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Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency

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ClinicalTrials.gov Identifier: NCT02722304
Recruitment Status : Terminated
First Posted : March 30, 2016
Last Update Posted : November 26, 2018
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
The purpose of this study is to conduct a pilot study to evaluate the safety and efficacy of weekly administration of Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy in subjects with A1PI deficiency and emphysema/ chronic obstructive pulmonary disease (COPD).

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Alpha1-antitrypsin Deficiency Biological: ARALAST NP 60 mg/kg Biological: ARALAST NP 120 mg/kg Biological: GLASSIA 60 mg/kg Biological: GLASSIA 120 mg/kg Biological: Human Albumin 2% Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Stage 1, Prospective, Randomized, Placebo-Controlled, Double- Blind Study to Evaluate the Safety and Efficacy of Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Subjects With A1PI Deficiency and Chronic Obstructive Pulmonary Disease (COPD)
Actual Study Start Date : November 2, 2016
Actual Primary Completion Date : September 14, 2018
Actual Study Completion Date : September 14, 2018


Arm Intervention/treatment
Experimental: ARALAST NP 60 mg/kg
60 mg/kg body weight/week
Biological: ARALAST NP 60 mg/kg
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Other Names:
  • Alpha1-Proteinase Inhibitor (Human)
  • A1PI
  • Alpha1-Proteinase Inhibitor

Experimental: ARALAST NP 120 mg/kg
120 mg/kg body weight/week
Biological: ARALAST NP 120 mg/kg
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Other Names:
  • Alpha1-Proteinase Inhibitor
  • Alpha1-Proteinase Inhibitor (Human)
  • A1PI

Experimental: GLASSIA 60 mg/kg
60 mg/kg body weight/week
Biological: GLASSIA 60 mg/kg
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Other Names:
  • Alpha1-Proteinase Inhibitor (Human)
  • A1PI
  • Alpha1-Proteinase Inhibitor

Experimental: GLASSIA 120 mg/kg
120 mg/kg body weight/week
Biological: GLASSIA 120 mg/kg
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Other Names:
  • Alpha1-Proteinase Inhibitor
  • Alpha1-Proteinase Inhibitor (Human)
  • A1PI

Placebo Comparator: Placebo
Human Albumin 2%
Biological: Human Albumin 2%
Human albumin 2% (by appropriate dilution with normal saline solution)




Primary Outcome Measures :
  1. Rate of change in lung density for (1) all ARALAST NP recipients versus placebo recipients; and (2) all GLASSIA recipients versus placebo recipients [ Time Frame: Weeks 1, 26, 52, 78, and 104; and early termination visit- if last assessment >13 weeks prior to the early termination visit. ]
    Assessed by computed tomography (CT) densitometry


Secondary Outcome Measures :
  1. Rate of change in lung density for each treatment group [ Time Frame: Weeks 1, 26, 52, 78, and 104; and early termination visit- if last assessment >13 weeks prior to the early termination visit. ]
    Assessed by computed tomography (CT) densitometry for each treatment group: ie ARALAST NP 60 mg/kg, ARALAST NP 120 mg/kg, GLASSIA 60 mg/kg, GLASSIA 120 mg/kg, and placebo (Albumin 2%, 6mL/kg)

  2. Mean steady state trough concentration of antigenic and functional Alpha1-Proteinase Inhibitor (A1PI) for ARALAST NP and GLASSIA at each dose level [ Time Frame: Antigenic A1PI baseline; and antigenic and functional A1PI at week 1, 13, 26, 39, 52, 65, 78, 91, 104, 105, and early termination visit (if applicable). ]
  3. Number of related and unrelated serious and non-serious adverse events (AEs) [ Time Frame: Throughout the study period of approximately 4 years ]
  4. Rate of related and unrelated serious and non-serious adverse events (AEs) [ Time Frame: Throughout the study period of approximately 4 years ]
  5. Number of temporally related serious and non-serious adverse events (AEs) [ Time Frame: Throughout the study period of approximately 4 years ]
    Temporally related = serious and non-serious AEs which began during or within 72 hours following the end of IP infusion

  6. Rate of temporally related serious and non-serious adverse events (AEs) [ Time Frame: Throughout the study period of approximately 4 years ]
    Temporally related = serious and non-serious AEs which began during or within 72 hours following the end of IP infusion

  7. Number of suspected adverse reactions and adverse reactions (ARs) [ Time Frame: Throughout the study period of approximately 4 years ]
  8. Rate of suspected adverse reactions and adverse reactions (ARs) [ Time Frame: Throughout the study period of approximately 4 years ]
  9. Number of infusions for which the infusion rate was reduced and/or the infusion interrupted or stopped due to adverse events (AEs) [ Time Frame: Throughout the study period of approximately 4 years ]
  10. Number of participants who develop anti-A1PI antibodies following treatment with ARALAST NP or GLASSIA [ Time Frame: Throughout the study period of approximately 4 years ]


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:

