Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency

NCT ID: NCT02722304

Last Updated: 2021-05-13

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-02

Study Completion Date

2018-09-14

Brief Summary

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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).

Detailed Description

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Conditions

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Chronic Obstructive Pulmonary Disease Alpha1-antitrypsin Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ARALAST NP 60 mg/kg

60 mg/kg body weight/week

Group Type EXPERIMENTAL

ARALAST NP 60 mg/kg

Intervention Type BIOLOGICAL

ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

ARALAST NP 120 mg/kg

120 mg/kg body weight/week

Group Type EXPERIMENTAL

ARALAST NP 120 mg/kg

Intervention Type BIOLOGICAL

ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

GLASSIA 60 mg/kg

60 mg/kg body weight/week

Group Type EXPERIMENTAL

GLASSIA 60 mg/kg

Intervention Type BIOLOGICAL

GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

GLASSIA 120 mg/kg

120 mg/kg body weight/week

Group Type EXPERIMENTAL

GLASSIA 120 mg/kg

Intervention Type BIOLOGICAL

GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

Placebo

Human Albumin 2%

Group Type PLACEBO_COMPARATOR

Human Albumin 2%

Intervention Type BIOLOGICAL

Human albumin 2% (by appropriate dilution with normal saline solution)

Interventions

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ARALAST NP 60 mg/kg

ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

Intervention Type BIOLOGICAL

ARALAST NP 120 mg/kg

ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

Intervention Type BIOLOGICAL

GLASSIA 60 mg/kg

GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

Intervention Type BIOLOGICAL

GLASSIA 120 mg/kg

GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy

Intervention Type BIOLOGICAL

Human Albumin 2%

Human albumin 2% (by appropriate dilution with normal saline solution)

Intervention Type BIOLOGICAL

Other Intervention Names

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Alpha1-Proteinase Inhibitor (Human) A1PI Alpha1-Proteinase Inhibitor Alpha1-Proteinase Inhibitor Alpha1-Proteinase Inhibitor (Human) A1PI Alpha1-Proteinase Inhibitor (Human) A1PI Alpha1-Proteinase Inhibitor Alpha1-Proteinase Inhibitor Alpha1-Proteinase Inhibitor (Human) A1PI

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Baxalta Innovations GmbH, now part of Shire

INDUSTRY

Sponsor Role collaborator

Baxalta now part of Shire

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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Phoenix Medical Research Institute, LLC

Peoria, Arizona, United States

Site Status

Newport Native MD, Inc

Newport Beach, California, United States

Site Status

Pulmonary Disease Specialists, P.A., / PDS Research

Kissimmee, Florida, United States

Site Status

L&C Professional Medical Research Institute

Miami, Florida, United States

Site Status

Loyola University Health System

Maywood, Illinois, United States

Site Status

Indiana University Health

Indianapolis, Indiana, United States

Site Status

La Porte County Institute for Clinical Research, Inc.

Michigan City, Indiana, United States

Site Status

Pulmonary Health Physicians

Fayetteville, New York, United States

Site Status

Clinical Research of Gastonia

Gastonia, North Carolina, United States

Site Status

Southeastern Research Center LLC

Winston-Salem, North Carolina, United States

Site Status

Metroplex Pulmonary and Sleep Center

Allen, Texas, United States

Site Status

Houston Pulmonary and Sleep Associates

Houston, Texas, United States

Site Status

Element Research Group

San Antonio, Texas, United States

Site Status

Renovatio Clinical-Respiratory & Sleep Disorders Specialists

The Woodlands, Texas, United States

Site Status

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status

LHSC - Victoria Hospital

London, Ontario, Canada

Site Status

Inspiration Research Limited

Toronto, Ontario, Canada

Site Status

Countries

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United States Australia Canada

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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460503

Identifier Type: -

Identifier Source: org_study_id

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