Alpha 1-Antitrypsin Deficiency
Conditions
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.
Interventions
DRUGOctaAlpha1
For OctaAlpha1 the standard weekly dose of 60mg/kg will be given for 24 consecutive infusions
DRUGGlassia
For Glassia the standard weekly dose of 60mg/kg will be given for 24 consecutive infusions
Sponsors
Octapharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * ≥18 years of age * Individuals with A1PI serum concentration \<11 µM at screening * 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 * Following bronchodilators: Initial forced expiratory volume/forced vital capacity (FEV1/FVC) ratio less than 70% * Non-smoking for at least 6 months before study treatment starts * Able to understand and provide written informed consent * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 (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 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 |
| 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 |
| 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 hemoglobin | 26 weeks | Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hemoglobin 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 |
| 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 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 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 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 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® |
| 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 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. |
| 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 hematological parameter platelet count | 26 weeks | Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter platelet count via lab test |
Outcome results
None listed