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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Graft Versus Host Disease, Acute

Intervention / Treatment
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* Biological: CYP-001: Cymerus induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs)
* Biological: Placebo
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYP-001 plus corticosteroids<br> | Biological: CYP-001: Cymerus induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs)<br>* Cymerus MSCs are derived from iPSCs using the proprietary Cymerus platform technology.<br>Drug: Corticosteroids<br>* All enrolled subjects in this trial must receive corticosteroids at a minimum dose of oral prednisone 2 mg/kg/day (or methylprednisolone 1.6 mg/kg/day IV) as therapy for aGvHD for at least for 72 hours post enrollment.<br>|
| Placebo Comparator: Placebo plus corticosteroids<br> | Biological: Placebo<br>* The placebo product is identical to CYP-001, except that it contains no active agent<br>Drug: Corticosteroids<br>* All enrolled subjects in this trial must receive corticosteroids at a minimum dose of oral prednisone 2 mg/kg/day (or methylprednisolone 1.6 mg/kg/day IV) as therapy for aGvHD for at least for 72 hours post enrollment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | ORR is defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durable Overall response rate (ORR) | Durable ORR is defined as the proportion of subjects demonstrating OR at Day 28 and maintaining OR at Day 60 and Day 100 | 100 days | 
| Overall response rate (ORR) | ORR is defined as the proportion of subjects demonstrating a CR or PR without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse. | 100 days | 
| Complete response rate (CRR) | ORR is defined as the proportion of subjects demonstrating a CR without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse. | 100 days | 
| Overall survival | The Kaplan Meier curve will be used to estimate the distribution of overall survival and the probability of surviving to relevant timepoints. | 2 years | 
| Event-free survival | Event-Free survival is defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. | 2 years | 
| Time to non-relapse mortality | Time to non-relapse mortality is defined as the time from the date of randomization to the date of death not preceded by hematologic disease relapse/progression. | 2 years | 
| Failure-free survival | Failure-free survival is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment | 2 years | 
| Time to malignancy relapse/progression | Time to malignancy relapse/progression is defined as the time from the date of randomization to the date to hematologic malignancy relapse/progression. | 2 years | 
| Incidence of chronic GvHD | Chronic GvHD is defined as the diagnosis of mild, moderate, or severe chronic GvHD. | 2 years | 
| Weekly cumulative steroid dose | The total corticosteroid dose administered each week | 100 days | 
| Patient reported outcomes: Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) instrument | The FACT-BMT form was designed to measure the quality of life in patients undergoing bone marrow transplantation. | 2 years | 
| Patient reported outcomes: EuroQol 5-Dimension (EQ-5D) health-related quality of life instrument | EQ-5D is a standardized measure of health-related quality of life | 2 years | 
| Incidence, severity, duration of treatment-emergent adverse events | Assessment of safety | 2 years |