Peripheral Arterial DiseasePhase 1NCT01916369
Safety Trial Of CTX Cells In Patients With Lower Limb Ischaemia
A Phase 1 study testing CTX DP in people with Peripheral Arterial Disease, run by ReNeuron Limited at 1 site in United Kingdom.
Trial summary
The primary objective of the Phase I ascending dose trial is to investigate the safety and tolerability of intramuscular (gastrocnemius) injections of human neural stem cell product, CTX, in patients with peripheral arterial disease (Fontaine Stage II through IV). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- CTX DP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2014to 16 Jan 2018
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated written informed consent obtained from the patient.
- Peripheral arterial occlusive disease due to atherosclerosis (Fontaine stages II, III or IV) of one leg or both defined as
- Fontaine stage II: Intermittent claudication
- Fontaine stage III: Rest pain
- Fontaine stage IV: Ischaemic ulcer or (dry) gangrene
- Patients unsuitable for surgical re-vascularisation
Show all 11Show fewer
- An ABPI of <0.9 or a toe/brachial index of <0.7
- Age >50 years
- Males or Females. Women must be surgically sterile or more than 2 years post their last menstrual period and with a negative pregnancy test.
- Smoker or non-smoker
- Diabetics and non-diabetics provided HbA1c <8% (or 64 mmol/mol)
Who cannot join
- Estimated survival of less than 6 months.
- Infection of the involved extremity manifested by fever, purulence, or severe cellulitis or active wet gangrenous tissue wound with exposed tendon or bone.
- Failed ipsilateral revascularisation procedure within 8 weeks prior to enrolment (defined as failure to restore adequate circulation, i.e., the procedure did not achieve an increase in ABPI of 0.15 or more, substantial improvement in Pulse Volume Recording, or clinical improvement).
- Previous amputation of the talus or above in the target limb.
- Planned major amputation within one month of planned date for injection of study medication (CTX DP).
- Anticoagulants including heparin, warfarin or analogues within the past month unless these can be discontinued per protocol for seven days prior to injection and two days post injection in the case of warfarin or one day prior to injection and two days post injection in the case of heparin or other anticoagulants.
Show all 21Show fewer
- A history of deep vein thrombosis in either leg.
- Previous treatment with systemic growth pro-angiogenic factors or with stem-cell therapy.
- Ulcers from venous or neuropathic origin.
- Uncontrolled blood pressure defined as sustained systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg on repeated measures on different days.
- Acute cardiovascular events (e.g., myocardial infarction, stroke, recent coronary intervention) up to 6 months prior to enrolment.
- Previous or present history of malignant disease (except basal-cell carcinoma and cervical carcinoma in situ, which was removed without recurrence more than 5 years prior to enrolment).
- Body mass index >35.
- Previously diagnosed as clinically immune-compromised or taking systemic immunosuppressant medication.
- Patients taking sodium valproate for any indication within the past week.
- Organ transplant recipient.
- Inability to comprehend consent information or unlikely to comply with study requirements
- Participation in another study involving an Investigational Medicinal Product within the 3 months or 5 half-lives of the product (whichever is longer) prior to enrolment.
- Drug or alcohol abuse.
- Any other significant disease or abnormalities likely to impact study compliance or interpretation of the results. (If in doubt consult with the ReNeuron study monitor).
- Patients taking tamoxifen or analogues.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Ascending Dose Safety Study Of Intramuscular CTX0E03 In Patients With Lower Limb Ischaemia
The primary objective of the Phase I ascending dose trial is to investigate the safety and tolerability of intramuscular (gastrocnemius) injections of human neural stem cell product, CTX, in patients with peripheral arterial disease (Fontaine Stage II through IV). This trial is based on independent preclinical data from a leading academic research institution that has been submitted for publication. Inclusion of patients with Fontaine Stage II is justified as these patients have a lower incidence of background events and will facilitate distinction between events which are possibly intervention-related versus spontaneous events associated with underlying advanced atherosclerosis. The trial is designed to treat 9-18 patients and evaluate safety measures over a 12 month follow-up period.
Read the detailed description
Design: The trial is a multi-centre open label, non-comparative, ascending dose safety study, using CTX cells to treat patients with lower limb ischaemia, with follow-up over 12 months.
Pre-treatment selection of patients: Men and women, aged >50 years with peripheral arterial occlusive disease (Fontaine Stage II through IV) of one leg or both, unsuitable for surgical re-vascularisation, an ankle/brachial pressure index (ABPI) of <0.9 or a toe/brachial index of <0.7. Women must be surgically sterile or more than 2 years past their last menstrual period and test negative for pregnancy.
