ARALAST NP Alpha-1 Lung Density Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E) Study

NCT04440488 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: TAK-883-3001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Obstructive Pulmonary Disease; Alpha1-antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• Annual Rate of the Physiologically Adjusted Lung Density Change

  Annual rate of the physiologically adjusted lung density change will be measured as the 15th percentile of the lung density measurements (PD15) as assessed by Computed Tomography (CT) densitometry at total lung capacity (TLC). CT lung density at the 15th percentile (PD15) is the threshold below which 15 percentage (%) of the voxels have lower densities and is used as the parameter for estimating the rate of lung density decline. Annual rate of the physiologically adjusted lung density change will be tested in a fixed comparision sequence 1. ARALAST NP 120 mg/kg BW/week group versus (vs) external placebo group, 2. ARALAST NP120 mg/kg BW/week vs 60 mg/kg BW/week, 3. ARALAST NP 60 mg/kg BW/week group vs external placebo group.

  Baseline, up to Week 104

Secondary Outcomes (5)

• Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

  Baseline, up to Week 104

• Annual Rate of Change in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)

  Baseline, up to Week 104

• Number of Participants with Treatment-Emergent Adverse Events (TEAE's)

  From Start of the study drug administration up to End of the study (up to Week 105)

• Number of Participants Who Develop Anti-A1PI Antibodies Following Treatment With ARALAST NP

  From Start of the study drug administration up to End of the study (up to Week 105)

• Plasma Trough Level of Antigenic and Functional A1PI for ARALAST NP at each dose Level

  Pre-dose, Weeks 4, 13, 28, 52, 78, 91, 104, 105

Study Arms (2)

ARALAST NP 120 mg/kg

EXPERIMENTAL

Participants will receive 120 mg/kg BW of ARALAST NP intravenous (IV) infusion once in a week for a total of 104 weeks which will be compared with an external placebo arm.

Biological: ARALAST NP

ARALAST NP 60 mg/kg

EXPERIMENTAL

Participants will receive 60 mg/kg BW of ARALAST NP IV infusion once in a week for a total of 104 weeks which will be compared with an external placebo arm.

Biological: ARALAST NP

Interventions

ARALAST NP BIOLOGICAL

Partcipants will be randomized to receive ARALAST NP 60 or 120 mg/kg BW/week IV infusion for a total of 104 weeks.

Also known as: Alpha1-PI, TAK-883, A1PI, Alpha1-Proteinase Inhibitor (Human)

ARALAST NP 120 mg/kg; ARALAST NP 60 mg/kg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 to 65 years of age at the time of screening
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; alpha 1-Antitrypsin Deficiency

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: June 19, 2020
• Study Start: March 8, 2021
• Primary Completion: September 12, 2025
• Study Completion: September 12, 2025
• Last Updated: September 14, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.