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, multi-center, placebo-controlled study for prevention of acute GVHD (aGVHD) in subjects undergoing an allogeneic hematopoietic cell transplant (HCT).

Study Overview

• Status: Recruiting
• Conditions: Acute-graft-versus-host Disease
• Intervention / Treatment: Biological: Alpha-1 antitrypsin (AAT); Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 310
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: 610-878-4000; Email: clinicaltrials@cslbehring.com

Study Locations

• Australia
  • Queenland
    • Herston, Queenland, Australia, 4029
      • Recruiting
      • Royal Brisbane and Women's Hospital
      • Contact: Use Central Contact
• Germany
  • Köln, Germany, 50937
    • Recruiting
    • Uniklinik Köln, lnnere Mediz
    • Contact: Use Central Contact
• Italy
  • Calabria, Italy, 89133
    • Recruiting
    • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
    • Contact: Use Central Contact
  • Catania
    • Calabria, Catania, Italy, 95123
      • Recruiting
      • University Hospital Catania
      • Contact: Use Central Contact
• Japan
  • Anjo-shi, Japan, 4668602
    • Active, not recruiting
    • Anjo Kosei Hospital
  • Bunkyo-ku, Japan, 1138677
    • Active, not recruiting
    • Tokyo Metropolitan Komagome Hospital
  • Hiroshima, Japan, 7348551
    • Active, not recruiting
    • Hiroshima University Kasumi Campus
  • Nagoya, Japan, 4668550
    • Active, not recruiting
    • Nagoya University Hospital
  • Nagoya-shi, Japan, 4538511
    • Active, not recruiting
    • Aichi Medical Center Nagoya Daiichi Hospital
  • Okayama-shi, Japan, 71008558
    • Active, not recruiting
    • Okayama University Hospital
  • Osaka-shi, Japan, 5418567
    • Active, not recruiting
    • Osaka International Cancer Institute
  • Osaka-shi, Japan, 5458586
    • Active, not recruiting
    • Osaka Metropolitan University Hospital
  • Sapporo, Japan, 0608648
    • Active, not recruiting
    • Hokkaido University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Recruiting
    • Pusan National University Hospital
    • Contact: Use Central Contact
  • Busan, Korea, Republic of, 48108
    • Recruiting
    • Inje University Haeundae Paik Hospital
    • Contact: Use Central Contact
  • Incheon, Korea, Republic of, 21565
    • Recruiting
    • Gachon University Gil Medical Center
    • Contact: Use Central Contact
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Use Central Contact
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Valle de Hebrón
    • Contact: Use Central Contact
  • Barcelona, Spain, 39008
    • Recruiting
    • Marqués de Valdecilla University Hospital
    • Contact: Use Central Contact
  • Salamanca, Spain, 37007
    • Recruiting
    • Salamanca University Hospital
    • Contact: Use Central Contact
• Turkey
  • Ankara, Turkey, 06200
    • Recruiting
    • Ankara Abdurrahman Yurtaslan
    • Contact: Use Central Contact
  • Battalgazi, Turkey, 44280
    • Recruiting
    • Turgut Ozal Medicine Center
    • Contact: Use Central Contact
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • HonorHealth Scottsdale Shea Medical Center
      • Contact: Use Central Contact
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Use Central Contact
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Use Central Contact
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Cancer Center
      • Contact: Use Central Contact
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Use Central Contact
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Medical Center
      • Contact: Use Central Contact
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
      • Contact: Use Central Contact
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospital Cleveland Medical Center
      • Contact: Use Central Contact
  • Texas
    • San Antonio, Texas, United States, 77030
      • Recruiting
      • The University of Texas-MD Anderson Cancer Center
      • Contact: Use Central Contact
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Active, not recruiting
      • University of Utah Primary Children's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Health System
      • Contact: Use Central Contact
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center
      • Contact: Use Central Contact

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Planned myeloablative conditioning regimen

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 (UCB) transplant

Study Plan

How is the study designed?

Design Details

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

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. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration	Biological: Alpha-1 antitrypsin (AAT); Alpha-1 antitrypsin is a lyophilized product for intravenous administration.; Other Names: Alpha-1 proteinase inhibitor
Experimental: AAT (medium dose); Open label. AAT is a lyophilized product for intravenous administration	Biological: Alpha-1 antitrypsin (AAT); Alpha-1 antitrypsin is a lyophilized product for intravenous administration.; Other Names: Alpha-1 proteinase inhibitor
Experimental: AAT (high dose); Open label. AAT is a lyophilized product for intravenous administration	Biological: Alpha-1 antitrypsin (AAT); Alpha-1 antitrypsin is a lyophilized product for intravenous administration.; Other Names: Alpha-1 proteinase inhibitor
Experimental: AAT (selected dose from open-label); Double-blind. AAT is a lyophilized product for intravenous administration	Biological: Alpha-1 antitrypsin (AAT); Alpha-1 antitrypsin is a lyophilized product for intravenous administration.; Other Names: Alpha-1 proteinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to Grade II-IV acute graft versus host disease (aGVHD) or death	Acute graft vs host disease (aGVHD) will be assessed using the modified Keystone GVHD scoring system.	Through 180 days after hematopoietic cell transplantation (HCT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ		Through 180 days after HCT
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3		Through Day 60 after HCT
Proportion of subjects with Grade II-IV aGVHD or death		Through 100 days and 180 days after HCT
Proportion of subjects with lower GI aGVHD		Through Days 60, 100 and 180 after HCT
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3		Through 100 and 180 days after HCT
Number of deaths (relapse and nonrelapse-related)	Death by any cause	Within 180, 365, and 730 days after HCT
Proportion of subjects with Grade III-IV aGVHD or death		Through Days 60, 100, and 180 days after HCT
Proportion of subjects with moderate-to-severe chronic GVHD	Moderate-to-severe chronic GVHD graded according to NIH scale	Within 180, 365, 545, and 730 days after HCT
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
Time to neutrophil engraftment	Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL	Through 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 II-IV acute GVHD, 2) moderate-severe chronic GVHD, 3) primary malignancy relapse or 4) death.	Within 365 and 730 days after HCT
Proportion of subjects with relapse of primary malignancies		Through 180, 365, and 730 days after HCT
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
Percent of subjects with study drug related adverse events		Up to 365 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

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 (Estimated): September 1, 2025
• Study Completion (Estimated): March 1, 2027

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): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Protease Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor
• Other Study ID Numbers: CSL964_2001; 2018-000329-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No