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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)

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ClinicalTrials.gov Identifier: NCT03805789
Recruitment Status : Recruiting
First Posted : January 16, 2019
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Biological: Alpha-1 antitrypsin (AAT) Biological: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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)
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: Alpha-1 proteinase inhibitor

Placebo Comparator: Placebo
Albumin solution administered intravenously
Biological: Placebo
Albumin solution administered intravenously




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


Secondary Outcome Measures :
  1. Percent of subjects with Grade II-IV aGVHD or death (acute GVHD Free Survival) [ Time Frame: Through 100 days and 180 days post-hematopoietic cell transplant (HCT) ]
  2. Percent of subjects with Grade II-IV aGVHD [ Time Frame: Within 100 and 180 days post-HCT ]
  3. Percent of subjects with Grade III-IV acute GVHD [ Time Frame: Within 100 and 180 days post-HCT ]
  4. Percent of subjects with Grade II aGVHD [ Time Frame: Within 100 and 180 days post-HCT ]
  5. Percent of subjects with Grade III aGVHD [ Time Frame: Within 100 and 180 days post-HCT ]
  6. Percent of subjects with Grade IV aGVHD [ Time Frame: Within 100 and 180 days post-HCT ]
  7. Number of subjects with all-cause mortality [ Time Frame: Within 180 and 365 days post-HCT ]
    Death by any cause

  8. Time to all-cause mortality [ Time Frame: Up to 365 days post-HCT ]
    Time to death by any cause

  9. Time to non-relapse mortality [ Time Frame: Up to 365 days post-HCT ]
    Time to death by any cause other than relapse of primary malignancy

  10. Percent of subjects with moderate-to-severe chronic GVHD [ Time Frame: Within 180 and 365 days post-HCT ]
    Moderate-to-severe chronic GVHD graded according to NIH scale

  11. Percent of subjects with discontinuation of immune suppression therapies [ Time Frame: Within 180 and 365 days post-HCT ]
  12. Time to neutrophil engraftment [ Time Frame: Up to 365 days post-HCT ]
    Absolute neutrophil counts ≥ 500/µL

  13. Time to GVHD relapse-free survival [ Time Frame: Up to 365 days post-HCT ]
    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.

  14. Percent of subjects with relapse of primary malignancies [ Time Frame: Within 180 and 365 days post-HCT ]
  15. Percent of subjects with systemic infections [ Time Frame: At Days 60, 180, and 365 post-HCT ]
  16. Percent of subjects with study drug related adverse events [ Time Frame: Up to 365 days post-HCT ]
  17. Maximum concentration (Cmax) of AAT [ Time Frame: Before and up to 72 after infusion of AAT ]
  18. Area under the concentration curve (AUC) for AAT [ Time Frame: Before and up to 72 after infusion of AAT ]
  19. Clearance (CL) of AAT [ Time Frame: Before and up to 72 after infusion of AAT ]
  20. Volume of distribution (V) for AAT [ Time Frame: Before and up to 72 after infusion of AAT ]


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects, ≥12 years of age, 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
  • Planned umbilical cord blood (UCB) transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03805789


Contacts
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Contact: Trial Registration Coordinator 610-878-4000 clinicaltrials@cslbehring.com

Locations
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United States, Arizona
Scottsdale HH Cancer Transplant Recruiting
Scottsdale, Arizona, United States, 85258
Contact: use central contact         
United States, Tennessee
Centennial Medical Center Recruiting
Nashville, Tennessee, United States, 37203
Contact: use central contact         
Sponsors and Collaborators
CSL Behring

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT03805789     History of Changes
Other Study ID Numbers: CSL964_2001
2018-000329-29 ( EudraCT Number )
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action