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)

A Phase 2/3, Multicenter, randOmized, Double-blind, Placebo-controlled, stUdy to evaLuate the Safety and Efficacy of Alpha-1 AntiTrypsin for the prEvention of Graft-versus-host Disease in Patients Receiving Hematopoietic Cell Transplant (MODULAATE Study)

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).

Study Overview

• Status: Completed
• Conditions: Acute-graft-versus-host Disease
• Intervention / Treatment: Biological: Placebo; Biological: AAT

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queenland
    • Herston, Queenland, Australia, 4029
      • Royal Brisbane and Women's Hospital
• Germany
  • Cologne, Germany, 50937
    • Uniklinik Köln
• Italy
  • Calabria, Italy, 89133
    • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
  • Catania
    • Calabria, Catania, Italy, 95123
      • University Hospital Catania
• Japan
  • Anjo-shi, Japan, 4668602
    • Anjo Kosei Hospital
  • Bunkyō City, Japan, 1138677
    • Tokyo Metropolitan Komagome Hospital
  • Hiroshima, Japan, 7348551
    • Hiroshima University Kasumi Campus
  • Nagoya, Japan, 4538511
    • Aichi Medical Center Nagoya Daiichi Hospital
  • Nagoya, Japan, 4668550
    • Nagoya University Hospital
  • Okayama, Japan, 71008558
    • Okayama University Hospital
  • Osaka, Japan, 5418567
    • Osaka International Cancer Institute
  • Osaka, Japan, 5458586
    • Osaka Metropolitan University Hospital
  • Sapporo, Japan, 0608648
    • Hokkaido University Hospital
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Busan, South Korea, 48108
    • Inje University Haeundae Paik Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Valle de Hebron
  • Barcelona, Spain, 39008
    • Marqués de Valdecilla university hospital
  • Salamanca, Spain, 37007
    • Salamanca University Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06200
    • Ankara Abdurrahman Yurtaslan
  • Battalgazi, Turkey (Türkiye), 44280
    • Turgut Ozal Medicine Center
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Scottsdale Shea Medical Center
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Johns Hopkins Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital Cleveland Medical Center
  • Texas
    • San Antonio, Texas, United States, 77030
      • The University of Texas-MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah Primary Children's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Albumin solution administered intravenously	Biological: Placebo; Albumin solution administered intravenously
Experimental: AAT (low dose); Open label. AAT is a lyophilized product for intravenous (IV) administration	Biological: AAT; AAT is a lyophilized product for IV administration.; Other Names: Alpha-1 proteinase inhibitor; Respreeza
Experimental: AAT (medium dose); Open label. AAT is a lyophilized product for IV administration	Biological: AAT; AAT is a lyophilized product for IV administration.; Other Names: Alpha-1 proteinase inhibitor; Respreeza
Experimental: AAT (high dose); Open label. AAT is a lyophilized product for IV administration	Biological: AAT; AAT is a lyophilized product for IV administration.; Other Names: Alpha-1 proteinase inhibitor; Respreeza
Experimental: AAT (selected dose from open-label); Double-blind. AAT is a lyophilized product for IV administration	Biological: AAT; AAT is a lyophilized product for IV administration.; Other Names: Alpha-1 proteinase inhibitor; Respreeza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of deaths (relapse and nonrelapse-related)	Death by any cause	Within 180, 365, and 730 days after HCT
Maximum concentration (Cmax) of AAT		Before and up to 72 after infusion of AAT
Area under the concentration curve (AUC) for AAT		Before and up to 72 after infusion of AAT
Clearance (CL) of AAT		Before and up to 72 after infusion of AAT
Volume of distribution (V) for AAT		Before and up to 72 after infusion of AAT
Ctrough of AAT		Before and up to 72 after infusion of AAT
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
Proportion of participants with Grade III-IV aGVHD or death		Through Days 60, 100, and 180 days after HCT
Proportion of participants with moderate to severe chronic GVHD	Moderate to severe chronic GVHD graded according to National Institutes of Health (NIH) scale.	Within 180, 365, 545, and 730 days after HCT
Proportion of participants who have discontinued immune suppression therapies including standard of care GVHD prophylaxis and steroid treatment		Within 180 and 365 days after HCT
Time to GVHD relapse-free survival	GVHD free, relapse free, survival defined as time to any of the following events: 1) Grade III-IV acute GVHD, 2) moderate-severe chronic GVHD, 3) primary malignancy relapse or 4) death.	Within 365 and 730 days after HCT
Proportion of participants with relapse of primary malignancies		Through 180, 365, and 730 days after HCT
Proportion of participants 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
Percent of participants with study drug related adverse events		Up to 365 days after HCT
Time to neutrophil engraftment	Time to the first of 3 consecutive days of absolute neutrophil counts ? 500/µL.	Through 365 days after HCT

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2019
• Primary Completion (Actual): March 19, 2026
• Study Completion (Actual): March 19, 2026

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Immune System Diseases; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Graft vs Host Disease; 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: CSL964_2001; 2018-000329-29 (EudraCT Number); 2024-511164-92-00 (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 (ie 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