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

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).

Time frame: At Day 28

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

Chronic GVHD was defined per National Institutes of Health (NIH) Consensus Criteria. Diagnosis of chronic GVHD of any severity (mild, moderate, or severe) was considered an event for this outcome measure, where death before cGVHD was treated as a competing risk.

Time frame: At 6 and 12 months

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

The cumulative incidence of relapse/progression of the primary disease, with death prior to relapse/progression treated as a competing risk. Death without prior relapse/progression was treated as a competing risk for relapse/progression.

Time frame: At 6 months and 12 months

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

The DOR was defined as time from the Day 28 response (CR or PR) until the first of the following events occurs: progression of acute GVHD, death, any next-line GVHD therapy, or escalation of prednisone-equivalent steroids to greater than or equal to (\>=) 2.5 mg/kg/day. Wald CIs are reported here as a measure of dispersion.

Time frame: Up to 12 months

Population: Analysis was performed on the ITT population participants with a response as defined in the measure description of the primary outcome measure. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

The cumulative incidence of Grade 2 to 3 systemic infections. Grade 2 to 3 systemic infections were defined according to the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Manual of Procedures.

Time frame: Up to 90 days (including 30 days after last dose of study drug)

Population: Analysis was performed on the safety population. The safety population included all randomized participants who received at least one dose of study treatment. Participants were classified according to the treatment received.

An event for overall survival (OS) was death from any cause, while an event for progression-free survival (PFS) was death from any cause or relapse/progression of the primary disease.

Time frame: At 6 and 12 months

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

GVHD-free survival was defined as participants being alive, free of acute or chronic GVHD, and free of any next-line GVHD therapy or escalation of steroids to \>=2.5 mg/kg/day prednisone or equivalent for treatment of GVHD.

Time frame: At Day 56

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

An event of NRM was death without prior evidence of relapse/progression of the primary disease, where relapse/progression was treated as a competing risk. Cumulative incidence of NRM at 6 and 12 months post-randomization is reported here for this outcome measure.

Time frame: At 6 and 12 months

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.

The incidence of Grade 3 to 5 TEAEs (per Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0). Wilson score CIs are reported here as a measure of dispersion.

Time frame: Up to 30 days after the last dose of study drug

Population: Analysis was performed on the safety population. The safety population included all randomized participants who received at least one dose of study treatment. Participants were classified according to the treatment received.

The percentage of participants with CR, PR (including subset with very good partial response \[VGPR\]), and treatment failure (TF). The designation of TF consisted of participants with NR, mixed response (MR) or progression. The initiation of additional systemic (next-line) GVHD therapies, escalation of prednisone equivalent steroid dose to \>= 2.5 mg/kg/day, or death from any cause prior to the assessment timepoint was also considered a TF. Simultaneous Goodman CIs are provided for category proportions for each arm at each assessment time.

Time frame: At Day 7, 14, 21, 28, 56, and 86

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered. Here, the 'number analyzed' for Day 86 includes responses for only those participants who remained on maintenance treatment after Day 28.

The percentage of participants with CR, PR (including subset with VGPR), and TF allowing for treatment with next-line therapy. The designation of TF consisted of participants with NR, MR, or progression. The escalation of prednisone-equivalent steroid dose to \>= 2.5 mg/kg/day or death from any cause prior to the assessment timepoint was also considered a TF. Simultaneous Goodman CIs are provided for category proportions for each arm at each assessment time.

Time frame: At Day 7, 14, 21, 28, 56, and 86

Population: Analysis was performed on the ITT population. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered. Here, the 'number analyzed' for Day 86 includes responses for only those participants who remained on maintenance treatment after Day 28.

The DOR was defined as time from the Day 28 response (CR or PR) until the first of the following events occurs: death, any next-line GVHD therapy, or escalation of prednisone-equivalent steroids to \>= 2.5 mg/kg/day. Wald CIs are reported here as a measure of dispersion.

Time frame: Up to 12 months

Population: Analysis was performed on the ITT population participants with a response as defined in the measure description of the primary outcome measure. The ITT population consisted of all randomized participants, classified according to their randomized treatment assignments. All randomized participants were included, regardless of whether the assigned study treatment was truly administered.