Clinical trial NCT03114020: Efficacy/Safety of HA Inhalation Solution for Hereditary Emphysema in Patients With Alpha-1 Antitrypsin Deficiency
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Emphysema
Alpha 1-Antitrypsin Deficiency
Keywords: Emphysema
COPD
Alpha-1 Antitrypsin Deficiency
Lead sponsor: Turino, Gerard, M.D.
Sponsor class: INDIV
First posted: 2017-04-14
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Measurement of sputum, plasma and urine concentrations of desmosine and isodesmosine
timeFrame: 28 days
measure: Assessment of pulmonary function tests
timeFrame: 28 days
Secondary outcomes:
measure: Assessment of St. George Respiratory Questionnaire
timeFrame: 28 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Fayetteville
country: United States
facility: Pulmonary Health Physicians, PC
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Tyler
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin / Froedtert Hospital
state: Wisconsin
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
Study officials:
affiliation: Mount Sinai St Lukes
name: Gerard M Turino, MD
role: PRINCIPAL_INVESTIGATOR
References: