Register a trial

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03805789




Registration number
NCT03805789
Ethics application status
Date submitted
14/01/2019
Date registered
16/01/2019

Titles & IDs
Public title
The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-Versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant
Scientific title
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)
Secondary ID [1] 0 0
2018-000329-29
Secondary ID [2] 0 0
CSL964_2001
Universal Trial Number (UTN)
Trial acronym
MODULAATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute-graft-versus-host Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Alpha-1 antitrypsin (AAT)
Treatment: Other - Placebo

Experimental: AAT (low dose) - Open label. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration

Experimental: AAT (medium dose) - Open label. AAT is a lyophilized product for intravenous administration

Experimental: AAT (high dose) - Open label. AAT is a lyophilized product for intravenous administration

Experimental: AAT (selected dose from open-label) - Double-blind. AAT is a lyophilized product for intravenous administration

Placebo comparator: Placebo - Albumin solution administered intravenously


Treatment: Other: Alpha-1 antitrypsin (AAT)
Alpha-1 antitrypsin is a lyophilized product for intravenous administration.

Treatment: Other: Placebo
Albumin solution administered intravenously
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The time to Grade II-IV acute graft versus host disease (aGVHD) or death
Timepoint [1] 0 0
Through 180 days after hematopoietic cell transplantation (HCT)
Secondary outcome [1] 0 0
Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ
Timepoint [1] 0 0
Through 180 days after HCT
Secondary outcome [2] 0 0
Proportion of subjects with severe infections defined by NCI-CTCAE = Grade 3
Timepoint [2] 0 0
Through Day 60 after HCT
Secondary outcome [3] 0 0
Proportion of subjects with Grade II-IV aGVHD or death
Timepoint [3] 0 0
Through 100 days and 180 days after HCT
Secondary outcome [4] 0 0
Proportion of subjects with lower GI aGVHD
Timepoint [4] 0 0
Through Days 60, 100 and 180 after HCT
Secondary outcome [5] 0 0
Proportion of subjects with severe infections defined by NCI-CTCAE = Grade 3
Timepoint [5] 0 0
Through 100 and 180 days after HCT
Secondary outcome [6] 0 0
Number of deaths (relapse and nonrelapse-related)
Timepoint [6] 0 0
Within 180, 365, and 730 days after HCT
Secondary outcome [7] 0 0
Proportion of subjects with Grade III-IV aGVHD or death
Timepoint [7] 0 0
Through Days 60, 100, and 180 days after HCT
Secondary outcome [8] 0 0
Proportion of subjects with moderate-to-severe chronic GVHD
Timepoint [8] 0 0
Within 180, 365, 545, and 730 days after HCT
Secondary outcome [9] 0 0
Proportion of subjects who have discontinued immune suppression therapies including standard- of- care GVHD prophylaxis and steroid treatment
Timepoint [9] 0 0
Within 180 and 365 days after HCT
Secondary outcome [10] 0 0
Time to neutrophil engraftment
Timepoint [10] 0 0
Through 365 days after HCT
Secondary outcome [11] 0 0
Time to GVHD relapse-free survival
Timepoint [11] 0 0
Within 365 and 730 days after HCT
Secondary outcome [12] 0 0
Proportion of subjects with relapse of primary malignancies
Timepoint [12] 0 0
Through 180, 365, and 730 days after HCT
Secondary outcome [13] 0 0
Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response
Timepoint [13] 0 0
Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
Secondary outcome [14] 0 0
Percent of subjects with study drug related adverse events
Timepoint [14] 0 0
Up to 365 days after HCT
Secondary outcome [15] 0 0
Maximum concentration (Cmax) of AAT
Timepoint [15] 0 0
Before and up to 72 after infusion of AAT
Secondary outcome [16] 0 0
Area under the concentration curve (AUC) for AAT
Timepoint [16] 0 0
Before and up to 72 after infusion of AAT
Secondary outcome [17] 0 0
Clearance (CL) of AAT
Timepoint [17] 0 0
Before and up to 72 after infusion of AAT
Secondary outcome [18] 0 0
Volume of distribution (V) for AAT
Timepoint [18] 0 0
Before and up to 72 after infusion of AAT
Secondary outcome [19] 0 0
Ctrough of AAT
Timepoint [19] 0 0
Before and up to 72 after infusion of AAT

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2027
Actual
Sample size
Target
310
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Queenlan
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Germany
State/province [13] 0 0
Köln
Country [14] 0 0
Italy
State/province [14] 0 0
Catania
Country [15] 0 0
Italy
State/province [15] 0 0
Calabria
Country [16] 0 0
Japan
State/province [16] 0 0
Anjo-shi
Country [17] 0 0
Japan
State/province [17] 0 0
Bunkyo-ku
Country [18] 0 0
Japan
State/province [18] 0 0
Hiroshima
Country [19] 0 0
Japan
State/province [19] 0 0
Nagoya-shi
Country [20] 0 0
Japan
State/province [20] 0 0
Nagoya
Country [21] 0 0
Japan
State/province [21] 0 0
Okayama-shi
Country [22] 0 0
Japan
State/province [22] 0 0
Osaka-shi
Country [23] 0 0
Japan
State/province [23] 0 0
Sapporo
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Busan
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Incheon
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Salamanca
Country [29] 0 0
Turkey
State/province [29] 0 0
Ankara
Country [30] 0 0
Turkey
State/province [30] 0 0
Battalgazi

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Physician
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Registration Coordinator
Address 0 0
Country 0 0
Phone 0 0
610-878-4000
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03805789