A phase 2 study to investigate the efficacy and safety of CYP‑001 in combination with corticosteroids in adults with high-risk acute graft versus host disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cynata Therapeutics Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Jul 2024 → ongoing

Decision date (initial)

2024-03-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Cynata Therapeutics Limited

External identifiers

EU CT number

2022-502673-41-01

WHO UTN

U1111-1287-2412

ClinicalTrials.gov

NCT05643638

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of CYP 001 and steroids vs placebo and steroids in adults with HR-aGvHD based on Overall Response Rate at Day 28

Secondary objectives 10

1. To assess additional responses and long-term efficacy outcomes
2. To assess Overall Survival (OS)
3. To assess Event-Free survival (EFS)
4. To assess Non-Relapse Mortality (NRM)
5. To assess Failure Free Survival (FFS)
6. To assess the incidence of relapse/progression of the underlying hematologic disease for which allogeneic HSCT was performed
7. To measure the incidence of chronic GvHD
8. To assess the cumulative steroid dose until Day 100
9. To evaluate changes in Subject Reported Outcomes
10. To evaluate the safety and tolerability of CYP 001 in subjects with aGvHD

Conditions and MedDRA coding

High-Risk Acute Graft Versus Host Disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Paul Ehrlich Institute, Federal Agency For Medicines And Health Products, European Medicines Agency, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female subjects 18 years of age or older
2. Provide written informed consent form and agree to comply with study procedures
3. Have undergone first allogeneic hematopoietic stem cell transplant (HSCT) to treat a hematologic disease (malignant or non- malignant), from any donor source (matched and mismatched) using bone marrow, peripheral blood stem cells, or cord blood and any conditioning intensity
4. Have been clinically diagnosed with acute GvHD requiring systemic therapy with CS. Patients can be enrolled with only a clinically established diagnosis. Biopsy of involved organs with acute GvHD is encouraged but is not required and should not delay study entry. Enrollment/randomization includes commitment to continue steroids
5. HR-aGvHD must meet one of the following clinical features within 72 hours prior to randomization: A. High-risk as per Refined Minnesota Criteria: • Single organ involvement o Stage 4 skin o Stage 3-4 lower GI o Stage 1-4 liver • Multiple organ involvement o Stage 1-2 lower GI plus any liver o Stage 2 lower GI plus any skin o Stage 3-4 lower GI plus any liver or skin o Any three organ involvement OR B. One of the following: • Isolated stage 2 involvement of the lower GI tract • Stage 1 lower GI tract disease with skin involvement
6. Evidence of myeloid engraftment post allogeneic HSCT defined as three (3) consecutive days of achieving sustained ANC >500 x 10^6/L. Use of G-CSF and blood transfusion is allowed.
7. Life expectancy of at least one month, in the opinion of the investigator.
8. Investigator believes that the subject (or the subject’s legally acceptable representative[s]) understands the nature, scope and possible consequences of the study.

Exclusion criteria 16

1. Has received any systemic treatment for aGvHD other than corticosteroids +/- CNI (prophylaxis or treatment). Treatment with CS is allowed for up to 72 hours prior to Day 0.
2. Clinical presentation of chronic GvHD or overlap syndrome with both acute and chronic features of GvHD
3. Presence of relapsed primary malignancy since allogeneic HSCT
4. Have received more than one allogeneic HSCT
5. Clinically significant respiratory, renal or cardiac disease at screening including any of the following: a. requiring mechanical ventilation or having resting SO2 <90% on pulse oximetry b. serum creatinine >2mg/dL or eGFR <30ml/min (Cockroft Gault equation) c. uncontrolled hypertension d. Congestive heart failure New York Heart Association Class III or IV
6. Presence of cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver defined as persistent bilirubin abnormalities not attributable to aGvHD
7. Presence of any active uncontrolled infection requiring treatment and which in the opinion of the Investigator and/or Study medical monitor is likely to impact on the ability of the subject to participate in the trial. Infections are considered controlled if appropriate therapy has been used and, at the time of screening, no signs of progression are present.
8. Known infection with CMV, EBV, HBV, HCV, HIV or Tuberculosis. If the treatment for CMV, EBV, HBV, HCV has commenced the subject is eligible for study.
9. Any other medical or psychiatric condition which, in the opinion of the Investigator and/or Study medical monitor, makes the subject unsuitable for participation in the study or interfere with interpretation of study data.
10. Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-001.
11. Known or suspected current alcohol or substance abuse problem, in the opinion of the investigator.
12. Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.
13. Female subject of childbearing potential either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 6 months after receipt of the last dose of investigational product. All female subjects are assumed to be of childbearing potential except: • Subjects aged > 60 years and postmenopausal. • Subjects aged 45 to 60 years (inclusive) with amenorrhea for ≥ 1 year with documented evidence of follicle-stimulating hormone level > 30 IU/L. If the follicle-stimulating hormone value is not available before randomization, a urine pregnancy test is required. • Subjects who are surgically sterile for at least 3 months before providing informed consent.
14. Pregnant, breastfeeding or not willing to cease breastfeeding.
15. Currently receiving a therapy not permitted during the study.
16. Involved in the planning and / or conduct of the study (applies to Cynata Therapeutics Limited staff, staff at the study site, and third-party vendors).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Response Rate at Day 28 is defined as the proportion of participants in each treatment arm demonstrating a complete response (CR; resolution of aGvHD signs and symptoms) or a partial response (PR; an improvement in the severity of GvHD by at least one grade compared to baseline) without requirement for additional systemic therapies for an earlier progression, a mixed response or a lack of response.

Secondary endpoints 9

1. Proportion of all subjects in each treatment arm with durable overall response (OR) defined as patients with OR (CR or PR) at Day 28 and maintain an OR at Day 60 and Day 100; Proportion of all subjects in each treatment arm with OR defined as subjects with complete response (CR) or partial response (PR) at Day 7, Day 14, Day 21, Day 60 and Day 100; Proportion of all subjects in each treatment arm with CR at Day 28, Day 60 and Day 100
2. Overall Survival (OS) is defined as the time from date of randomization to the date of death due to any cause
3. Event-Free survival (EFS) is defined as the time from the date of randomization (baseline) to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
4. Time to Non-Relapse Mortality (NRM) is defined as the time from the date of randomization (baseline) to the date of death not preceded by hematologic disease relapse/progression.
5. Failure Free Survival (FFS) is defined as the time from the date of randomization (baseline) to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment; Hematologic disease Relapse/Progression is defined as the time from the date of randomization (baseline) to the date to hematologic disease (malignant or non-malignant) relapse/progression.
6. cGvHD is defined as the diagnosis of mild, moderate, or severe cGvHD
7. Weekly cumulative steroid dose for each subject up to Day 100 or end of treatment will be calculated
8. Changes in Patient Reported Outcomes (PRO)
9. To evaluate the incidence, severity, duration of TEAE, changes from baseline in hematology, biochemistry, coagulation profile

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cynata Therapeutics Limited

Sponsor organisation

Cynata Therapeutics Limited

Address

P. O. Box 7165 Hawthorn North

City

Melbourne

Postcode

VIC 3122

Country

Australia

Scientific contact point

Organisation

Cynata Therapeutics Limited

Contact name

Kilian Kelly

Public contact point

Organisation

Cynata Therapeutics Limited

Contact name

Kilian Kelly

Third parties 5

Locations

4 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications