A Randomized, Double-Blind, Placebo Controlled Study to Assess the Efficacy and Safety of Two Dose Regimens (60 mg/kg and 120 mg/kg) of Weekly Intravenous Alpha1 Proteinase Inhibitor (Human) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency

Grifols Therapeutics LLC52 sites in 17 countries345 target enrollmentNovember 1, 2013

ConditionsPulmonary Emphysema in Alpha-1 PI Deficiency

Interventions0.9% Sodium Chloride for Injection, USP Alpha-1 MP

DrugsAlpha-1 MP

Overview

Phase: Phase 3
Intervention: 0.9% Sodium Chloride for Injection, USP
Conditions: Pulmonary Emphysema in Alpha-1 PI Deficiency
Sponsor: Grifols Therapeutics LLC
Enrollment: 345
Locations: 52
Primary Endpoint: Change from Baseline in Whole lung PD15 (15th percentile point)
Status: Active, Not Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multi-center, randomized, placebo-controlled, double blind clinical study to assess the efficacy and safety of two separate dose regimens of Alpha-1 MP versus placebo for 156 weeks (i.e., 3 years) using computed tomography (CT) of the lungs as the main measure of efficacy. The two Alpha-1 MP doses to be tested are 60 mg/kg and 120 mg/kg administered weekly by IV infusion for 156 weeks. The study consists of an optional pre-screening phase, Screening Phase, a 156-week Treatment Phase, and an End of Study Visit at Week 160.

Registry

clinicaltrials.gov

Start Date

November 1, 2013

End Date

January 1, 2027

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Grifols Therapeutics LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have a documented total alpha1-PI serum level \< 11 µM.
•Have a diagnosis of congenital AATD with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or "at-risk" alleles.
•At the Screening (Week -3) Visit, have a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 30% and \< 80% of predicted and FEV1/forced vital capacity (FVC) \< 70% (Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] stage II or III).
•Have a carbon monoxide diffusing capacity (DLCO) ≤ 60% of predicted (corrected for HgB) within the past 2 years OR evidence of pulmonary emphysema on CT scan within the past 2 years per the Investigator's judgment.
•Have clinical evidence of pulmonary emphysema per the Investigator's judgment.

Exclusion Criteria

•Has received alpha1-PI augmentation therapy for more than 1 month within the six months prior to the Screening Visit.
•Has received alpha1-PI augmentation therapy within one month of the Screening Visit.
•Has had a chronic obstructive pulmonary disease (COPD) exacerbation within the 5 weeks prior to the Screening Visit or during the Screening Phase.
•Unable to physically (e.g., unable to fit inside the CT scanner) or mentally (e.g., claustrophobic) undergo a CT scan.
•History of lung or liver transplant.
•Any lung surgery during the past 2 years (excluding lung biopsy).
•On the waiting list for lung surgery, including lung transplant.
•Smoking during the past 12 months or a positive urine cotinine test at screening that is due to smoking. Maybe on Nicotine replacement, including vapor cigarettes.
•History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s).
•Use of systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e., 10 mg every 2 days) within the 5 weeks prior to the Screening Visit (inhaled steroids are not considered systemic steroids) or during the Screening Phase.

Arms & Interventions

Placebo

0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks

Intervention: 0.9% Sodium Chloride for Injection, USP

Alpha-1 MP 60 mg/kg

Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks

Intervention: Alpha-1 MP

Alpha-1 MP 120 mg/kg

Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks

Intervention: Alpha-1 MP

Outcomes

Primary Outcomes

Change from Baseline in Whole lung PD15 (15th percentile point)

Time Frame: Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156

Whole lung PD15 measured by CT scan

Secondary Outcomes

Discontinuations from the study due to AEs(Week -3 through Week 160)
Changes from baseline in forced expiratory volume in 1 second (FEV1)(Weeks 26, 52, 78, 104, 130 and 156)
Severe COPD Exacerbations(Week -3 through Week 160)
Change from Baseline in PD15 of the basal lung region(Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156)
Change from baseline in carbon monoxide diffusing capacity (DLco)(Weeks 26, 52, 78, 104, 130 and 156)
Adverse Events (AEs)(Week -3 through Week 160)
Serious Adverse Events (SAEs)(Week -3 through Week 160)
Change from baseline in Saint George's Respiratory Questionnaire: Minimum value = 0, maximum value = 100, higher scores indicate worse condition(Weeks 26, 52, 78, 104, 130 and 156)
Change from baseline in the EuroQoL (Quality of Life)- 5 Dimension- 5 Level (EQ-5D-5L): Minimum value (for each one of the 5 levels) = 1, maximum value (for each one of the 5 levels) = 5, higher scores indicate worse condition(Weeks 26, 52, 78, 104, 130 and 156)