Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency

Brief Title

Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency

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)

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).
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Rate of Change in Lung Density Based on Group 1 (ARALAST NP) Versus Placebo, Group 3 and Group 4 (GLASSIA) Versus Placebo

Secondary Outcome

 Rate of Change in Lung Density for Each Treatment Group

Condition

Chronic Obstructive Pulmonary Disease

Intervention

ARALAST NP 60 mg/kg

Study Arms / Comparison Groups

 ARALAST NP 60 mg/kg

Description:  60 mg/kg body weight/week

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

7

Start Date

November 2, 2016

Completion Date

September 14, 2018

Primary Completion Date

September 14, 2018

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Study Director, , 

Location Countries

Australia

Location Countries

Australia

NCT ID

NCT02722304

Organization ID

460503

Responsible Party

Sponsor

Study Sponsor

Baxalta now part of Shire

Collaborators

 Baxalta Innovations GmbH, now part of Shire

Study Sponsor

Study Director, Study Director, Takeda

Verification Date

April 2021