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

NCT03805789 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: CSL964_20012018-000329-292024-511164-92-00
• Study Type: interventional
• Target: 222
• Locations: 8 countries
• Sites: 34

Brief Summary

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).

Conditions

Acute-graft-versus-host Disease

Outcome Measures

Primary Outcomes (1)

• The time to Grade II-IV aGVHD or death

  Acute GVHD will be assessed using the Harris scoring system.

  Through 180 days after HCT

Secondary Outcomes (19)

• Proportion of participants with lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ

  Through 180 days after HCT

• Proportion of participants with severe infections defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) greater than or equal to (>=) Grade 3

  Through Day 60 after HCT

• Proportion of participants with Grade II-IV aGVHD or death

  Through 100 days and 180 days after HCT

• Proportion of participants with lower GI aGVHD

  Through Days 60, 100 and 180 after HCT

• Proportion of participants with severe infections defined by NCI-CTCAE >= Grade 3

  Through 100 and 180 days after HCT

Study Arms (5)

AAT (low dose)

EXPERIMENTAL

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

Biological: AAT

AAT (medium dose)

EXPERIMENTAL

Open label. AAT is a lyophilized product for IV administration

Biological: AAT

AAT (high dose)

EXPERIMENTAL

Open label. AAT is a lyophilized product for IV administration

Biological: AAT

AAT (selected dose from open-label)

EXPERIMENTAL

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

Biological: AAT

Placebo

PLACEBO COMPARATOR

Albumin solution administered intravenously

Biological: Placebo

Interventions

AAT BIOLOGICAL

AAT is a lyophilized product for IV administration.

Also known as: Alpha-1 proteinase inhibitor, Respreeza

AAT (high dose); AAT (low dose); AAT (medium dose); AAT (selected dose from open-label)

Placebo BIOLOGICAL

Albumin solution administered intravenously

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (34)

HonorHealth Scottsdale Shea Medical Center

Scottsdale, Arizona, 85258, United States

Location

Johns Hopkins Hospital

St. Petersburg, Florida, 33701, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The University of Texas-MD Anderson Cancer Center

San Antonio, Texas, 77030, United States

Location

University of Utah Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Royal Brisbane and Women's Hospital

Herston, Queenland, 4029, Australia

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

University Hospital Catania

Calabria, Catania, 95123, Italy

Location

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

Calabria, 89133, Italy

Location

Anjo Kosei Hospital

Anjo-shi, 4668602, Japan

Location

Tokyo Metropolitan Komagome Hospital

Bunkyō City, 1138677, Japan

Location

Hiroshima University Kasumi Campus

Hiroshima, 7348551, Japan

Location

Aichi Medical Center Nagoya Daiichi Hospital

Nagoya, 4538511, Japan

Location

Nagoya University Hospital

Nagoya, 4668550, Japan

Location

Okayama University Hospital

Okayama, 71008558, Japan

Location

Osaka International Cancer Institute

Osaka, 5418567, Japan

Location

Osaka Metropolitan University Hospital

Osaka, 5458586, Japan

Location

Hokkaido University Hospital

Sapporo, 0608648, Japan

Location

INJE University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitario Valle de Hebron

Barcelona, 08035, Spain

Location

Marqués de Valdecilla University Hospital

Barcelona, 39008, Spain

Location

Salamanca University Hospital

Salamanca, 37007, Spain

Location

Ankara Abdurrahman Yurtaslan

Ankara, 06200, Turkey (Türkiye)

Location

Turgut Ozal Medicine Center

Battalgazi, 44280, Turkey (Türkiye)

Location

MeSH Terms

Interventions

alpha 1-Antitrypsin; Respreeza

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Officials

• Study Physician

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 16, 2019
• Study Start: March 27, 2019
• Primary Completion: March 19, 2026
• Study Completion: March 19, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.
• 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.

Locations

DE (1); ES (3); KR (4); TU (2); JP (9); IT (2); US (12); AU (1)