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

Primary Purpose

Alpha 1-Antitrypsin Deficiency

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

OctaAlpha1

Glassia

About this trial

This is an interventional treatment trial for Alpha 1-Antitrypsin Deficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

OctaAlpha1

Glassia®

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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%.

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%

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)

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)

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)

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

Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse

Evaluate descriptively the safety and tolerability of OctaAlpha1 based on body temperature

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

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

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

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

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 hepatic parameter alanine aminotransferase

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

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

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)

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)

Trough Levels of A1PI

Investigate descriptively the trough levels of A1PI and anti-NE capacity of OctaAlpha1 compared to Glassia®

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)

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.

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

Full Information

NCT ID

NCT03385395

First Posted

December 1, 2017

Last Updated

April 6, 2018

Sponsor

Octapharma

1. Study Identification

Unique Protocol Identification Number

NCT03385395

Brief Title

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

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Withdrawn

Why Stopped

IND has been closed.

Study Start Date

July 2018 (Anticipated)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Octapharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alpha 1-Antitrypsin Deficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

OctaAlpha1

Arm Type

Experimental

Arm Title

Glassia®

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

OctaAlpha1

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Glassia

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

26 weeks

Secondary Outcome Measure Information:

Title

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

Description

Time Frame