A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase III Trial of Alpha 1 - Antitrypsin (AAT) Combined With Corticosteroids vs Corticosteroids Alone for the Treatment of High Risk Acute Graft-versus-Host Disease (GVHD) Following Allogeneic Hematopoietic Stem Cell Transplant
Overview
- Phase
- Phase 3
- Intervention
- Alpha-1 antitrypsin (AAT)
- Conditions
- Graft Versus Host Disease (GVHD)
- Sponsor
- CSL Behring
- Enrollment
- 136
- Locations
- 25
- Primary Endpoint
- Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
Study CSL964_5001 will investigate the efficacy of AAT with corticosteroids compared with corticosteroids alone as first line therapy for patients with high-risk acute GVHD
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients 12 years of age or older
- •Initial presentation of acute GVHD after allogeneic hematopoietic cell transplantation for any indication
- •Any graft or donor source or conditioning intensity
- •Clinical diagnosis of acute GVHD requiring systemic therapy with corticosteroids
Exclusion Criteria
- •Prior exogenous AAT exposure for GVHD prophylaxis
- •Relapsed, progressing, or persistent malignancy
- •de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
- •Receiving other drugs for the treatment of GVHD
- •Receiving systemic CS for any indication within 7 days before the onset of acute GVHD
Arms & Interventions
AAT
Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
Intervention: Alpha-1 antitrypsin (AAT)
Placebo
Albumin solution administered intravenously
Intervention: Placebo
Outcomes
Primary Outcomes
Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment
Time Frame: At Day 28
The overall response is defined as having a CR or PR at Day 28, along with: being alive, free of any next-line GVHD therapy, and free of escalation of prednisone-equivalent steroid dose to 2.5 milligrams per kilogram (mg/kg)/day or more. The percentage of participants with CR or PR is reported here. Wilson score confidence intervals (CIs) are reported here as a measure of dispersion. The CR was defined as a score of 0 for the GVHD staging in all evaluable organs. The PR was defined as an improvement in one or more organs involved with GVHD symptoms without progression in others. Acute GVHD was graded and assessed for response based on Harris (Mount Sinai Acute GVHD International Consortium \[MAGIC\]) criteria (stage 0, 1, 2, 3, 4) for skin, liver, upper gastrointestinal (GI) tract, and lower GI tract. Participants who had an escalation of prednisone-equivalent steroid dose to 2.5 mg/kg/day or higher were classified as non-responders (NR).
Secondary Outcomes
- Number of Participants With GVHD-free Survival(At Day 56)
- Incidence of Grade 2 to 3 Systemic Infections(Up to 90 days (including 30 days after last dose of study drug))
- Cumulative Incidence of Disease Relapse/ Progression of Primary Disease(At 6 months and 12 months)
- Percentage of Participants With Grade 3 to 5 Treatment-emergent Adverse Events (TEAEs)(Up to 30 days after the last dose of study drug)
- Cumulative Incidence of Chronic GVHD(At 6 and 12 months)
- Duration of Response (DOR)(Up to 12 months)
- Number of Participants With Non-relapse Mortality (NRM) Event(At 6 and 12 months)
- Number of Overall and Progression-free Survival Events(At 6 and 12 months)
- Percentage of Participants With Response(At Day 7, 14, 21, 28, 56, and 86)
- Percentage of Participants With Response Allowing for Approved Next-line Therapy(At Day 7, 14, 21, 28, 56, and 86)