Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD)

Phase 3

Active, not recruiting

• Conditions: Pulmonary Emphysema in Alpha-1 PI Deficiency
• Interventions: Other: 0.9% Sodium Chloride for Injection, USP; Biological: Alpha-1 MP

• Registration Number: NCT01983241
• Lead Sponsor: Grifols Therapeutics LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-10-28
• Study Start: 2013-11
• Study First Submitted QC: 2013-11-07
• Study First Posted: 2013-11-13
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-14
• Last Update Posted: 2025-01-15
• Primary Completion: 2026-08
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 345

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.
• Use of systemic or aerosolized antibiotics for a COPD exacerbation within the 5 weeks prior to the Screening Visit or during the Screening Phase.
• Known selective or severe Immunoglobulin A (IgA) deficiency.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	0.9% Sodium Chloride for Injection, USP	0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks
Alpha-1 MP 120 mg/kg	Alpha-1 MP	Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks
Alpha-1 MP 60 mg/kg	Alpha-1 MP	Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Whole lung PD15 (15th percentile point)	Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156	Whole lung PD15 measured by CT scan

Secondary Outcome Measures

Name	Time	Method
Discontinuations from the study due to AEs	Week -3 through Week 160	Monitoring of discontinuations due to AEs
Changes from baseline in forced expiratory volume in 1 second (FEV1)	Weeks 26, 52, 78, 104, 130 and 156	FEV1 performed according to ATS/ERS guidelines
Severe COPD Exacerbations	Week -3 through Week 160	Severe COPD exacerbations as defined by American Thoracic Society/European Respiratory Society (ATS/ERS) criteria (i.e., COPD exacerbations requiring hospitalization)
Change from Baseline in PD15 of the basal lung region	Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156	PD15 of the basal lung region measure by CT scan
Change from baseline in carbon monoxide diffusing capacity (DLco)	Weeks 26, 52, 78, 104, 130 and 156	DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
Adverse Events (AEs)	Week -3 through Week 160	Monitoring of AEs
Serious Adverse Events (SAEs)	Week -3 through Week 160	Monitoring of SAEs
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	Health-related quality of life assessment tool
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	Heath-related quality of life assessment tool

Trial Locations

Locations (52)

Institutul de Ftiziopneumologie "Chiril Draganiuc"; 🇲🇩 Chisinau, Moldova, Republic of

St. Joseph's Hospital and Medical Center; 🇺🇸 Phoenix, Arizona, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Medical Research of Central Florida, LLC; 🇺🇸 Leesburg, Florida, United States

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Accellacare; 🇺🇸 Wilmington, North Carolina, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Penn State Univ. Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

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

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