Phase 4, Double-blind Study Evaluating the Response on Computed Tomography (CT) Lung Density Decline Rates of Respreeza / Zemaira Weekly for 3 Years in Adults With alpha1 Antitrypsin Deficiency (AATD)

Phase 4Not Yet RecruitingNCT07326592

CSL Behring270 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

270

Conditions

Alpha1 Antitrypsin Deficiency Alpha1-Proteinase Inhibitor Deficiency Emphysema

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Annual rate of change in adjusted lung density

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).

Time frame: From Baseline to Month 36

Secondary Outcomes

Annual rate of change in forced expiratory volume in 1 second percent predicted (FEV1%)

The annual rate of change in FEV1% will be assessed by spirometry.

Time frame: From Baseline to Month 36

Annual rate of change in diffusion capacity of carbon monoxide (DLco)

The annual rate of change in DLco will be assessed by gas transfer using site machinery.

Time frame: From Baseline to Month 36

Number of severe pulmonary exacerbations

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.

Time frame: From screening up to Month 36

Duration of severe pulmonary exacerbations

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.

Time frame: From screening up to Month 36

Number of participants experiencing treatment emergent adverse events (TEAEs)

Time frame: From screening up to Month 36

Percentage of participants experiencing TEAEs

Time frame: From screening up to Month 36

Phase 4, Double-blind Study Evaluating the Response on Computed Tomography (CT) Lung Density Decline Rates of Respreeza / Zemaira Weekly for 3 Years in Adults With alpha1 Antitrypsin Deficiency (AATD)

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts