The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (MODULAATE)

CSL Behring

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Acute-graft-versus-host Disease

Treatments: Biological: AAT; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03805789

2024-511164-92-00 (EU Trial (CTIS) Number)

2018-000329-29 (EudraCT Number)

CSL964_2001

Details and patient eligibility

About

This study is a phase 2 / 3 prospective, double-blind, randomized, multicenter, placebo-controlled study for prevention of acute GVHD (aGVHD) in participants undergoing an unrelated (matched or single allele mismatched) or matched related allogeneic hematopoietic cell transplantation (HCT).

Enrollment: 310 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participants, >=12 years of age (>= 18 years of age for participants at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome, and myeloproliferative neoplasms.

• Planned myeloablative conditioning regimen.

• 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

• Prior autologous or allogeneic HCT.
• 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.
• Planned umbilical cord blood transplant.
• Planned use of cyclophosphamide after HCT for GVHD prophylaxis.
• Planned haploidentical donor.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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310 participants in 5 patient groups, including a placebo group

AAT (low dose)

Experimental group

Description:

Open label. AAT is a lyophilized product for intravenous (IV) administration

Treatment:

Biological: AAT

AAT (medium dose)

Experimental group

Description:

Open label. AAT is a lyophilized product for IV administration

Treatment:

Biological: AAT

AAT (high dose)

Experimental group

Description:

Open label. AAT is a lyophilized product for IV administration

Treatment:

Biological: AAT

AAT (selected dose from open-label)

Experimental group

Description:

Double-blind. AAT is a lyophilized product for IV administration

Treatment:

Biological: AAT

Placebo

Placebo Comparator group

Description:

Albumin solution administered intravenously

Treatment:

Biological: Placebo