A Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.

Detailed Description
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This is a multi-centre, open label, dose escalation study to assess the safety, tolerability and efficacy of two infusions of CYP-001, in adults who have steroid-resistant GvHD. Participants will receive standard of care treatment throughout the study, according to local procedures. The first eight participants will be enrolled in Cohort A and receive a CYP-001 dose of 1 million cells per kg, up to a maximum dose of 100 million cells, on Day 0 and Day 7. Subject to a safety review of data from Cohort A, an additional eight participants will be enrolled into Cohort B and receive a CYP-001 dose of 2 million cells/kg, up to a maximum dose of 200 million cells, on Day 0 and Day 7. The primary evaluation period concludes for each participant 100 days after the first dose of CYP-001. Participants will have study visits on Days 0, 3, 7, 14, 21, 28, 60 and 100. Subsequently, participants will enter a long term follow-up period, which concludes 2 years after the first dose of CYP-001.

Official Title
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An Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease

Conditions
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Graft vs Host Disease

Intervention / Treatment
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* Biological: Mesenchymoangioblast-derived mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis using consensus grading with steroid-resistant Grade II-IV acute GvHD, after a haematopoietic stem cell transplant for a haematological disorder. Life expectancy of at least one month. Agree to have follow-up data collected for two years after their initial dose of CYP-001 (under a separate protocol). Exclusion Criteria: Pregnant or breastfeeding or plan to become pregnant within three months of receiving their last dose of CYP-001. Have received any investigational research agent within 30 days or five half-lives (whichever is longer) prior to the first dose of IMP. Known or suspected current alcohol or substance abuse problem. Progressive or relapsing haematological malignancy, a current solid tumour, or previous malignant solid tumour that is likely to recur during the period of the study (with the exception of a past history of basal or squamous cell carcinomas). Heart failure (NYHA Functional Class II-IV) and/or pulmonary failure. Haemodynamically unstable and/or at high risk of cardiovascular events. Terminal organ failure. Meningitis, pneumonia with hypoxemia, HIV or another severe or uncontrolled systemic infection, which in the opinion of the investigator is likely to impact on the ability of the patient to participate in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 1 million cells/kg (up to a maximum of 100 million cells) by IV infusion on two occasions (Day 0 and Day 7) | Biological: Mesenchymoangioblast-derived mesenchymal stem cells<br>* The active agent in CYP-001 is allogeneic mesenchymoangioblast-derived mesenchymal stem cells (MCA-derived MSCs), which are produced using the proprietary Cymerus™ platform technology. Cymerus™ refers to the process of generating cell-based products from intermediate cells, MCAs, which in turn are derived from induced pluripotent stem cells or iPSCs. The iPSCs used in the Cymerus™ process were derived from blood donated by a fully-consented healthy adult donor, and were reprogrammed using a transgene-free, viral-free and feeder-free technique.<br>* Other names: CYP-001;|
| Experimental: Cohort B<br>Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 2 million cells/kg (up to a maximum of 200 million cells) by IV infusion on two occasions (Day 0 and Day 7) | Biological: Mesenchymoangioblast-derived mesenchymal stem cells<br>* The active agent in CYP-001 is allogeneic mesenchymoangioblast-derived mesenchymal stem cells (MCA-derived MSCs), which are produced using the proprietary Cymerus™ platform technology. Cymerus™ refers to the process of generating cell-based products from intermediate cells, MCAs, which in turn are derived from induced pluripotent stem cells or iPSCs. The iPSCs used in the Cymerus™ process were derived from blood donated by a fully-consented healthy adult donor, and were reprogrammed using a transgene-free, viral-free and feeder-free technique.<br>* Other names: CYP-001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment emergent adverse events [safety and tolerability] | Safety | 28 days | 
| Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability] | Safety | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response by Day 28 | Proportion of participants who show a Complete Response (absence of any signs or symptoms of GvHD) by Day 28 | 28 days | 
| Partial Response by Day 28 | Proportion of participants who show a Partial Response (improvement in the severity of GvHD by at least one grade compared to baseline) by Day 28 | 28 days | 
| Overall Survival at Day 28 | Proportion of participants who survive until Day 28 | 28 days | 
| Complete Response by Day 100 | Proportion of participants who show a Complete Response by Day 100 | 100 days | 
| Partial Response by Day 100 | Proportion of participants who show a Partial Response by Day 100 | 100 days | 
| Overall Survival at Day 100 | Proportion of participants who survive until Day 100 | 100 days |