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)

2025-522964-33-00 Protocol CE1226_4003 Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 2 sites · Protocol CE1226_4003

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 33
Countries 1
Sites 2

Alpha1-proteinase inhibitor deficiency

This is a study to primarily assess the ability of the 2 active doses of CE1226 (Respreeza / Zemaira) to influence the annual lung density decline rate as compared to the marketed dose of CE1226 in participants with AATD.

Key facts

Sponsor
CSL Behring LLC
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Respiratory Tract Diseases [C08]
Decision date (initial)
2026-05-28
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
CSL Behrung LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

This is a study to primarily assess the ability of the 2 active doses of CE1226 (Respreeza / Zemaira) to influence the annual lung density decline rate as compared to the marketed dose of CE1226 in participants with AATD.

Conditions and MedDRA coding

Alpha1-proteinase inhibitor deficiency

VersionLevelCodeTermSystem organ class
28.0 LLT 10001806 Alpha-1 anti-trypsin deficiency 10010331
20.0 SOC 10010331 Congenital familial and genetic disorders 21

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Overall study
This is a double blind parallel group assignment study.
 Randomised Controlled Double [{"id":173378,"code":3,"name":"Monitor"},{"id":173381,"code":4,"name":"Analyst"},{"id":173379,"code":1,"name":"Subject"},{"id":173380,"code":2,"name":"Investigator"},{"id":173377,"code":5,"name":"Carer"}] CE1226 low dose: CE1226 at low dose.
CE1226 medium dose: CE1226 at medium dose.
CE1226 high dose: CE1226 at high dose.

Regulatory references

Scientific advice from competent authorities
European Medicines Agency, Food And Drug Administration
Plan to share 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 [email protected].

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. • 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 1

  1. • 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Annual rate of change in adjusted lung density

Secondary endpoints 1

  1. 1. Annual rate of change in forced expiratory volume in 1 second percent predicted (FEV1%) 2. Annual rate of change in diffusion capacity of carbon monoxide (DLco) 3. Number of severe pulmonary exacerbations 4. Duration of severe pulmonary exacerbations 5. Number of participants experiencing treatment emergent adverse events (TEAEs) 6. Percentage of participants experiencing TEAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Respreeza 4,000 mg powder and solvent for solution for infusion.

PRD6696134 · Product

Active substance
Human ALPHA1-PROTEINASE Inhibitor
Substance synonyms
Human alfa-1-proteinase inhibitor, ALPHA-1-ANTITRYPSIN, ALPHA-1-PROTEINASE INHIBITOR (HUMAN), ALPHA-1-PROTEASE INHIBITOR
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
00 mg/kg milligram(s)/kilogram
Max total dose
00 mg/kg milligram(s)/kilogram
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
B02AB02 — ALFA1 ANTITRYPSIN
Marketing authorisation
EU/1/15/1006/002
MA holder
CSL BEHRING GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Differences are included in sIMPD-Q, available in the Section G.

Respreeza 1,000 mg powder and solvent for solution for infusion.

PRD3193174 · Product

Active substance
Human ALPHA1-PROTEINASE Inhibitor
Substance synonyms
Human alfa-1-proteinase inhibitor, ALPHA-1-ANTITRYPSIN, ALPHA-1-PROTEINASE INHIBITOR (HUMAN), ALPHA-1-PROTEASE INHIBITOR
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
00 mg/Kg milligram(s)/kilogram
Max total dose
00 mg/Kg milligram(s)/kilogram
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
B02AB02 — ALFA1 ANTITRYPSIN
Marketing authorisation
EU/1/15/1006/001
MA holder
CSL BEHRING GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Differences are included in sIMPD-Q, available in the Section G.

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CSL Behring LLC

17 Total trials 3 Recruiting 10 Ended
Commercial
Sponsor organisation
CSL Behring LLC
Address
1020 1st Avenue
City
King Of Prussia
Postcode
19406-1310
Country
United States

Scientific contact point

Organisation
CSL Behring LLC
Contact name
Study Director

Public contact point

Organisation
CSL Behring LLC
Contact name
Trial Registration Coordinator

Third parties 4

OrganisationCity, countryDuties
PPD Development LP
ORG-100011560
 Wilmington, United States On site monitoring, Code 10, Code 12, Code 2, Interactive response technologies (IRT), Laboratory analysis, Code 5, Data management, E-data capture, Code 8, Code 9
Imc University Of Applied Sciences Krems
ORG-100023870
 Krems, Austria Other
Pharmaceutical Product Development LLC
ORG-100016999
 Richmond, United States Other
Suvoda LLC
ORG-100043523
 Conshohocken, United States Interactive response technologies (IRT)

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Authorised, recruitment pending 33 2
Rest of world — 0 —

Investigational sites

Denmark

2 sites · Authorised, recruitment pending
Sygehus Lillebaelt Vejle Sygehus
Department of Medicine, Beriderbakken 4, 7100, Vejle
Aalborg University Hospital
Department of Respitatory Diseases, Moelleparkvej 4, 9000, Aalborg

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_CSL Behring_CE1226_4003_Protocol_2025-522964-33-00_Public 1.0
Protocol (for publication) D4_CSL Behring_CE1226_4003_ Daily Diary_DNK_ENG_Public 1.0
Protocol (for publication) D4_CSL Behring_CE1226_4003_Modified MRC Dyspnea_Scale_DNK_ENG_Public 2.0
Protocol (for publication) D4_CSL Behring_CE1226_4003_Questionnaires Placeholder_Public n/a
Recruitment arrangements (for publication) K1_CE1226_4003_Recruitment_Arrangement_Informed_Consent_Procedure_DNK_Public n/a
Subject information and informed consent form (for publication) L1_CE1226_4003_Main_ICF_DNK_DA_Public 2.0
Subject information and informed consent form (for publication) L1_CE1226_4003_Right-not-to-Know_ICF_DNK_DA_Public 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_CSL Behring_CE1226_4003_SMPC_Respreeza n/a
Synopsis of the protocol (for publication) D1_CSL Behring_CE1226_4003_Lay Protocol Synopsis_2025-522964-33-00_ENG_Public 1.0

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-12-18 Denmark Acceptable
2026-03-09
 2026-05-28