A Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD

A Multicenter, Randomized, Double-blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of CYP-001 in Combination With Corticosteroids vs Corticosteroids Alone for the Treatment of High-Risk Acute Graft Versus Host Disease

This study is a prospective randomized placebo-controlled phase 2 study to compare CYP-001 plus corticosteroids (CS) to placebo plus CS in allogeneic hematologic stem cell transplant recipients with HR-aGvHD. Severity of GvHD will be assessed at screening and throughout the study using Mount Sinai Acute GvHD International Consortium (MAGIC) guidelines. Eligible subjects will be randomized to receive either CYP-001 IV infusion on Days 0 and 4 or placebo on the same days. All subjects will receive ongoing CS therapy as appropriate per institutional guidelines. Subjects will have study visits up to Day 100 during the Primary Evaluation Period. During the Follow-Up Period, subjects will have study visits up to 24 months.

Inclusion Criteria:

• Undergone allogeneic hematopoietic stem cell transplant (HSCT)
• Clinically diagnosed with acute GvHD requiring systemic therapy with corticosteroids.
• HR-aGvHD must meet one of the following clinical features within 72 hours prior to randomization: (a) high-risk as per Refined Minnesota Criteria; OR (b) One of the following: (i) isolated stage 2 involvement of the lower GI tract; (ii) Stage 1 lower GI tract disease with skin involvement
• Evidence of myeloid engraftment post allogeneic HSCT
• Life expectancy of at least one month

Exclusion Criteria:

• Received any systemic treatment for aGvHD other than corticosteroids +/- calcineurin inhibitors
• Chronic GvHD or overlap syndrome with both acute and chronic features of GvHD
• Relapsed primary malignancy since
• received more than one allogeneic HSCT
• Clinically significant respiratory, renal or cardiac disease
• Cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver
• Any active uncontrolled infection requiring treatment and likely to impact on the ability of the subject to participate in the trial.
• Known infection with CMV, EBV, HHV-6, HBV, HCV, HIV or Tuberculosis. If the treatment for CMV, EBV, HHV-6, HBV, HCV has commenced the subject is eligible.
• Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-001.
• Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.