Phase 3 N=136 Randomized Double-blind Treatment

Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone

Graft Versus Host Disease (GVHD)

Bottom Line

View on ClinicalTrials.gov: NCT04167514 ↗

Enrolled (actual)

136

Serious AEs

25.8%

Results posted

Aug 2025

Primary outcome: Primary: Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment — 60.0; 45.1 percentage of participants — p=0.034

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Alpha-1 antitrypsin (AAT) (Biological); Placebo (Drug)
Age: Pediatric, Adult, Older Adult · 12+ yrs
Sex: All
Sponsor: CSL Behring
Primary completion: Sep 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment	60.0; 45.1	0.034 sig
SECONDARY Duration of Response (DOR)	82; 154	—
SECONDARY Number of Participants With Non-relapse Mortality (NRM) Event	12; 14; 13; 14	—
SECONDARY Number of Overall and Progression-free Survival Events	16; 18; 20; 23; 25; 28	—
SECONDARY Number of Participants With GVHD-free Survival	29; 25	—
SECONDARY Percentage of Participants With Response	29.2; 33.8; 33.8; 25.4; 36.9; 40.8	—
SECONDARY Percentage of Participants With Response Allowing for Approved Next-line Therapy	29.2; 33.8; 36.9; 31.0; 33.8; 35.2	—
SECONDARY Incidence of Grade 2 to 3 Systemic Infections	20; 22	—
SECONDARY Percentage of Participants With Grade 3 to 5 Treatment-emergent Adverse Events (TEAEs)	46.0; 65.2	—
SECONDARY Cumulative Incidence of Chronic GVHD	13; 9; 20; 14	—
SECONDARY Cumulative Incidence of Disease Relapse/ Progression of Primary Disease	14; 14; 15; 15	—

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

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04167514). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.