Pulmonary Emphysema in Alpha-1 PI Deficiency Clinical Trial
— SPARTAOfficial title:
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
| Verified date | March 2024 |
| Source | Grifols Therapeutics LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 345 |
| Est. completion date | January 2027 |
| Est. primary completion date | August 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 70 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Royal Adelaide Hospital | Adelaide | South Australia |
| Australia | The Prince Charles Hospital | Chermside | Queensland |
| Australia | St Vincent's Hospital Melbourne | Fitzroy | Victoria |
| Australia | Institute for Respiratory Health Inc | Nedlands | Western Australia |
| Australia | St Vincent's Hospital Sydney | Sydney | New South Wales |
| Brazil | Faculdade de Medicina do ABC | Santo André | Sao Paulo |
| Brazil | Instituto do Coração - Incor- HCFMUSP | São Paulo | |
| Brazil | UNIFESP - Universidade Federal de São Paulo | São Paulo | Sao Paulo |
| Canada | Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia |
| Canada | Health Sciences Centre | St. John's | Newfoundland and Labrador |
| Canada | Inspiration Research Limited | Toronto | Ontario |
| Denmark | Århus Universitetshospital | Arhus C | |
| Denmark | Gentofte Hospital | Hellerup | |
| Estonia | North Estonia Medical Centre Foundation | Tallinn | |
| Estonia | Tartu University Hospital | Tartu | |
| Finland | Turku University Central Hospital, Department of Pulmonary Diseases | Turku | |
| France | Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel | Bron | Rhone |
| New Zealand | New Zealand Respiratory and Sleep institute | Auckland | |
| New Zealand | Christchurch Hospital NZ | Christchurch | |
| New Zealand | Waikato Hospital | Hamilton | |
| Poland | SPZOZ Szpital Uniwersytecki w Krakowie | Krakow | |
| Poland | Instytut Gruzlicy i Chorob Pluc w Warszawie | Warszawa | |
| Russian Federation | SBEI HPE Altai State Medical University of MoH and SD | Barnaul | |
| Russian Federation | SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev | Yaroslavl | |
| Sweden | Sahlgrenska Sjukhuset | Göteborg | |
| Sweden | CTC - Clinical Trial Consultants AB | Linköping | |
| Sweden | Skånes Universitetssjukhus, Malmö | Malmö | |
| Sweden | Karolinska Universitetssjukhuset, Solna | Stockholm | |
| Sweden | CTC Clinical Trial Consultants AB | Uppsala | |
| United States | Medical University of South Carolina | Charleston | South Carolina |
| United States | University of Miami Miller School of Medicine | Miami | Florida |
| United States | St. Joseph's Hospital and Medical Center | Phoenix | Arizona |
| United States | Oregon Health & Science University | Portland | Oregon |
| United States | University of Texas Health Center at Tyler | Tyler | Texas |
| United States | Accellacare | Wilmington | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Grifols Therapeutics LLC |
United States, Australia, Brazil, Canada, Denmark, Estonia, Finland, France, New Zealand, Poland, Russian Federation, Sweden,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change from Baseline in Whole lung PD15 (15th percentile point) | Whole lung PD15 measured by CT scan | Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156 | |
| Secondary | Adverse Events (AEs) | Monitoring of AEs | Week -3 through Week 160 | |
| Secondary | Serious Adverse Events (SAEs) | Monitoring of SAEs | Week -3 through Week 160 | |
| Secondary | Discontinuations from the study due to AEs | Monitoring of discontinuations due to AEs | Week -3 through Week 160 | |
| Secondary | Severe COPD Exacerbations | Severe COPD exacerbations as defined by American Thoracic Society/European Respiratory Society (ATS/ERS) criteria (i.e., COPD exacerbations requiring hospitalization) | Week -3 through Week 160 | |
| Secondary | Change from Baseline in PD15 of the basal lung region | PD15 of the basal lung region measure by CT scan | Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156 | |
| Secondary | Change from baseline in carbon monoxide diffusing capacity (DLco) | DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines | Weeks 26, 52, 78, 104, 130 and 156 | |
| Secondary | Changes from baseline in forced expiratory volume in 1 second (FEV1) | FEV1 performed according to ATS/ERS guidelines | Weeks 26, 52, 78, 104, 130 and 156 | |
| Secondary | Change from baseline in Saint George's Respiratory Questionnaire: Minimum value = 0, maximum value = 100, higher scores indicate worse condition | Health-related quality of life assessment tool | Weeks 26, 52, 78, 104, 130 and 156 | |
| Secondary | 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 | Heath-related quality of life assessment tool | Weeks 26, 52, 78, 104, 130 and 156 |