Treatment: One patient will be treated at one time with a single dose of CTX cells. Three ascending doses (20, 50 or 80 million cells), allocated sequentially, will be tested in 9-18 patients (3 dose cohorts of 3-6 patients. All trial patients will receive 10 intramuscular injections of CTX DP into the gastrocnemius muscle of their ischaemic leg on a single occasion. In the event that both legs have peripheral arterial disease, the injections will be administered to the leg determined by the Investigator to have the more advanced/severe disease provided that leg has not already had surgical amputation of toes or above.
A minimum interval of 28 days will be observed between dosing the first and second patient and 7 days between dosing subsequent patients in a given cohort in order to assess the safety and tolerability of CTX DP at that dose. A further 3 patients may be added to any cohort (to a maximum of 18 of total treated patients) at the discretion of the Data Safety Monitoring Board (DSMB) if required to further clarify the safety profile). A minimum interval of 28 days will be observed between dosing the first and second patient and 7 days between dosing subsequent patients in a given cohort in order to assess the safety and tolerability of CTX DP at that dose.
Post-treatment follow-up: There will be 8 scheduled visits to the clinic for monitoring over the 12 month follow-up period.
End-points: The primary endpoint of the trial is safety, measured by numbers of relevant adverse events, health screening, physical examination (overall and of the treated limb), immunological response, amputation and concomitant medications in the first year after treatment.
Post-trial follow-up: Life-long annual follow-up to record any new cancer via national cancer registry or similar system or by Investigator or family practitioner (as permitted by competent authorities, ethics committees and informed consent).
- Conditions
- Peripheral Arterial Disease
- Being tested
- CTX DP
- Keywords
- Peripheral Arterial Disease, Fontaine Stage II, III or IV, Vascular disease, Cardiovascular diseases, Neural stem cell
- Medical subject headings
- Peripheral Arterial Disease, Vascular Diseases, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTX DPBiological
Also called CTX0E03
Single dose treatment consisting of 10 injections (20, 50 or 80 million cells) into the gastrocnemius muscle near to the damaged area
| Study group | Role | What they receive |
|---|---|---|
| CTX DP | Experimental | Human neural stem cell product, single dose administered once only, increasing doses Receives: Biological: CTX DP |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of adverse events
Monitoring of medical history, general physical examination, physical examination of the ipsilateral leg (inflammation, infection, swelling, tenderness, ulceration, gangrene), temperature, pulse rate and rhythm, ECG, blood pressure, full blood count, liver function tests, serum urea and electrolytes, creatine phosphokinase(muscle isoform), immunological response to CTX, amputation and concomitant medication.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2013 (estimated)
- Study startApr 2014
- Primary completion16 Jan 2018
- Study completion16 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- ReNeuron Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jill JF Belch, MBChB, Principal investigator, Ninewells Hospital Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01916369
- Sponsor's protocol ID
- RN09-CP-0001
- Other IDs
- 2011-005810-13
- Status last verified
- Jan 2018
- First submitted
- 2 Aug 2013
- Last updated
- 31 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of Content, Stoichiometry and Transfer of miRNA from Human Neural Stem Cell Line Derived Exosomes. PLoS One. 2016 Jan 11;11(1):e0146353. doi: 10.1371/journal.pone.0146353. eCollection 2016.
PubMed 26752061
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Ascending Dose Safety Study Of Intramuscular CTX0E03 In Patients With Lower Limb Ischaemia
- ClinicalTrials.gov ID
- NCT01916369
- Acronym / sponsor ID
- RN09-CP-0001
- Conditions
- Peripheral Arterial Disease
- Keywords
- Peripheral Arterial Disease, Fontaine Stage II, III or IV, Vascular disease, Cardiovascular diseases, Neural stem cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- ReNeuron LimitedIndustry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- 16 Jan 2018 (actual)
- Study completion
- 16 Jan 2018 (actual)
- First posted
- 5 Aug 2013 (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 primary objective of the Phase I ascending dose trial is to investigate the safety and tolerability of intramuscular (gastrocnemius) injections of human neural stem cell product, CTX, in patients with peripheral arterial disease (Fontaine Stage II through IV). This trial is based on independent preclinical data from a leading academic research institution that has been submitted for publication. Inclusion of patients with Fontaine Stage II is justified as these patients have a lower incidence of background events and will facilitate distinction between events which are possibly intervention-related versus spontaneous events associated with underlying advanced atherosclerosis. The trial is designed to treat 9-18 patients and evaluate safety measures over a 12 month follow-up period.
