Safety Trial Of CTX Cells In Patients With Lower Limb Ischaemia

NCT01916369 | Completed Phase 1 DMC

• 2 other identifiers: RN09-CP-00012011-005810-13
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Peripheral Arterial Disease

Keywords

Peripheral Arterial Disease; Fontaine Stage II, III or IV; Vascular disease; Cardiovascular diseases; Neural stem cell

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Study Arms (1)

CTX DP

EXPERIMENTAL

Human neural stem cell product, single dose administered once only, increasing doses

Biological: CTX DP

Interventions

CTX DP BIOLOGICAL

Single dose treatment consisting of 10 injections (20, 50 or 80 million cells) into the gastrocnemius muscle near to the damaged area

Also known as: CTX0E03

CTX DP

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ReNeuron Limited: lead

Study Sites (1)

Ninewells Hospital

Dundee, Scotland, DD1 4HN, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26752061 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease; Vascular Diseases; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases

Study Officials

• Jill JF Belch, MBChB

  Ninewells Hospital Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2013
• First Posted: August 5, 2013
• Study Start: April 1, 2014
• Primary Completion: January 16, 2018
• Study Completion: January 16, 2018
• Last Updated: January 31, 2018

Record last verified: 2018-01

Locations

GB (1)