Study Comparing Weekly Intravenous Administration of OctaAlpha1 With a Marketed Preparation Glassia® in Subjects With Alpha-1-antitrypsin Deficiency
- Registration Number
- NCT03385395
- Lead Sponsor
- Octapharma
- Brief Summary
This randomized trial is being conducted to show non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state. This will be conducted in individuals with alpha-1-antitrypsin deficiency and clinical evidence of emphysema.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
-
Any subject who needs chronic IV augmentation and maintenance therapy with A1PI because of congenital alpha-1-proteinase inhibitor (A1PI) deficiency and clinically diagnosed emphysema
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≥18 years of age
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Individuals with A1PI serum concentration <11 µM at screening
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Following bronchodilators:
- Initial FEV1(pred) between 25% and 75% or
- If the initial FEV1 was greater than 75% of predicted, a diffusing capacity of the lung for carbon monoxide (DLC O) less than 70% of predicted
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Following bronchodilators: Initial forced expiratory volume/forced vital capacity (FEV1/FVC) ratio less than 70%
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Non-smoking for at least 6 months before study treatment starts
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Able to understand and provide written informed consent
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Women of reproductive age: negative result of pregnancy test (human chorionic gonadotropin [HCG]-based assay) and agreement to use adequate contraception for the duration of the trial
- Any inflammatory condition or malignant tumor in the 7 days before treatment starts that according to investigator judgment might influence the metabolism of an enzyme inhibitor such as A1PI
- More than one A1PI-deficiency related exacerbation and/or hospitalization during the 3 months before study treatment starts
- Clinically significant liver or kidney disease in the preceding 6 months before study treatment starts
- Severe gas exchange abnormality (i.e., PaCO2 ≥46 mmHg)
- Known IgA deficiency with documented antibodies against IgA
- History of hypersensitivity to blood or plasma derived products, or any component of the product
- Known presence of antibodies against A1PI
- Seropositivity for HBsAg or HCV, HIV-1/2 IgG antibodies
- Administration of A1PI products in the 4 weeks before study treatment starts
- Participating in another clinical study currently or during the 3 months before study treatment starts.
- Live viral vaccination within the last month before study treatment starts
- A current life-threatening malignancy
- Emergency operation within 3 months before study treatment starts
- History of, or suspected, alcohol or drug abuse within 1 year before study treatment starts or currently on drug abuse therapy
- Pregnant and nursing women
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Glassia® Glassia - OctaAlpha1 OctaAlpha1 -
- Primary Outcome Measures
Name Time Method Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state 26 weeks Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state
- Secondary Outcome Measures
Name Time Method Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (t1/2) Time period including days 1 to 14 after first infusion in study Compare PK parameters following a single dose between the two treatment groups calculating t1/2 (apparent terminal half-life)
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (Cmax) Time period including days 1 to 14 after first infusion in study Compare PK parameters following a single dose between the two treatment groups calculating maximum plasma concentration (Cmax)-ratio: 90% CI should lie within 80%-125%
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (tmax) Time period including days 1 to 14 after first infusion in study Compare PK parameters following a single dose between the two treatment groups calculating tmax (time to reach maximum serum concentration)
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hemoglobin 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hemoglobin via lab test
Investigate the pharmacodynamics of OctaAlpha1 measuring Induced sputum test measuring the amount of functional and total A1PI in the airway lining fluid of the lung. 26 weeks Investigate the pharmacodynamics of OctaAlpha1 measuring Induced sputum test measuring the amount of functional and total A1PI in the airway lining fluid of the lung.
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (λZ) Time period including days 1 to 14 after first infusion in study Compare PK parameters following a single dose between the two treatment groups calculating λZ (apparent terminal elimination rate constant determined by log-linear regression analysis)
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on respiratory rate 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on respiratory rate
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (AUC) Time period including days 1 to 14 after first infusion in study Compare PK parameters following a single dose between the two treatment groups calculating area under the plasma concentration-time curve (AUC)-ratio: 90% confidence interval (CI) should lie within 80%-125%.
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter aspartate aminotransferase 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter aspartate aminotransferase via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter creatinine 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter creatinine via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hematocrit 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hematocrit via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter white blood cells 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter white blood cells via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter platelet count 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter platelet count via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter Blood Urea Nitrogen (BUN) 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter Blood Urea Nitrogen (BUN) via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on occurrence of adverse events 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on occurrence of adverse events
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on blood pressure 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on blood pressure
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on body temperature 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on body temperature
Pharmacodynamics of OctaAlpha1 measuring Pulmonary function tests 26 weeks Investigate the pharmacodynamics of OctaAlpha1 measuring Pulmonary function tests (done according to the American Thoracic Society/European Respiratory Society Taskforce Standardisation of Lung Function Testing guideline)
Investigate the pharmacodynamics of OctaAlpha1 measuring Induced sputum test measuring the amount of functional and total LTB4 in the airway lining fluid of the lung. 26 weeks Investigate the pharmacodynamics of OctaAlpha1 measuring Induced sputum test measuring the amount of functional and total LTB4 in the airway lining fluid of the lung.
Investigate the pharmacodynamics of OctaAlpha1 measuring antibodies to A1PI using normal ranges of the central laboratory 26 weeks Investigate the pharmacodynamics of OctaAlpha1 measuring antibodies to A1PI using normal ranges of the central laboratory
Determine PK parameters of the A1PI serum concentration versus time curve following a single dose of OctaAlpha1 26 weeks Determine PK parameters of the A1PI serum concentration versus time curve following a single dose of OctaAlpha1
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter alanine aminotransferase 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter alanine aminotransferase via lab test
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on viral safety (HAV, HBV, HCV, HIV-1/2, HN, and parvovirus B19) 26 weeks Evaluate descriptively the safety and tolerability of OctaAlpha1 based on viral safety (HAV, HBV, HCV, HIV-1/2, HN, and parvovirus B19)
Trough Levels of A1PI 26 weeks Investigate descriptively the trough levels of A1PI and anti-NE capacity of OctaAlpha1 compared to Glassia®