Clinical trial NCT04440488: ARALAST NP Alpha-1 Lung Density Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E) Study
Official title: A Prospective, Randomized, Double-Blind, Parallel Group Study to Evaluate the Safety and Efficacy of ARALAST NP 60 mg/kg and 120 mg/kg for Alpha-1 Proteinase Inhibitor (A1PI) Augmentation Therapy in Subjects With A1PI Deficiency and Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Alpha1-antitrypsin Deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-06-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
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 evaluate the efficacy of ARALAST NP A1PI augmentation therapy 120 milligrams per kilogram (mg/kg) body weight (BW)/week compared with an external placebo comparator on the loss of emphysematous lung tissue measured by lung density change in participants with A1PI deficiency and COPD-E.


Eligibility criteria: Inclusion Criteria:

* Adults 18 to 65 years of age at the time of screening
* Diagnosis of A1PI deficiency with endogenous plasma A1PI level less than (\<) 11 micromoles(μM) (\< 0598 milligram per milliliter \[mg/mL\]) following 4-week minimum washout from previous last dose of A1PI augmentation therapy The screening plasma A1PI level may be repeated if a participant is determined to have an exclusionary value that maybe due to an inadequate washout of augmentation therapy Participants eligible for enrollment include newly diagnosed, previously untreated, currently treated and currently not on treatment but received treatment in the past
* Participants should have a documented A1PI genotype and if not, A1PI genotyping will be offered at the time of screening The purpose for genotyping is for sub-group analysis of study results only
* Clinically evident COPD-E (according to GOLD criteria (2020) for diagnosis, Stage I-III) (Global Initiative for Chronic Obstructive Lung Disease \[COPD\]) at the time of screening defined as follows: Forced expiratory volume in 1 second (FEV1) is greater than or equal to (\>or=) 35% and less than or equal to (\<or=) 70% predicted
* If treated with any respiratory medications including inhaled bronchodilators, inhaled corticosteroids, or systemic corticosteroids (example \[eg\] prednisone \<or= 10 milligram per day \[mg/day\] or its equivalent), the doses of medications should have remained stable for at least 28 days prior to screening
* No clinically significant abnormalities (other than emphysema, bronchitis or bronchiectasis) detected via chest CT at the time of screening
* Males and non-pregnant, non-lactating females whose screening pregnancy test is negative and willing and able to employ adequate contraceptive methods deemed reliable by the investigator for the duration of the study
* Willing and able to refrain from smoking (including e-cigarettes and vaping of any other substance) for the duration of study
* Willing and able to comply with the requirements of the protocol and able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) an informed consent to participate in the study

Exclusion Criteria:

* Known ongoing or history of clinically significant disease other than respiratory or liver disease secondary to AATD
* If experiencing corona virus diease (COVID)-19, lower respiratory tract infection (LRTI) and/or acute COPD exacerbation at the time of screening. Participant may be re-screened after clinical resolution of COVID-19, LRTI and/or acute COPD exacerbation and having also remained stable for at least 6 weeks after resolution
* Known ongoing or history of clinically significant cor pulmonale and/or congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms
* Has received an organ transplant, has undergone major lung surgery (eg, lung volume reduction surgery or lobectomy surgery), or is currently on a transplant waiting list
* 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, or stable prostate cancer not requiring treatment)
* Current active smoker (including e-cigarettes or vaping, nicotine or any other substance). A participant with a previous history of smoking has to have ceased active smoking at least 6 months prior to screening. Participants with a positive nicotine/cotinine test due to nicotine replacement therapy (eg, patches, chewing gum) or snuff are eligible
* Receiving long-term therapy (\> 28 days) of parenteral corticosteroids or oral corticosteroids at doses greater than 10 mg/day of prednisone or its equivalent
* Receiving chronic 24 hours/day oxygen supplementation (other than for an acute COPD exacerbation, or supplemental oxygen with continuous positive airway pressure \[CPAP\], or bi-level positive airway pressure \[BiPAP\] for acute respiratory failure)
* Known selective immunoglobulin A (IgA) deficiency (IgA level \< 7 milligrams per deciliter \[mg/dL\] at screening) with anti-IgA antibodies and a history of hypersensitivity reaction
* Known history of hypersensitivity following infusions of human immunoglobulins, human albumin, blood or blood components
* Presence of clinically significant laboratory abnormalities at the screening that in the opinion of the investigator would impact the participant's safety, if enrolled in the study
* Presence of any of the following that in the opinion of the investigator, would affect participant's safety or compliance or confound the results of the study, including known 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)
* Known exposure 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
* Participant is a family member or employee of the investigator
* If female, participant is pregnant or nursing at the time of enrollment

Primary outcomes:
measure: Annual Rate of the Physiologically Adjusted Lung Density Change
timeFrame: Baseline, up to Week 104
Secondary outcomes:
measure: Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: Baseline, up to Week 104
measure: Annual Rate of Change in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline, up to Week 104
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAE's)
timeFrame: From Start of the study drug administration up to End of the study (up to Week 105)
measure: Number of Participants Who Develop Anti-A1PI Antibodies Following Treatment With ARALAST NP
timeFrame: From Start of the study drug administration up to End of the study (up to Week 105)
measure: Plasma Trough Level of Antigenic and Functional A1PI for ARALAST NP at each dose Level
timeFrame: Pre-dose, Weeks 4, 13, 28, 52, 78, 91, 104, 105
Other outcomes:
Locations:
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: