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

Graft Versus Host Disease, Acute Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05643638
• Other study ID #: CYP-GvHD-P2-01
• Status: Recruiting
• Phase: Phase 2
• Start date: March 4, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Cynata Therapeutics Limited
• Contact: Cynata Project Manager
• Phone: +61 3 7067 6940
• Email: clinical[@]cynata.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2026
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Disease
• Graft Versus Host Disease, Acute
• Graft vs Host Disease

Intervention

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
The placebo product is identical to CYP-001, except that it contains no active agent

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.

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Turkey	Anadolu Medical Center	Eskisehir
Turkey	Gayrettepe Florence Nightingale Hastanesi	Istanbul
Turkey	Koc University	Istanbul
Turkey	Memorial Bahcelievler Hospital	Istanbul
Turkey	Izmir Medicalpark Hospital	Izmir
Turkey	Inonu University	Malatya
Turkey	Dr Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Yenimahalle
United States	Northwestern University	Evanston	Illinois
United States	University of Arkansas Medical Center	Little Rock	Arkansas
United States	Weill Cornell Medicine - New York Presbyterian Hospital	New York	New York
United States	University Of Nebrasaka Medical Center	Omaha	Nebraska
United States	Memorial healthcare System	Pembroke Pines	Florida
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Cynata Therapeutics Limited

Countries where clinical trial is conducted

United States,  Australia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of chronic GvHD	Chronic GvHD is defined as the diagnosis of mild, moderate, or severe chronic GvHD.	2 years
Secondary	Weekly cumulative steroid dose	The total corticosteroid dose administered each week	100 days
Secondary	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
Secondary	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
Secondary	Incidence, severity, duration of treatment-emergent adverse events	Assessment of safety	2 years