Drug: Hyaluronic Acid Inhalation Solution
* Drug: Placebo Inhalation Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide written informed consent and comply with study requirements Men or women aged 18 through 80 years at the time of consent Diagnosis of emphysema at screening consistent with National Institutes of Health guidelines 19 GOLD COPD classification stages I, II or III Evidence of emphysema on radiographic imaging. A ratio of pre-bronchodilator FEV1 to forced vital capacity (FVC) of ≤ 80% at screening FEV1 ≥ 30% and ≤ 79% (post-bronchodilator) of predicted normal at screening Clinical laboratory tests (complete blood count, serum chemistry, and urinalysis) within normal limits or clinically acceptable to the PI and sponsor at screening Women of childbearing potential and men who are sexually active must agree to use an adequate method of contraception (oral contraceptives, depot progesterone, condom plus spermicidal, or IUD) during the study and for 1 month after the final dose of study drug. Evidence of alpha-1 antitrypsin deficiency (AATD) with any genotype except PiMZ deficiency. Individuals with PiMZ deficiency are not allowed in the study. Patients must have stopped using Intravenous alpha-1 antitrypsin protein (AAT) augmentation therapy at least 3 months before entering study. Exclusion Criteria: Subjects with measured DLCO of ≤ 35%, or unable to perform a reproducible DLCO Subjects unable to perform 3 reproducible spirometry tests after 8 attempts Upper or lower respiratory tract infection within 2 weeks prior to screening and baseline (day1) Presence of clinically relevant abnormality on chest x-ray (other than evidence of emphysema) within the previous 12 months Use of supplemental oxygen therapy Requirement for ventilator support within the last year Exacerbation requiring treatment with systemic corticosteroids within the last 3 months History of lung transplant or liver transplant. Presence of clinically relevant abnormality on electrocardiogram (ECG) Any medical condition that, in the investigator's judgment, would compromise study participation or the evaluation of the study drug Women who are pregnant or breastfeeding Receipt of an investigational drug within 30 days prior to screening Patients who are current smokers or have smoked within the last 3 months -

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyaluronic Acid inhalation solution<br>3mL of 0.03% Hyaluronic Acid inhalation solution BID for 28 days | Drug: Hyaluronic Acid Inhalation Solution<br>* twice a day 3 mL of 0.03% Hyaluronic Acid Inhalation Solution<br>* Other names: active inhalation solution;|
| Placebo Comparator: Placebo Inhalation Solution<br>3mL matching placebo inhalation solution BID for 28 days | Drug: Placebo Inhalation Solution<br>* Twice a day 3 ml of placebo inhalation solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of sputum, plasma and urine concentrations of desmosine and isodesmosine | measurement of biomarkers | 28 days | 
| Assessment of pulmonary function tests | measurement of pulmonary function | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of St. George Respiratory Questionnaire | measurement of patient abilities | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Emphysema, Alpha-1 Antitrypsin Deficiency