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

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

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.

Study Overview

• Status: Completed
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Biological: Mesenchymoangioblast-derived mesenchymal stem cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • Sydney Local Health District
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
• United Kingdom
  • Bristol, United Kingdom
    • NHS Foundation Trust
  • Leeds, United Kingdom
    • NHS Trust
  • Liverpool, United Kingdom
    • NHS Foundation Trust
  • Manchester, United Kingdom
    • NHS Foundation Trust
  • Nottingham, United Kingdom
    • NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; 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; 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.; Other Names: CYP-001
Experimental: Cohort B; 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; 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.; Other Names: CYP-001

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cynata Therapeutics Limited
• Investigators: Study Director: Kilian Kelly, PhD, Cynata Therapeutics Limited

Publications and helpful links

General Publications

• Bloor AJC, Patel A, Griffin JE, Gilleece MH, Radia R, Yeung DT, Drier D, Larson LS, Uenishi GI, Hei D, Kelly K, Slukvin I, Rasko JEJ. Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nat Med. 2020 Nov;26(11):1720-1725. doi: 10.1038/s41591-020-1050-x. Epub 2020 Sep 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): August 28, 2018
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: October 3, 2016
• First Submitted That Met QC Criteria: October 3, 2016
• First Posted (Estimate): October 4, 2016

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 8, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: CYP-GvHD-P1-01; 2016-000070-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes