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

Gerard Turino

Status and phase: Completed; Phase 2

Conditions: Emphysema; Alpha 1-Antitrypsin Deficiency

Treatments: Drug: Hyaluronic Acid Inhalation Solution; Drug: Placebo Inhalation Solution

Study type: Interventional

Identifiers

NCT03114020

C100-008

Details and patient eligibility

About

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

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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 -

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

27 participants in 2 patient groups, including a placebo group

Hyaluronic Acid inhalation solution

Experimental group

Description:

3mL of 0.03% Hyaluronic Acid inhalation solution BID for 28 days

Treatment:

Drug: Hyaluronic Acid Inhalation Solution

Placebo Inhalation Solution

Placebo Comparator group

Description:

3mL matching placebo inhalation solution BID for 28 days

Treatment:

Drug: Placebo Inhalation Solution