Alpha1 Antitrypsin Deficiency, Alpha1-Proteinase Inhibitor Deficiency, Emphysema
Conditions
Keywords
Progressive Emphysema, Chronic Pulmonary Disease
Brief summary
This is a multicenter, parallel-group, double-blind, randomized phase 4 study designed to identify the optimal dose of CE1226 (2 active doses) to slow disease progression as assessed by reduced rates of annual lung density decline in alpha-1 antitrypsin (AAT) deficient participants over 3 years as compared with the marketed dose 60 milligrams per kilogram (mg/kg).
Interventions
BIOLOGICALCE1226
CE1226 will be administered via intravenous (IV) infusion weekly over 3 years.
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor will also be blinded to treatment allocation.
Intervention model description
This is a double blind, parallel group assignment study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* • Age greater than or equal to (\>=) 18 and less than or equal to (\<=) 65 years at the time of providing written informed consent. * • Confirmed diagnosis of emphysema related to AATD with either the PiZZ, PiZ(null), or Pi(null/null) genotype with documented serum AAT levels less than (\<) 11 micrometer (μM) (or \< 50 mg/dL \[milligram/deciliter\]) at any time before the first administration of CE1226 on Day 1 (Baseline).
Exclusion criteria
* • Participants should not have acute illness or pulmonary exacerbation within 6 weeks before the first administration of CE1226 on Day 1 (Baseline). * • Participants should not have previously received gene therapy for AATD at any point. * • Participants with liver disease secondary to AATD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual rate of change in adjusted lung density | From Baseline to Month 36 | The annual rate of change (expressed as gram per liter per year \[g/L/year\]) in adjusted lung density (15th percentile lung density \[PD15\]) will be calculated on CT scan assessments of whole lung at total lung capacity (TLC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annual rate of change in forced expiratory volume in 1 second percent predicted (FEV1%) | From Baseline to Month 36 | The annual rate of change in FEV1% will be assessed by spirometry. |
| Annual rate of change in diffusion capacity of carbon monoxide (DLco) | From Baseline to Month 36 | The annual rate of change in DLco will be assessed by gas transfer using site machinery. |
| Number of severe pulmonary exacerbations | From screening up to Month 36 | Pulmonary excerbations will be assessed by the investigator using Rodriguez-Roisin criteria, where an exacerbation is defined as: a sustained worsening of the patient's condition, from a stable state and beyond normal day-to-day variations, necessitating a change in regular medication in a patient with underlying chronic obstructive pulmonary disease (COPD). A severe exacerbation is defined as an event requiring the introduction of corticosteroids and / or antibiotics which results in hospitalization or death. |
| Duration of severe pulmonary exacerbations | From screening up to Month 36 | Pulmonary excerbations will be assessed by the investigator using Rodriguez-Roisin criteria, where an exacerbation is defined as: a sustained worsening of the patient's condition, from a stable state and beyond normal day-to-day variations, necessitating a change in regular medication in a patient with underlying COPD. A severe exacerbation is defined as an event requiring the introduction of corticosteroids and / or antibiotics which results in hospitalization or death. |
| Number of participants experiencing treatment emergent adverse events (TEAEs) | From screening up to Month 36 | — |
| Percentage of participants experiencing TEAEs | From screening up to Month 36 | — |
Contacts
CONTACTTrial Registration Coordinator
STUDY_DIRECTORStudy Director
CSL Behring
Outcome results
None listed