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Completed

NCT Number: NCT03805789

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

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).

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Key information

Conditions

Acute-graft-versus-host Disease

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Royal Brisbane and Women's Hospital, Herston, Queenland, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

AAT

Biological

AAT is a lyophilized product for IV administration.

Other names: Alpha-1 proteinase inhibitor, Respreeza

Placebo

Biological

Albumin solution administered intravenously

Primary outcomes

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

    Time frame: Through 180 days after HCT

    Acute GVHD will be assessed using the Harris scoring system.

Secondary outcomes

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

    Time frame: 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

    Time frame: Through Day 60 after HCT

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

    Time frame: Through 100 days and 180 days after HCT

  4. Proportion of participants with lower GI aGVHD

    Time frame: Through Days 60, 100 and 180 after HCT

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

    Time frame: Through 100 and 180 days after HCT

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

    Time frame: Within 180, 365, and 730 days after HCT

    Death by any cause

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

    Time frame: Through Days 60, 100, and 180 days after HCT

  8. Proportion of participants with moderate to severe chronic GVHD

    Time frame: Within 180, 365, 545, and 730 days after HCT

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

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

    Time frame: Within 180 and 365 days after HCT

  10. Time to neutrophil engraftment

    Time frame: Through 365 days after HCT

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

  11. Time to GVHD relapse-free survival

    Time frame: Within 365 and 730 days after HCT

    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.

  12. Proportion of participants with relapse of primary malignancies

    Time frame: 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

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

  14. Percent of participants with study drug related adverse events

    Time frame: Up to 365 days after HCT

  15. Maximum concentration (Cmax) of AAT

    Time frame: Before and up to 72 after infusion of AAT

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

    Time frame: Before and up to 72 after infusion of AAT

  17. Ctrough of AAT

    Time frame: Before and up to 72 after infusion of AAT

  18. Clearance (CL) of AAT

    Time frame: Before and up to 72 after infusion of AAT

  19. Volume of distribution (V) for AAT

    Time frame: Before and up to 72 after infusion of AAT

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study 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)

Acronym: MODULAATE

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Jan 16, 2019
Registry last updated
Apr 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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