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Chronic Obstructive Pulmonary Disease (COPD)Phase 4NCT05466747

A Study of RYMPHYSIA for Alpha1-Proteinase Inhibitor (A1PI) Therapy in Adults With A1PI Deficiency and Chronic Obstructive Pulmonary Disease (COPD)-Emphysema

A Phase 4 study testing RYMPHYSIA and Another Available A1PI in people with Chronic Obstructive Pulmonary Disease (COPD) and Alpha1-Antitrypsin Deficiency, run by Takeda.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The main purpose of this study is to evaluate the efficacy of RYMPHYSIA [Alpha1-Proteinase Inhibitor (Human)] compared to another available alpha-1 proteinase Inhibitor (A1PI) in adults with A1PI deficiency and COPD-emphysema. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
RYMPHYSIA and Another Available A1PI
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
1 Jan 2024to 7 May 2029
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult 18 to 75 years at the time of screening.
  • Diagnosis of alpha1-proteinase inhibitor (A1PI) deficiency, defined as follows:
  • Endogenous serum A1PI level lesser than (<)11 micromolar (μM) or 57.2 micrograms per deciliter (mg/dL) (0.572 gram per liter [g/L]) (as measured at the end of the washout, if applicable)
  • Genotype ZZ, Z/null, null/null, MMalton/Z, or others that result in A1PI levels <11 μM. Prior documentation of genotype will be sufficient, or genotyping will be offered at the time of screening
  • Participants eligible for enrollment include newly diagnosed, previously untreated, currently treated, and currently not on treatment but who have received treatment in the past. For those currently on augmentation therapy, a 2-week minimum washout is required until A1PI levels are <11 μM.
  • Clinically evident chronic obstructive pulmonary disease (COPD)-emphysema at the time of screening defined by post-bronchodilator FEV1 of greater than or equal to (≥)30 percent (%) and lesser than or equal to (≤)80% predicted and FEV1/forced vital capacity (FVC) <70%, corresponding to mild to severe COPD (according to Global Initiative for Chronic Obstructive Lung Disease [GOLD] Criteria, stage I-III) (Global Initiative for Chronic Obstructive Lung Disease 2021) and evidence of emphysema on chest imaging (confirmed by the baseline computer topography [CT] densitometry scan).
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  • If treated with any respiratory medications including inhaled bronchodilators, inhaled corticosteroids, or systemic corticosteroids (e.g., prednisone ≤10 micrograms 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 imaging 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.
  • 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) 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 A1PI deficiency.
  • If experiencing COVID-19, lower respiratory tract infection (LRTI) and/or acute COPD exacerbation at the time of screening. Participants may be re-screened after clinical resolution of COVID-19, LRTI and/or acute COPD exacerbation and must have also remained stable for at least 6 weeks after the onset of illness.
  • 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 (e.g., lung volume reduction surgery or lobectomy surgery), or is currently on a transplant waiting list.
  • Experiencing an active malignancy or has a history of malignancy within 5 years prior to screening, with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, 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 mg/dL at screening) with anti-IgA antibodies and a history of any 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 (e.g., unstable angina, transient ischemic attack, uncontrolled hypertension).
  • Known exposure to another investigational product/investigational medicinal product (IP/IMP) within 28 days prior to enrollment or is scheduled to participate in another clinical study involving an IP/IMP or investigational device during 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: Randomized, Open-label, Parallel-group, Multicenter, Non-inferiority and Dose-response Study to Evaluate the Efficacy and Safety of RYMPHYSIA (ARALAST NP) for Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Subjects With A1PI Deficiency and Chronic Obstructive Pulmonary Disease-Emphysema

The main purpose of this study is to evaluate the efficacy of RYMPHYSIA [Alpha1-Proteinase Inhibitor (Human)] compared to another available alpha-1 proteinase Inhibitor (A1PI) in adults with A1PI deficiency and COPD-emphysema.

In Part A of the study, participants will be randomly assigned to receive either RYMPHYSIA or another available A1PI for 104 weeks. Participants who were randomized to another available A1PI will enter a 2-week follow-up period after the treatment phase is completed; participants who were randomized to RYMPHYSIA will enter Part B.

In Part B, participants will be randomly assigned to one of two groups and will receive either the same dose of RYMPHYSIA as in Part A or a different dose for an additional 104 weeks, followed by a 2-week follow-up period.

Being tested
RYMPHYSIA, Another Available A1PI
Keywords
TAK-883, Chronic Obstructive Pulmonary Disease, RYMPHYSIA
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.

  • RYMPHYSIABiological

    Also called Alpha1-PI, TAK-883, A1PI, Alpha1-Proteinase Inhibitor (Human)

    RYMPHYSIA administered through an IV injection.

  • Another Available A1PIBiological

    Also called Alpha1-PI, Alpha1-Proteinase Inhibitor (Human)

    Another available A1PI administered through an IV injection.

Study groups in NCT05466747
Study groupRoleWhat they receive
Part A: RYMPHYSIA 60 mg/kgExperimentalParticipants will receive 60 mg/kg RYMPHYSIA, intravenous (IV) infusion, once every week for up to 104 weeks.
Receives: Biological: RYMPHYSIA
Part A: Another Available A1PI 60 mg/kgActive comparatorParticipants will receive 60 mg/kg of another available A1PI, IV infusion, once every week for up to 104 weeks.
Receives: Biological: Another Available A1PI
Part B: RYMPHYSIA 60 mg/kgExperimentalParticipants will receive 60 mg/kg RYMPHYSIA, IV infusion, once every week for up to 104 weeks.
Receives: Biological: RYMPHYSIA
Part B: RYMPHYSIA 120 mg/kgExperimentalParticipants will receive 120 mg/kg RYMPHYSIA, IV infusion, once every week for up to 104 weeks.
Receives: Biological: RYMPHYSIA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Annual Rate of Change in the Physiologically Adjusted Lung Density

    Annual rate of the physiologically adjusted lung density change will be measured as the 15th percentile (PD15) of the lung density measurements 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 percent (%) of the voxels have lower densities and is used as the parameter for estimating the rate of lung density decline.

