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

• Sponsor: Octapharma (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT03385395
• Collaborator: (none)
• Enrollment: 0
• Arms: 2
• Anticipated Duration (Months): 17

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Alpha 1-Antitrypsin Deficiency	Drug: OctaAlpha1; Drug: Glassia	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Jul 1, 2018
• Anticipated Primary Completion Date: Dec 1, 2019
• Anticipated Study Completion Date: Dec 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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%.

2. 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%

3. 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)

4. 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)

5. 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)

6. 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

7. 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

8. Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse [26 weeks]

   Evaluate descriptively the safety and tolerability of OctaAlpha1 based on pulse

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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)

20. Trough Levels of A1PI [26 weeks]

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

21. 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)

22. 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.

23. 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.

24. 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

25. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Octapharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Octapharma
• ClinicalTrials.gov Identifier: NCT03385395
• Other Study ID Numbers: OctaAlpha1
• First Posted: Dec 28, 2017
• Last Update Posted: Apr 10, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Additional relevant MeSH terms: Alpha 1-Antitrypsin Deficiency; Alpha 1-Antitrypsin

Study Results

No Results Posted as of Apr 10, 2018