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Trial record 7 of 75 for:    "alpha-1 antitrypsin deficiency"

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

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ClinicalTrials.gov Identifier: NCT03385395
Recruitment Status : Withdrawn (IND has been closed.)
First Posted : December 28, 2017
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
Octapharma

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 Type : Interventional  (Clinical Trial)
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
Estimated Study Start Date : July 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


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




Primary Outcome Measures :
  1. Non-inferiority of OctaAlpha1 compared to Glassia® in terms of the serum trough levels at steady state [ Time Frame: 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 Frame: 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 Frame: 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 Frame: 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 Frame: 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 Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 26 weeks ]
    Determine PK parameters of the A1PI serum concentration versus time curve following a single dose of OctaAlpha1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT03385395     History of Changes
Other Study ID Numbers: OctaAlpha1
First Posted: December 28, 2017    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
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
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action