  1. ≥18 years of age at the time of screening
  2. Endogenous plasma Alpha1-Proteinase Inhibitor (A1PI) level <8 μM at any time during the Screening period for treatment-naïve participants, or following 4-weeks minimum wash-out from previous augmentation therapy in treatment-experienced participants. The screening plasma A1PI level may be repeated if a participant obtains an exclusionary value that is suspected to be due to inadequate washout of A1PI).
  3. Participant has documented A1PI genotype of Pi*Z/Z, Pi*Z/Null, Pi*Malton/Z, Pi*Null/Null, or other rare genotypes (except PI*MS, PI*MZ, or PI*SZ).
  4. Clinically evident mild-moderate chronic obstructive pulmonary disease (COPD) (according to GOLD criteria for diagnosis) at the time of screening.
  5. If the participant is treated with any respiratory medications including inhaled bronchodilators, inhaled corticosteroids, or systemic corticosteroids (e.g. prednisone ≤ 10 mg/day or its equivalent), the doses of the participant's medications have remained stable for at least 28 days prior to screening.
  6. No clinically significant abnormalities (other than emphysema, bronchitis or bronchiectasis) detected via a chest computed tomography (CT) or chest X-ray at the time of screening.
  7. If female of childbearing potential, participant must have a negative pregnancy test at screening and agree to employ adequate birth control measures for the duration of the study.
  8. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

  1. Known ongoing or history of clinically significant pulmonary impairment other than emphysema/ COPD.
  2. The participant is experiencing lower respiratory infection (LRTI)/acute pulmonary exacerbation (APE) at the time of enrollment (signing Informed consent form (ICF)). Participant may be rescreened after both clinical resolution of LRTI/APE and having also remained stable for at least 4 weeks after the end of LRTI/APE).
  3. Known ongoing or history of cor pulmonale.
  4. Known resting partial pressure of carbon dioxide (PaCO2) levels of > 45 mmHg.
  5. Clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
  6. The participant has received an organ transplant, has undergone major lung surgery, or is currently on a transplant list.
  7. Known history of ongoing malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix).
  8. Smoker or participant that has ceased smoking for less than one year prior to screening whose levels of cotinine are outside of the normal range of a nonsmoker.

    All participants must agree to refrain from smoking throughout the course of the study.

  9. The participant is receiving long-term therapy (> 28 days) of parenteral corticosteroids or oral corticosteroids at doses greater than 10 mg/day of prednisone or its equivalent).
  10. The participant is receiving long-term round-the-clock oxygen supplementation (other than temporary for acute COPD exacerbation, or supplemental oxygen (O2) with continuous positive airway pressure [CPAP], or bi-level positive airway pressure [BiPAP] during the day).
  11. Participant has contraindications for CT (e.g. body weight and/or body size exceeding the weight and gantry size limits specified by the manufacturer of the CT scanner, inability to lie flat in the CT scanner, claustrophobia, metal prosthesis or pacemaker in the chest wall or upper extremity that would impact lung density assessment).
  12. Participant is unwilling or unable to modify bronchodilator medications for 6 hours for short acting β2 agonists, 24 hours for long-acting β2 agonists, and 48 hours for long acting anticholinergics prior to the scheduled quantitative CT scan.
  13. Known severe immunoglobulin A (IgA) deficiency (ie, IgA level < 8 mg/dL at screening).
  14. Known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin).
  15. Presence of clinically significant laboratory abnormalities at the screening
  16. The participant has a clinically significant medical, psychiatric, or cognitive illness, is a recreational drug/alcohol user, or has any other uncontrolled medical condition (eg, unstable angina, transient ischemic attack, uncontrolled hypertension) that, in the opinion of the investigator, would affect participant's safety or compliance or confound the results of the study.
  17. Participant has been exposed to another IP within 28 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
  18. Participant is a family member or employee of the investigator.
  19. If female, participant is pregnant or nursing at the time of enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02722304


Locations
United States, Arizona
Phoenix Medical Research Institute, LLC
Peoria, Arizona, United States, 85381
United States, California
Newport Native MD, Inc
Newport Beach, California, United States, 92663
United States, Florida
Pulmonary Disease Specialists, P.A., / PDS Research
Kissimmee, Florida, United States, 34741
L&C Professional Medical Research Institute
Miami, Florida, United States, 33144
United States, Illinois
Loyola University Health System
Maywood, Illinois, United States, 60153
United States, Indiana
Indiana University Health
Indianapolis, Indiana, United States, 46202
La Porte County Institute for Clinical Research, Inc.
Michigan City, Indiana, United States, 46360
United States, New York
Pulmonary Health Physicians
Fayetteville, New York, United States, 13066
United States, North Carolina
Clinical Research of Gastonia
Gastonia, North Carolina, United States, 28054
Southeastern Research Center LLC
Winston-Salem, North Carolina, United States, 27103
United States, Texas
Metroplex Pulmonary and Sleep Center
Allen, Texas, United States, 75013
Houston Pulmonary and Sleep Associates
Houston, Texas, United States, 77065
Element Research Group
San Antonio, Texas, United States, 78258
Renovatio Clinical-Respiratory & Sleep Disorders Specialists
The Woodlands, Texas, United States, 77005
Australia, Victoria
St Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia, 34741
Canada, Ontario
LHSC - Victoria Hospital
London, Ontario, Canada, N6A 5W9
Inspiration Research Limited
Toronto, Ontario, Canada, M5T 3A9
Sponsors and Collaborators
Baxalta now part of Shire
Baxalta Innovations GmbH, now part of Shire
Investigators
Study Director: Study Director Shire

Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02722304     History of Changes
Other Study ID Numbers: 460503
First Posted: March 30, 2016    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Alpha 1-Antitrypsin Deficiency
Respiratory Tract Diseases
Liver Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Protease Inhibitors
Alpha 1-Antitrypsin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors