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.

Study Overview

• Status: Recruiting
• Conditions: Graft Versus Host Disease, Acute
• Intervention / Treatment: Drug: Corticosteroids; Biological: Placebo; Biological: CYP-001: Cymerus induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cynata Project Manager; Phone Number: +61 3 7067 6940; Email: clinical@cynata.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Recruiting
      • Royal Brisbane and Women'S Hospital
• Turkey
  • Eskişehir, Turkey
    • Recruiting
    • Anadolu Medical Center
  • Istanbul, Turkey
    • Recruiting
    • Koç University
  • Istanbul, Turkey, 34318
    • Recruiting
    • Gayrettepe Florence Nightingale Hastanesi
  • Istanbul, Turkey
    • Recruiting
    • Memorial Bahcelievler Hospital
  • Izmir, Turkey
    • Recruiting
    • Izmir Medicalpark Hospital
  • Malatya, Turkey
    • Recruiting
    • Inonu University
  • Yenimahalle, Turkey
    • Recruiting
    • Dr Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas Medical Center
  • Florida
    • Pembroke Pines, Florida, United States, 33026
      • Recruiting
      • Memorial Healthcare System
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Recruiting
      • Northwestern University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University Of Nebrasaka Medical Center
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine - New York Presbyterian Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYP-001 plus corticosteroids	Drug: Corticosteroids; 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.; Biological: CYP-001: Cymerus induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs); Cymerus MSCs are derived from iPSCs using the proprietary Cymerus platform technology.
Placebo Comparator: Placebo plus corticosteroids	Drug: Corticosteroids; 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.; Biological: Placebo; The placebo product is identical to CYP-001, except that it contains no active agent

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cynata Therapeutics Limited
• Investigators: Study Director: Jolanta Airey, MD, Cynata Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 29, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Disease Attributes; Acute Disease; Graft vs Host Disease
• Other Study ID Numbers: CYP-GvHD-P2-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Sponsor will consider requests to share IPD from this study for further research of a non-commercial nature. Requests should be submitted to clinical@cynata.com. Sharing of IPD will be subjects to the execution of an IPD sharing agreement, and applicable laws, regulations and guidance in force at that time.
• IPD Sharing Time Frame: IPD sharing requests will be considered from 12 months after publication of results of this study.
• IPD Sharing Access Criteria: Requests for sharing of IPD for non-commercial research purposes will be considered in good faith by the Sponsor. Requests must be accompanied by a detailed research plan, with a justification for the proposed research.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No