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

Phase 2

Completed

• Conditions: Emphysema; Alpha 1-Antitrypsin Deficiency
• Interventions: Drug: Hyaluronic Acid Inhalation Solution; Drug: Placebo Inhalation Solution

• Registration Number: NCT03114020
• Lead Sponsor: Gerard Turino

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-03-22
• Study First Submitted: 2017-04-05
• Study First Submitted QC: 2017-04-10
• Study First Posted: 2017-04-14
• Primary Completion: 2019-11-12
• Study Completion: 2019-11-12
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-17
• Last Update Posted: 2020-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

1. Able and willing to provide written informed consent and comply with study requirements
2. Men or women aged 18 through 80 years at the time of consent
3. Diagnosis of emphysema at screening consistent with National Institutes of Health guidelines 19 GOLD COPD classification stages I, II or III
4. Evidence of emphysema on radiographic imaging.
5. A ratio of pre-bronchodilator FEV1 to forced vital capacity (FVC) of ≤ 80% at screening
6. FEV1 ≥ 30% and ≤ 79% (post-bronchodilator) of predicted normal at screening
7. Clinical laboratory tests (complete blood count, serum chemistry, and urinalysis) within normal limits or clinically acceptable to the PI and sponsor at screening
8. 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.
9. Evidence of alpha-1 antitrypsin deficiency (AATD) with any genotype except PiMZ deficiency. Individuals with PiMZ deficiency are not allowed in the study.
10. Patients must have stopped using Intravenous alpha-1 antitrypsin protein (AAT) augmentation therapy at least 3 months before entering study.

Exclusion Criteria

1. Subjects with measured DLCO of ≤ 35%, or unable to perform a reproducible DLCO
2. Subjects unable to perform 3 reproducible spirometry tests after 8 attempts
3. Upper or lower respiratory tract infection within 2 weeks prior to screening and baseline (day1)
4. Presence of clinically relevant abnormality on chest x-ray (other than evidence of emphysema) within the previous 12 months
5. Use of supplemental oxygen therapy
6. Requirement for ventilator support within the last year
7. Exacerbation requiring treatment with systemic corticosteroids within the last 3 months
8. History of lung transplant or liver transplant.
9. Presence of clinically relevant abnormality on electrocardiogram (ECG)
10. Any medical condition that, in the investigator's judgment, would compromise study participation or the evaluation of the study drug
11. Women who are pregnant or breastfeeding
12. Receipt of an investigational drug within 30 days prior to screening
13. Patients who are current smokers or have smoked within the last 3 months -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hyaluronic Acid inhalation solution	Hyaluronic Acid Inhalation Solution	3mL of 0.03% Hyaluronic Acid inhalation solution BID for 28 days
Placebo Inhalation Solution	Placebo Inhalation Solution	3mL matching placebo inhalation solution BID for 28 days

Primary Outcome Measures

Name	Time	Method
Assessment of pulmonary function tests	28 days	measurement of pulmonary function
Measurement of sputum, plasma and urine concentrations of desmosine and isodesmosine	28 days	measurement of biomarkers

Secondary Outcome Measures

Name	Time	Method
Assessment of St. George Respiratory Questionnaire	28 days	measurement of patient abilities

Trial Locations

Locations (6)

University of Texas Health Science Center; 🇺🇸 Tyler, Texas, United States

University of Miami Hospital; 🇺🇸 Miami, Florida, United States

Pulmonary Health Physicians, PC; 🇺🇸 Fayetteville, New York, United States

Inspiration Research Limited; 🇨🇦 Toronto, Ontario, Canada

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Medical College of Wisconsin / Froedtert Hospital; 🇺🇸 Milwaukee, Wisconsin, United States