Graft vs Host DiseasePhase 1NCT02923375
A Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease
A Phase 1 study testing Mesenchymoangioblast-derived mesenchymal stem cells in people with Graft vs Host Disease, run by Cynata Therapeutics Limited at 7 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graft vs Host Disease
- What is being tested?
- Mesenchymoangioblast-derived mesenchymal stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 1 Mar 2017to 30 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United Kingdom5 sites
NHS Foundation Trust
Bristol
NHS Trust
Leeds
NHS Foundation Trust
Liverpool
NHS Foundation Trust
Manchester
NHS Foundation Trust
Nottingham
Australia2 sites
Royal Adelaide Hospital
Adelaide, South Australia
Sydney Local Health District
Sydney, New South Wales
About this study
Official title: 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.
Read the 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.
- Conditions
- Graft vs Host Disease
- Being tested
- Mesenchymoangioblast-derived mesenchymal stem cells
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymoangioblast-derived mesenchymal stem cellsBiological
Also called CYP-001
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | 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) Receives: Biological: Mesenchymoangioblast-derived mesenchymal stem cells |
| Cohort B | Experimental | 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) Receives: Biological: Mesenchymoangioblast-derived mesenchymal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment emergent adverse events [safety and tolerability]
Safety
Measured: 28 days
Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability]
Safety
Measured: 100 days
Secondary outcomes (6)
Complete Response by Day 28
Proportion of participants who show a Complete Response (absence of any signs or symptoms of GvHD) by Day 28
Measured: 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
Measured: 28 days
Overall Survival at Day 28
Proportion of participants who survive until Day 28
Measured: 28 days
Complete Response by Day 100
Proportion of participants who show a Complete Response by Day 100
Measured: 100 days
Partial Response by Day 100
Proportion of participants who show a Partial Response by Day 100
Measured: 100 days
Overall Survival at Day 100
Proportion of participants who survive until Day 100
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2016 (estimated)
- Study start1 Mar 2017
- Primary completion28 Aug 2018
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cynata Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kilian Kelly, PhD, Study director, Cynata Therapeutics Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02923375
- Sponsor's protocol ID
- CYP-GvHD-P1-01
- Other IDs
- 2016-000070-38, 2016
- Status last verified
- Aug 2020
- First submitted
- 3 Oct 2016
- Last updated
- 11 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kelly K, Bloor AJC, Griffin JE, Radia R, Yeung DT, Rasko JEJ. Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease. Nat Med. 2024 Jun;30(6):1556-1558. doi: 10.1038/s41591-024-02990-z. Epub 2024 May 22.
PubMed 38778211Bloor 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.
PubMed 32929265
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02923375
- Acronym / sponsor ID
- CYP-GvHD-P1-01
- Conditions
- Graft vs Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Cynata Therapeutics LimitedIndustry (pharma, biotech, devices)
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 28 Aug 2018 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 4 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Biological: Mesenchymoangioblast-derived mesenchymal stem cellsMesenchymoangioblast-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) |
| Cohort B | Experimental | Biological: Mesenchymoangioblast-derived mesenchymal stem cellsMesenchymoangioblast-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) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymoangioblast-derived mesenchymal stem cellsAlso: CYP-001The 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. | Biological | Cohort A, Cohort B |
Primary outcome
Incidence and severity of treatment emergent adverse events [safety and tolerability]
Time frame: 28 days
Safety
Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability]
Time frame: 100 days
Safety
6 secondary outcomes
Complete Response by Day 28
Time frame: 28 days
Partial Response by Day 28
Time frame: 28 days
Overall Survival at Day 28
Time frame: 28 days
Complete Response by Day 100
Time frame: 100 days
Partial Response by Day 100
Time frame: 100 days
Overall Survival at Day 100
Time frame: 100 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Derived from this study: PubMed 38778211Kelly K, Bloor AJC, Griffin JE, Radia R, Yeung DT, Rasko JEJ. Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease. Nat Med. 2024 Jun;30(6):1556-1558. doi: 10.1038/s41591-024-02990-z. Epub 2024 May 22.
- Derived from this study: PubMed 32929265Bloor 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.
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kilian Kelly, PhD study director
Cynata Therapeutics Limited
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mesenchymoangioblast-derived mesenchymal stem cells in people with Graft vs Host Disease, run by Cynata Therapeutics Limited at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of treatment emergent adverse events [safety and tolerability] (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02923375, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.