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

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

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 Overview

• Status: Withdrawn
• Conditions: Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: OctaAlpha1; Drug: Glassia

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OctaAlpha1	Drug: OctaAlpha1; For OctaAlpha1 the standard weekly dose of 60mg/kg will be given for 24 consecutive infusions
Active Comparator: Glassia®	Drug: Glassia; For Glassia the standard weekly dose of 60mg/kg will be given for 24 consecutive infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state	Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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%.	Time period including days 1 to 14 after first infusion in study
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (Cmax)	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%	Time period including days 1 to 14 after first infusion in study
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (tmax)	Compare PK parameters following a single dose between the two treatment groups calculating tmax (time to reach maximum serum concentration)	Time period including days 1 to 14 after first infusion in study
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (t1/2)	Compare PK parameters following a single dose between the two treatment groups calculating t1/2 (apparent terminal half-life)	Time period including days 1 to 14 after first infusion in study
Compare PK parameters following a single dose between the two treatment groups following principles of bio-equivalence testing (λZ)	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)	Time period including days 1 to 14 after first infusion in study
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on occurrence of adverse events	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 blood pressure	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on blood pressure	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on body temperature	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on body temperature	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on respiratory rate	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on respiratory rate	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hematocrit	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hematocrit via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hemoglobin	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter hemoglobin via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter white blood cells	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter white blood cells via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter platelet count	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hematological parameter platelet count via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter alanine aminotransferase	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter alanine aminotransferase via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter aspartate aminotransferase	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring hepatic parameter aspartate aminotransferase via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter creatinine	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter creatinine via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter Blood Urea Nitrogen (BUN)	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on monitoring renal parameter Blood Urea Nitrogen (BUN) via lab test	26 weeks
Evaluate descriptively the safety and tolerability of OctaAlpha1 based on viral safety (HAV, HBV, HCV, HIV-1/2, HN, and parvovirus B19)	Evaluate descriptively the safety and tolerability of OctaAlpha1 based on viral safety (HAV, HBV, HCV, HIV-1/2, HN, and parvovirus B19)	26 weeks
Trough Levels of A1PI	Investigate descriptively the trough levels of A1PI and anti-NE capacity of OctaAlpha1 compared to Glassia®	26 weeks
Pharmacodynamics of OctaAlpha1 measuring Pulmonary function tests	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)	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 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 LTB4 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 antibodies to A1PI using normal ranges of the central laboratory	Investigate the pharmacodynamics of OctaAlpha1 measuring antibodies to A1PI using normal ranges of the central laboratory	26 weeks
Determine PK parameters of the A1PI serum concentration versus time curve following a single dose of OctaAlpha1	Determine PK parameters of the A1PI serum concentration versus time curve following a single dose of OctaAlpha1	26 weeks

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 28, 2017

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 6, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: OctaAlpha1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No