Clinical trial NCT02722304: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Alpha1-antitrypsin Deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2016-03-30
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Rate of Change in Lung Density Based on Group 1 (ARALAST NP) Versus Placebo, Group 3 and Group 4 (GLASSIA) Versus Placebo
timeFrame: Baseline, Early termination of the study (approximately 22 months)
Secondary outcomes:
measure: Rate of Change in Lung Density for Each Treatment Group
timeFrame: Baseline, Early termination of the study (approximately 22 months)
measure: Mean Steady State Trough Concentration of Antigenic and Functional Alpha1-Proteinase Inhibitor (A1PI) for ARALAST NP and GLASSIA at Each Dose Level
timeFrame: Baseline, Early termination of the study (approximately 22 months)
measure: Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE)
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's)
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs)
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs)
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs)
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs)
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs
timeFrame: From start of study treatment up to early termination of the study (approximately 22 months)
measure: Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA
timeFrame: Baseline, Early termination of the study (approximately 22 months)
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Phoenix Medical Research Institute, LLC
state: Arizona
city: Newport Beach
country: United States
facility: Newport Native MD, Inc
state: California
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists, P.A., / PDS Research
state: Florida
city: Miami
country: United States
facility: L&C Professional Medical Research Institute
state: Florida
city: Maywood
country: United States
facility: Loyola University Health System
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Michigan City
country: United States
facility: La Porte County Institute for Clinical Research, Inc.
state: Indiana
city: Fayetteville
country: United States
facility: Pulmonary Health Physicians
state: New York
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center LLC
state: North Carolina
city: Allen
country: United States
facility: Metroplex Pulmonary and Sleep Center
state: Texas
city: Houston
country: United States
facility: Houston Pulmonary and Sleep Associates
state: Texas
city: San Antonio
country: United States
facility: Element Research Group
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical-Respiratory & Sleep Disorders Specialists
state: Texas
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: