Study Comparing Weekly Intravenous Administration of OctaAlpha1 With a Marketed Preparation Glassia® in Subjects With Alpha-1-antitrypsin Deficiency

Octapharma

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Alpha 1-Antitrypsin Deficiency

Interventions

OctaAlpha1DRUG

For OctaAlpha1 the standard weekly dose of 60mg/kg will be given for 24 consecutive infusions

GlassiaDRUG

For Glassia the standard weekly dose of 60mg/kg will be given for 24 consecutive infusions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state

Time frame: 26 weeks

Secondary Outcomes

Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (AUC)

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%.