Clinical Trials/NCT03805789

NCT03805789

Completed

Phase 2

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)

CSL Behring68 sites in 8 countries222 target enrollmentMarch 27, 2019

ConditionsAcute-graft-versus-host Disease

InterventionsAAT Placebo

DrugsAAT Placebo

Overview

Phase: Phase 2
Intervention: AAT
Conditions: Acute-graft-versus-host Disease
Sponsor: CSL Behring
Enrollment: 222
Locations: 68
Primary Endpoint: The time to Grade II-IV aGVHD or death
Status: Completed
Last Updated: 10 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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).

Registry

clinicaltrials.gov

Start Date

March 27, 2019

End Date

March 19, 2026

Last Updated

10 days ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

CSL Behring

Responsible Party

Sponsor

Eligibility Criteria

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.

Arms & Interventions

AAT (low dose)

Open label. AAT is a lyophilized product for intravenous (IV) administration

Intervention: AAT

AAT (high dose)

Open label. AAT is a lyophilized product for IV administration

Intervention: AAT

Placebo

Albumin solution administered intravenously

Intervention: Placebo

AAT (selected dose from open-label)

Double-blind. AAT is a lyophilized product for IV administration

Intervention: AAT

AAT (medium dose)

Open label. AAT is a lyophilized product for IV administration

Intervention: AAT

Outcomes

Primary Outcomes

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

Proportion of participants with lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ(Through 180 days after HCT)
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(Through Day 60 after HCT)
Proportion of participants with Grade II-IV aGVHD or death(Through 100 days and 180 days after HCT)
Proportion of participants with lower GI aGVHD(Through Days 60, 100 and 180 after HCT)
Proportion of participants with severe infections defined by NCI-CTCAE >= Grade 3(Through 100 and 180 days after HCT)
Number of deaths (relapse and nonrelapse-related)(Within 180, 365, and 730 days after HCT)
Proportion of participants with Grade III-IV aGVHD or death(Through Days 60, 100, and 180 days after HCT)
Proportion of participants with moderate to severe chronic GVHD(Within 180, 365, 545, and 730 days after HCT)
Proportion of participants 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(Through 365 days after HCT)
Time to GVHD relapse-free survival(Within 365 and 730 days after HCT)
Proportion of participants with relapse of primary malignancies(Through 180, 365, and 730 days after HCT)
Proportion of participants 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 participants 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)
Ctrough of 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)