The safety and efficacy of Alpha-1 Antitrypsin (AAT) for the prevention of graft‑versus-host disease (GVHD) in patients receiving hematopoietic cell transplant.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CSL Behring LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

17 May 2019 → 19 Mar 2026

Decision date (initial)

2024-05-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

CSL Behring LLC

External identifiers

EU CT number

2024-511164-92-00

EudraCT number

2018-000329-29

ClinicalTrials.gov

NCT03805789

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Pharmacokinetic, Prophylaxis, Pharmacodynamic

Primary objective is to evaluate the efficacy of AAT at the selected dose for the prevention of acute GVHD following HCT.

Secondary objectives 1

1. Key Secondary Objective is To evaluate the efficacy of AAT for the prevention of severe aGVHD and infections following HCT. Also, 1. To further evaluate the efficacy of AAT for the prevention of complications after HCT. 2. To evaluate the safety of AAT based on investigational product- (IP)- related AEs. 3. To evaluate the steady state PK of AAT in HCT recipients.

Conditions and MedDRA coding

Acute Graft versus host disease

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Pharmaceuticals And Medical Devices 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 3

1. Male or female subjects, ≥12 years of age (≥ 18 years of age for subjects at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma multiple myeloma, myelodysplastic syndrome and myeloproliferative neoplasms.
2. Planned myeloablative conditioning regimen.
3. Participants must have a related or unrelated donor as follows: - Related donor must be a 6 / 6 match for human leukocyte antigen (HLA)-A, -B, at intermediate (or higher) resolution, and -DR beta 1 (DRB1) at high resolution using deoxyribonucleic acid (DNA)-based typing. - Unrelated donor must be 7 / 8 or 8 / 8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing.

Exclusion criteria 5

1. Prior autologous or allogeneic HCT.
2. T-cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo (ie, anti‑thymocyte globulin [ATG], alemtuzumab) for GVHD prophylaxis.
3. Planned umbilical cord blood transplant.
4. Planned use of cyclophosphamide after HCT for GVHD prophylaxis.
5. Planned haploidentical donor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The time to Grade II-IV aGVHD or death through 180 days after hematopoietic cell transplantation (HCT).

Secondary endpoints 19

1. Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ. Through 180 days after HCT.
2. Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3. Through Day 60 after HCT.
3. Proportion of subjects with Grade II-IV aGVHD or death. Through 100 and 180 days after HCT.
4. Proportion of subjects with lower GI aGVHD. Through Days 60, 100 and 180 after HCT.
5. Deaths (relapse and nonrelapse-related). Within 180, 365, and 730 days after HCT.
6. Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3. Through 100 and 180 days after HCT.
7. Proportion of subjects with Grade III-IV aGVHD or death. Through Days 60, 100, and 180 days after HCT.
8. Proportion of subjects with moderate-to-severe chronic GVHD. Within 180, 365, 545, and 730 days after HCT.
9. Proportion of subjects who have discontinued immune suppression therapies including standard-of-care GVHD prophylaxis and steroid treatment. Within 180 and 365 days after HCT.
10. Time to neutrophil engraftment. Through 365 days after HCT.
11. Time to GVHD relapse-free survival. Within 365 and 730 days after HCT.
12. Proportion of subjects with relapse of primary malignancies. Through 180, 365, and 730 days after HCT.
13. Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response. Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
14. Percent of subjects with study drug-related adverse events. Up to 365 days after HCT.
15. Maximum concentration (Cmax) of AAT. Before and up to 72 after infusion of AAT.
16. Area under the concentration curve for AAT. Before and up to 72 after infusion of AAT.
17. Clearance of AAT. Before and up to 72 after infusion of AAT.
18. Volume of distribution for AAT. Before and up to 72 after infusion of AAT.
19. Ctrough of AAT. Before and up to 72 after infusion of AAT.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CSL Behring LLC

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

Study Director

Third parties 12

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 49 files

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

Application history

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