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Acute-graft-versus-host DiseasePhase 2/3MODULAATENCT03805789

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

A Phase 2/3 study testing AAT in people with Acute-graft-versus-host Disease, run by CSL Behring at 34 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Acute-graft-versus-host Disease
What is being tested?
AAT
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
222 participants
Where
34 sitesin 8 countries
Study dates
27 Mar 2019to 19 Mar 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • • 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.

Who cannot join

  • • 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 locations and contacts

34 sites in 8 countries.

34 sites in 8 countries

United States12 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Virginia Health System

    Charlottesville, Virginia, 22903

  • University Hospital Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • University of Utah Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • The University of Texas-MD Anderson Cancer Center

    San Antonio, Texas, 77030

  • HonorHealth Scottsdale Shea Medical Center

    Scottsdale, Arizona, 85258

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Johns Hopkins Hospital

    St. Petersburg, Florida, 33701

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

Japan9 sites

  • Anjo Kosei Hospital

    Anjo-shi, 4668602

  • Tokyo Metropolitan Komagome Hospital

    Bunkyō City, 1138677

  • Hiroshima University Kasumi Campus

    Hiroshima, 7348551

  • Aichi Medical Center Nagoya Daiichi Hospital

    Nagoya, 4538511

  • Nagoya University Hospital

    Nagoya, 4668550

  • Okayama University Hospital

    Okayama, 71008558

  • Osaka International Cancer Institute

    Osaka, 5418567

  • Osaka Metropolitan University Hospital

    Osaka, 5458586

  • Hokkaido University Hospital

    Sapporo, 0608648

Other trials in Japan

South Korea4 sites

  • INJE University Haeundae Paik Hospital

    Busan, 48108

  • Pusan National University Hospital

    Busan, 49241

  • Gachon University Gil Medical Center

    Incheon, 21565

  • Seoul National University Hospital

    Seoul, 03080

Other trials in South Korea

Spain3 sites

  • Hospital Universitario Valle de Hebron

    Barcelona, 08035

  • Marqués de Valdecilla University Hospital

    Barcelona, 39008

  • Salamanca University Hospital

    Salamanca, 37007

Other trials in Spain

Italy2 sites

  • University Hospital Catania

    Calabria, Catania, 95123

  • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

    Calabria, 89133

Other trials in Italy

Turkey (Türkiye)2 sites

  • Ankara Abdurrahman Yurtaslan

    Ankara, 06200

  • Turgut Ozal Medicine Center

    Battalgazi, 44280

Other trials in Turkey (Türkiye)

Australia1 site

  • Royal Brisbane and Women's Hospital

    Herston, Queenland, 4029

Other trials in Australia

Germany1 site

  • Uniklinik Köln

    Cologne, 50937

Other trials in Germany

About this study

Official 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)

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). This study consisted of two parts. In Part 1, the dose of Alpha1-Proteinase Inhibitor (AAT) to be used in Part 2 was identified based on safety and pharmacokinetic data. The selected dose was subsequently evaluated in Part 2, where the primary objective was to assess its efficacy in preventing aGVHD following HCT.

Being tested
AAT, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AATBiological

    Also called Alpha-1 proteinase inhibitor, Respreeza

    AAT is a lyophilized product for IV administration.

  • PlaceboBiological

    Albumin solution administered intravenously

Study groups in NCT03805789
Study groupRoleWhat they receive
AAT (low dose)ExperimentalOpen label. AAT is a lyophilized product for intravenous (IV) administration
Receives: Biological: AAT
AAT (medium dose)ExperimentalOpen label. AAT is a lyophilized product for IV administration
Receives: Biological: AAT
AAT (high dose)ExperimentalOpen label. AAT is a lyophilized product for IV administration
Receives: Biological: AAT
AAT (selected dose from open-label)ExperimentalDouble-blind. AAT is a lyophilized product for IV administration
Receives: Biological: AAT
PlaceboPlacebo comparatorAlbumin solution administered intravenously
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The time to Grade II-IV aGVHD or death

    Acute GVHD will be assessed using the Harris scoring system.

    Measured: Through 180 days after HCT

Secondary outcomes (19)

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

    Measured: Through 180 days after HCT

  2. 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

    Measured: Through Day 60 after HCT

  3. Proportion of participants with Grade II-IV aGVHD or death

    Measured: Through 100 days and 180 days after HCT

  4. Proportion of participants with lower GI aGVHD

    Measured: Through Days 60, 100 and 180 after HCT

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

    Measured: Through 100 and 180 days after HCT

  6. Number of deaths (relapse and nonrelapse-related)

    Death by any cause

    Measured: Within 180, 365, and 730 days after HCT

  7. Proportion of participants with Grade III-IV aGVHD or death

    Measured: Through Days 60, 100, and 180 days after HCT

  8. Proportion of participants with moderate to severe chronic GVHD

    Moderate to severe chronic GVHD graded according to National Institutes of Health (NIH) scale.

    Measured: Within 180, 365, 545, and 730 days after HCT

  9. Proportion of participants who have discontinued immune suppression therapies including standard of care GVHD prophylaxis and steroid treatment

    Measured: Within 180 and 365 days after HCT

  10. Time to neutrophil engraftment

    Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL.

    Measured: Through 365 days after HCT

  11. 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.

    Measured: Within 365 and 730 days after HCT

  12. Proportion of participants with relapse of primary malignancies

    Measured: Through 180, 365, and 730 days after HCT

  13. Proportion of participants with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response

    Measured: Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period

  14. Percent of participants with study drug related adverse events

    Measured: Up to 365 days after HCT

  15. Maximum concentration (Cmax) of AAT

    Measured: Before and up to 72 after infusion of AAT

  16. Area under the concentration curve (AUC) for AAT

    Measured: Before and up to 72 after infusion of AAT

  17. Ctrough of AAT

    Measured: Before and up to 72 after infusion of AAT

  18. Clearance (CL) of AAT

    Measured: Before and up to 72 after infusion of AAT

  19. Volume of distribution (V) for AAT

    Measured: Before and up to 72 after infusion of AAT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2019
  2. Study start27 Mar 2019
  3. Primary completion19 Mar 2026
  4. Study completion19 Mar 2026

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
222 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03805789
Sponsor's protocol ID
CSL964_2001
Other IDs
2018-000329-29, 2024-511164-92-00, 2018
Acronym
MODULAATE
Status last verified
Aug 2026
First submitted
14 Jan 2019
Last updated
9 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing AAT in people with Acute-graft-versus-host Disease, run by CSL Behring at 34 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Japan, South Korea, Spain, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The time to Grade II-IV aGVHD or death (time frame: Through 180 days after HCT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03805789.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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