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)

A Phase 4, Multicenter, Double-blind, Study to Investigate the Efficacy, Safety, and Tolerability of 3 Active Doses of Respreeza® / Zemaira® Weekly Intravenous Infusions Administered Over 3 Years as Longterm Maintenance Therapy in Adult Subjects With Emphysema Related to Alpha1 Antitrypsin Deficiency

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 Overview

• Status: Not yet recruiting
• Conditions: Emphysema; Alpha1 Antitrypsin Deficiency; Alpha1-Proteinase Inhibitor Deficiency
• Intervention / Treatment: Biological: CE1226

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: +1 610-878-4697; Email: clinicaltrials@cslbehring.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CE1226 low dose; CE1226 at low dose.	Biological: CE1226; CE1226 will be administered via intravenous (IV) infusion weekly over 3 years.; Other Names: Zemaira; Respreeza; Human alpha1-proteinase inhibitor
Experimental: CE1226 medium dose; CE1226 at medium dose.	Biological: CE1226; CE1226 will be administered via intravenous (IV) infusion weekly over 3 years.; Other Names: Zemaira; Respreeza; Human alpha1-proteinase inhibitor
Experimental: CE1226 high dose; CE1226 at high dose.	Biological: CE1226; CE1226 will be administered via intravenous (IV) infusion weekly over 3 years.; Other Names: Zemaira; Respreeza; Human alpha1-proteinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From Baseline to Month 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	From screening up to Month 36
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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2026
• Primary Completion (Estimated): September 15, 2033
• Study Completion (Estimated): September 15, 2033

Study Registration Dates

• First Submitted: January 7, 2026
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Pulmonary Disease; Progressive Emphysema
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Emphysema; alpha 1-Antitrypsin Deficiency; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Blood Proteins; Serum Globulins; Globulins; Glycoproteins; Glycoconjugates; Acute-Phase Proteins; Serpins; Alpha-Globulins; alpha 1-Antitrypsin; Respreeza
• Other Study ID Numbers: CE1226_4003; 2025-522964-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (i.e. FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No