ReNeuron’s clinical trials
PISCES Clinical trial in stroke patients
The PISCES study (Pilot Investigation of Stem Cells in Stroke) is the world’s first fully regulated clinical trial of a neural stem cell therapy for disabled stroke patients. Stroke is the third largest cause of death and the single largest cause of adult disability in the developed world.
The PISCES Phase I clinical trial is currently in long-term follow-up and has been conducted in Scotland at the Institute of Neurological Sciences, Southern General Hospital, Greater Glasgow and Clyde NHS Board. In this single administration dose escalation safety study, ReNeuron’s ReN001 stem cell therapy was administered in ascending doses to a total of 11 stroke patients who have been left disabled by an ischaemic stroke, the most common form of the condition. The Principal Investigator for the trial is Professor Keith Muir, SINAPSE Professor of Clinical Imaging, Division of Clinical Neurosciences at the University of Glasgow. The aim of the clinical trial is to evaluate the safety of the implantation technique and to establish the side effect profile associated with the implantation of ReN001 stem cells in patients who have suffered an ischaemic stroke.
Patients in the Phase I trial are followed up over a two year period. Ongoing monitoring of the patients will also continue in the longer term following the two year end-point. Although the primary endpoints of the clinical trial relate to the safety and tolerability of the ReN001 treatment, a number of clinical assessments of the patients in the trial are being made to evaluate changes in both motor and cognitive function over time.
In May 2014, long term follow up data to 12 months in all 11 patients treated in the PISCES study were presented by the clinical team from Glasgow’s Southern General Hospital at the 23rd European Stroke Conference in Nice, France.
There were no cell-related or immunological adverse events reported in any of the patients treated in the study. Adverse events were related only to the implantation procedure or underlying co-morbidities. Sustained reductions in neurological impairment and spasticity were observed in most patients compared to their stable pre-treatment baseline performance, reflected in the summary evaluation scores below (n=11 patients):
• National Institutes of Health Stroke Scale (measure of neurological deficit):
Trial inclusion criteria require a score of 6 or more, representing stable moderate to severe disability (total of 2 or more for motor arm and leg scores):
o Median pre-treatment score = 7
o Post-treatment scores improved by median 2 points at 3 months and 3 points at 12 months
• Barthel Index (measure of independence in performing activities of daily living, rated 0- 20):
o Median pre-treatment score = 12
o Post-treatment scores improved by median 1 point at 3 months and 3 points at 12 months
• Summated Ashworth Score (aggregated measure of spasticity in affected limbs, rated 0-40 arm, 0-25 leg):
o Mean pre-treatment aggregate score = 29
o Post-treatment scores improved by mean 5 points at 3 months and 7 points at 12 months
• Modified Rankin Score (overall measure of disability and handicap, rated 0-6):
o Median pre-treatment score = 3
o Score improved by 1 grade in n=4/11 patients at 12 months, with n=7/11 patients unchanged
• EuroQOL score (quality of life outcome measure, rated 0-100):
o Median pre-treatment score = 45
o Post-treatment scores improved by median 18 points at 12 months.
Preliminary functional MRI data in 7 of the treated patients at resting state show, at a group level, evidence of increased short-term connectivity between the cell-implanted region of the brain (the putamen) and the other deep brain regions that are concerned with sensory motor control, although relevance to functional outcomes in the patients requires further evaluation.
A Phase II study has now commenced in up to 10 UK centres. The study will involve the treatment of up to 41 patients between 8 and 12 weeks after their stroke. Patients will be monitored on a number of validated stroke efficacy measures up to six months post-treatment. The treatment window in the Phase II clinical trial is regarded as optimal in terms of the potential efficacy of the ReN001 therapy and differs from the treatment window in the Phase I clinical trial where patients were treated at least 6 months after their stroke.
The Phase II study has been adopted by the NHS National Institute for Health Research Stroke Research Network (SRN), enabling the Company to work closely with the SRN to optimise performance against defined targets regarding site set-up, patient recruitment and monitoring activities across the various sites participating in the study. The study is expected to read out by the end of 2015.
Observational study in stroke
Alongside the Phase II stroke study with ReN001, we have commenced a non-interventional, observational study in stroke patients, initially at a selection of the clinical sites that will participate in the Phase II study. The observational study will allow for the pre-screening of potentially eligible patients for the Phase II clinical trial at the sites concerned, enabling such patients to be identified in good time while still in acute stroke care at the hospital. The observational study will also monitor eligible stroke patients who do not ultimately participate in the Phase II study with ReN001 on the same end-point measures, thus enabling a broad and valuable clinical data set to be built around the stroke patient sub-population targeted with the ReN001 therapy.
Phase I clinical trial in critical limb ischaemia
We have commenced a Phase I clinical trial with our ReN009 investigational therapy for critical limb ischaemia (CLI). This major disease is common in patients with diabetes and can lead to amputation of the affected limb. Our ReN009 therapy is a cell-based treatment for CLI patients, which, in pre-clinical studies, has shown the potential to restore sufficient blood flow in the affected lower limb to avoid amputation, and therefore the severe health consequences that typically result from such a procedure. The trial is being undertaken through NHS Tayside at Ninewells Hospital and Medical School, Dundee, Scotland. In this dose escalation safety study, the ReN009 cells will be administered via straightforward intramuscular injection into the affected lower limb of nine patients with peripheral arterial disease (CLI is the end-stage of this disease). Patients will be monitored for up to 12 months to assess the safety and tolerability of the treatment.