Detailed description
Design: The trial is a multi-centre open label, non-comparative, ascending dose safety study, using CTX cells to treat patients with lower limb ischaemia, with follow-up over 12 months.
Pre-treatment selection of patients: Men and women, aged >50 years with peripheral arterial occlusive disease (Fontaine Stage II through IV) of one leg or both, unsuitable for surgical re-vascularisation, an ankle/brachial pressure index (ABPI) of <0.9 or a toe/brachial index of <0.7. Women must be surgically sterile or more than 2 years past their last menstrual period and test negative for pregnancy.
Treatment: One patient will be treated at one time with a single dose of CTX cells. Three ascending doses (20, 50 or 80 million cells), allocated sequentially, will be tested in 9-18 patients (3 dose cohorts of 3-6 patients. All trial patients will receive 10 intramuscular injections of CTX DP into the gastrocnemius muscle of their ischaemic leg on a single occasion. In the event that both legs have peripheral arterial disease, the injections will be administered to the leg determined by the Investigator to have the more advanced/severe disease provided that leg has not already had surgical amputation of toes or above.
A minimum interval of 28 days will be observed between dosing the first and second patient and 7 days between dosing subsequent patients in a given cohort in order to assess the safety and tolerability of CTX DP at that dose. A further 3 patients may be added to any cohort (to a maximum of 18 of total treated patients) at the discretion of the Data Safety Monitoring Board (DSMB) if required to further clarify the safety profile). A minimum interval of 28 days will be observed between dosing the first and second patient and 7 days between dosing subsequent patients in a given cohort in order to assess the safety and tolerability of CTX DP at that dose.
Post-treatment follow-up: There will be 8 scheduled visits to the clinic for monitoring over the 12 month follow-up period.
End-points: The primary endpoint of the trial is safety, measured by numbers of relevant adverse events, health screening, physical examination (overall and of the treated limb), immunological response, amputation and concomitant medications in the first year after treatment.
Post-trial follow-up: Life-long annual follow-up to record any new cancer via national cancer registry or similar system or by Investigator or family practitioner (as permitted by competent authorities, ethics committees and informed consent).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CTX DP | Experimental | Biological: CTX DPHuman neural stem cell product, single dose administered once only, increasing doses |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed and dated written informed consent obtained from the patient.
- Peripheral arterial occlusive disease due to atherosclerosis (Fontaine stages II, III or IV) of one leg or both defined as
- Fontaine stage II: Intermittent claudication
- Fontaine stage III: Rest pain
- Fontaine stage IV: Ischaemic ulcer or (dry) gangrene
Key exclusion criteria (21 listed)
- Estimated survival of less than 6 months.
- Infection of the involved extremity manifested by fever, purulence, or severe cellulitis or active wet gangrenous tissue wound with exposed tendon or bone.
- Failed ipsilateral revascularisation procedure within 8 weeks prior to enrolment (defined as failure to restore adequate circulation, i.e., the procedure did not achieve an increase in ABPI of 0.15 or more, substantial improvement in Pulse Volume Recording, or clinical improvement).
- Previous amputation of the talus or above in the target limb.
- Planned major amputation within one month of planned date for injection of study medication (CTX DP).
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 |
|---|---|---|
| CTX DPAlso: CTX0E03Single dose treatment consisting of 10 injections (20, 50 or 80 million cells) into the gastrocnemius muscle near to the damaged area | Biological | CTX DP |
Primary outcome
incidence of adverse events
Time frame: 12 months
Monitoring of medical history, general physical examination, physical examination of the ipsilateral leg (inflammation, infection, swelling, tenderness, ulceration, gangrene), temperature, pulse rate and rhythm, ECG, blood pressure, full blood count, liver function tests, serum urea and electrolytes, creatine phosphokinase(muscle isoform), immunological response to CTX, amputation and concomitant medication.
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 31 Jan 2018.
- Derived from this study: PubMed 26752061Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of Content, Stoichiometry and Transfer of miRNA from Human Neural Stem Cell Line Derived Exosomes. PLoS One. 2016 Jan 11;11(1):e0146353. doi: 10.1371/journal.pone.0146353. eCollection 2016.
Related trials for Peripheral Arterial Disease
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
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.
Jill JF Belch, MBChB principal investigator
Ninewells Hospital Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CTX DP in people with Peripheral Arterial Disease, run by ReNeuron Limited at 1 site in United Kingdom.
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 11 inclusion and 21 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 31 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 of adverse events (time frame: 12 months). 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 NCT01916369, which also lists 1 linked publication.
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 31 Jan 2018.