Clinical trial NCT03385395: Study Comparing Weekly Intravenous Administration of OctaAlpha1 With a Marketed Preparation Glassia® in Subjects With Alpha-1-antitrypsin Deficiency
Official title: A Randomized, Double-blind, Parallel-group, Multicenter, Pharmacokinetic Study Comparing Weekly Intravenous Administration of OctaAlpha1 (Octapharma) With a Marketed Preparation Glassia® (Kamada Ltd.) in Subjects With Alpha-1-antitrypsin Deficiency
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Alpha 1-Antitrypsin Deficiency
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2017-12-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state
timeFrame: 26 weeks
Secondary outcomes:
measure: Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (AUC)
timeFrame: Time period including days 1 to 14 after first infusion in study
measure: Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (Cmax)
timeFrame: Time period including days 1 to 14 after first infusion in study
measure: Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (tmax)
timeFrame: Time period including days 1 to 14 after first infusion in study
measure: Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (t1/2)
timeFrame: Time period including days 1 to 14 after first infusion in study
measure: Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (λZ)
timeFrame: Time period including days 1 to 14 after first infusion in study
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on occurrence of adverse events
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on blood pressure
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on body temperature
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on respiratory rate
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hematocrit
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hemoglobin
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter white blood cells
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter platelet count
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter alanine aminotransferase
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter aspartate aminotransferase
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter creatinine
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter Blood Urea Nitrogen (BUN)
timeFrame: 26 weeks
measure: Evaluate descriptively the safety and tolerability of OctaAlpha1 based on viral safety (HAV, HBV, HCV, HIV-1/2, HN, and parvovirus B19)
timeFrame: 26 weeks
measure: Trough Levels of A1PI
timeFrame: 26 weeks
measure: Pharmacodynamics of OctaAlpha1 measuring Pulmonary function tests
timeFrame: 26 weeks
measure: 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.
timeFrame: 26 weeks
measure: 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.
timeFrame: 26 weeks
measure: Investigate the pharmacodynamics of OctaAlpha1 measuring antibodies to A1PI using normal ranges of the central laboratory
timeFrame: 26 weeks
measure: Determine PK parameters of the A1PI serum concentration versus time curve following a single dose of OctaAlpha1
timeFrame: 26 weeks
Other outcomes:
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