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

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

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

Study Overview

• Status: Completed
• Conditions: Emphysema; Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: Hyaluronic Acid Inhalation Solution; Drug: Placebo Inhalation Solution

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 3A9
      • Inspiration Research Limited
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
  • New York
    • Fayetteville, New York, United States, 13066
      • Pulmonary Health Physicians, PC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Tyler, Texas, United States, 75708
      • University of Texas Health Science Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin / Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gerard Turino
• Investigators: Principal Investigator: Gerard M Turino, MD, Mount Sinai St Lukes

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2017
• Primary Completion (Actual): November 12, 2019
• Study Completion (Actual): November 12, 2019

Study Registration Dates

• First Submitted: April 5, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 17, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: COPD; Alpha-1 Antitrypsin Deficiency; Emphysema
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Subcutaneous Emphysema; Pulmonary Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Pharmaceutical Solutions; Hyaluronic Acid
• Other Study ID Numbers: C100-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No