    Measured: Up to Week 104

Secondary outcomes (15)

  1. Part A: Annual Rate of Change in the Plasma Level of Elastin Degradation Products

    The annual rate of change in the plasma levels of elastin degradation products (desmosine and isodesmosine) will be assessed to document the pharmacodynamic (PD) effect of RYMPHYSIA on the activity of neutrophil elastase using high-performance liquid chromatography-mass spectrometry (LC-MS). The assessment of elastin degradation products will be performed for participants in the RYMPHYSIA treatment arm only.

    Measured: Up to Week 104

  2. Part A: Annual Rate of Change in the Plasma Level of Fibrinogen Degradation Products

    The annual rate of change in the plasma levels of fibrinogen degradation products (Aα-Val360 fragments) will be assessed to document the PD effect of RYMPHYSIA on the activity of neutrophil elastase using high-performance LC-MS. The assessment of fibrinogen degradation products will be performed for participants in the RYMPHYSIA treatment arm only.

    Measured: Up to Week 104

  3. Part A and Part B: 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 based on the classification in GOLD criteria (2021). The assessment of COPD exacerbations will be performed for participants in the RYMPHYSIA treatment arm only.

    Measured: Part A, Part B: Up to Week 104

  4. Part A and Part B: Annual Rate of Change in the Post-bronchodilator Forced Expiratory Volume in One Second (FEV1)

    FEV1 is the volume of air that can be forcefully exhaled in the first second after a full inspiration obtained by spirometry. Annual rate of change in the FEV1 will be assessed using spirometry. Spirometric measurements are to be performed in triplicate, and the highest value at each time point is to be used for analyses.

    Measured: Part A, Part B: Up to Week 104

  5. Part A and Part B: Plasma Trough Level of Antigenic and Functional A1PI for RYMPHYSIA

    Measured: Part A, Part B: Pre- and post-dose at multiple timepoints (up to 144 hours) up to Week 104

  6. Part A and Part B: Plasma Concentration of Antigenic and Functional A1PI for RYMPHYSIA

    Measured: Part A, Part B: Pre- and post-dose at multiple timepoints (up to 144 hours) up to Week 104

  7. Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    The number of participants with TEAEs including drug-related AEs, serious AEs (SAEs), and temporally associated AEs will be assessed.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  8. Part A and Part B: Number of Participants Receiving RYMPHYSIA with Development of Post-treatment Immunogenicity as Measured by Anti-A1PI Binding and Neutralizing Antibodies

    Serum samples will be analyzed for the presence of antibodies against A1PI using a validated anti-A1PI antibody detection (screening and confirmatory) assay at a qualified specialty laboratory. Samples with confirmed positive titers will be further analyzed for the presence of neutralizing antibodies using a validated neutralizing antibody assay at a qualified specialty laboratory.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  9. Part A and Part B: Changes in Laboratory Assessments

    The number of participants who have normal/abnormal values at Baseline compared to normal/abnormal values post-Baseline will be assessed for hematology, clinical chemistry, and urinalysis.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  10. Part A and Part B: Changes in Vital Signs Measurement: Body Temperature

    Percent change from Baseline to post Baseline will be assessed for body temperature.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  11. Part A and Part B: Changes in Vital Signs Measurement: Respiratory Rate

    Percent change from Baseline to post Baseline will be assessed for respiratory rate.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  12. Part A and Part B: Changes in Vital Signs Measurement: Pulse Rate

    Percent change from Baseline to post Baseline will be assessed for pulse rate.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  13. Part A and Part B: Changes in Vital Signs Measurement: Systolic and Diastolic Blood Pressure

    Percent change from Baseline to post Baseline will be assessed for systolic and diastolic blood pressure.

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  14. Part A and Part B: Number of Participants with Changes in Electrocardiogram (ECG) Measurements

    Measured: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)

  15. Part B: Annual Rate of Change in the Physiologically Adjusted Lung Density

    The annual rate of the physiologically adjusted lung density change will be measured as the PD15 of the lung density measurements as assessed by CT densitometry at TLC. CT lung density at the PD15 is the threshold below which 15% of the voxels have lower densities and is used as the parameter for estimating the rate of lung density decline.

    Measured: Part B: Up to week 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2022
  2. Study start1 Jan 2024 (estimated)
  3. Primary completion26 Apr 2027 (estimated)
  4. Study completion7 May 2029 (estimated)

Why it stopped: Business decision

Resources

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
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05466747
Sponsor's protocol ID
TAK-883-4002
Other IDs
2022-502171-30-00
Status last verified
May 2023
First submitted
17 Jun 2022
Last updated
6 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing RYMPHYSIA and Another Available A1PI in people with Chronic Obstructive Pulmonary Disease (COPD) and Alpha1-Antitrypsin Deficiency, run by Takeda.

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 11 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 6 May 2023. 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?

Part A: Annual Rate of Change in the Physiologically Adjusted Lung Density (time frame: Up to Week 104). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05466747.

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 6 May 2023.

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