Chronic Obstructive Pulmonary DiseasePhase 4NCT04440488
ARALAST NP Alpha-1 Lung Density Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E) Study
A Phase 4 study testing ARALAST NP in people with Chronic Obstructive Pulmonary Disease and Alpha1-antitrypsin Deficiency, run by Shire.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease, Alpha1-antitrypsin Deficiency
- What is being tested?
- ARALAST NP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 8 Mar 2021to 12 Sep 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
About this 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)
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.
- Being tested
- ARALAST NP
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARALAST NPBiological
Also called Alpha1-PI, TAK-883, A1PI, Alpha1-Proteinase Inhibitor (Human)
Partcipants will be randomized to receive ARALAST NP 60 or 120 mg/kg BW/week IV infusion for a total of 104 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: ARALAST NP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, up to Week 104
Secondary outcomes (5)
Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
COPD exacerbations are defined as an acute worsening of respiratory symptoms that results in additional therapy and will be assessed according to the classification in GOLD criteria (2020) as follows: Moderate (treated with short acting bronchodilators [SABDs] plus antibiotics and/or oral corticosteroids) and Severe (required hospitalizations or a visit to the emergency room).
Measured: Baseline, up to Week 104
Annual Rate of Change in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Annual rate of change in post-bronchodilator FEV1 will be assessed.
Measured: Baseline, up to Week 104
Number of Participants with Treatment-Emergent Adverse Events (TEAE's)
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this IP or medicinal product. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. TEAE's will include related, serious adverse events (SAEs), suspected adverse reactions plus adverse reactions of interest, temporally-associated adverse events (AEs) with onset during infusion or within 24 hours following the end of IP infusion, and AEs resulting in changes to infusion dose.
Measured: 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
Number of participants who develop anti- A1PI antibodies following treatment with ARALAST NP will be assessed.
Measured: 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
Plasma trough level of antigenic and functional A1PI for ARALAST NP at each dose level (ARALAST NP 60 mg/kg BW/week, ARALAST NP 120 mg/kg BW/week) will be assessed.
Measured: Pre-dose, Weeks 4, 13, 28, 52, 78, 91, 104, 105
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2020
- Study start8 Mar 2021 (estimated)
- Primary completion12 Sep 2025 (estimated)
- Study completion12 Sep 2025 (estimated)
Why it stopped: Reevaluation of development strategy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04440488
- Sponsor's protocol ID
- TAK-883-3001
- Status last verified
- Sep 2020
- First submitted
- 17 Jun 2020
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04440488
- Acronym / sponsor ID
- TAK-883-3001
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Reevaluation of development strategy
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2021 (estimated)
- Primary completion
- 12 Sep 2025 (estimated)
- Study completion
- 12 Sep 2025 (estimated)
- First posted
- 19 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARALAST NP 120 mg/kg | Experimental | Biological: ARALAST NPParticipants 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. |
| ARALAST NP 60 mg/kg | Experimental | Biological: ARALAST NPParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARALAST NPAlso: Alpha1-PI, TAK-883, A1PI, Alpha1-Proteinase Inhibitor (Human)Partcipants will be randomized to receive ARALAST NP 60 or 120 mg/kg BW/week IV infusion for a total of 104 weeks. | Biological | ARALAST NP 120 mg/kg, ARALAST NP 60 mg/kg |
Primary outcome
Annual Rate of the Physiologically Adjusted Lung Density Change
Time frame: Baseline, up to Week 104
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.
5 secondary outcomes
Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
Time frame: Baseline, up to Week 104
Annual Rate of Change in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline, up to Week 104
Number of Participants with Treatment-Emergent Adverse Events (TEAE's)
Time frame: 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
Time frame: 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
Time frame: Pre-dose, Weeks 4, 13, 28, 52, 78, 91, 104, 105
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2020.
- Individual participant dataSharing planned: Yes. Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Shire
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ARALAST NP in people with Chronic Obstructive Pulmonary Disease and Alpha1-antitrypsin Deficiency, run by Shire.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual Rate of the Physiologically Adjusted Lung Density Change (time frame: Baseline, up to Week 104). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2020.