Phase I/II Clinical Trial of HuCNS

ASIA San Antonio 2014 Phase I/II Clinical Trial of HuCNS‐SC Cells in Chronic Thoracic Spinal Cord Injury
Interim analysis
Armin Curt, MD
Principal Investigator
Spinal Cord Injury Center
University of Zürich, Switzerland
Steve Casha, MD
Michael Fehlings, MD
Principal Investigator
University of Calgary
Calgary, Edmonton, Canada
Principal Investigator
University of Toronto
Toronto, Ontario, Canada
Stephen Huhn, MD
VP, CNS Clinical Research and Medical Monitor
StemCells, Inc.
Phase I/II Study Design
• Open‐label, single fixed dose of HuCNS‐SC
– Total intramedullary dose: 20 million cells
Design
– Immunosuppression: 9 month post‐op course
• T2‐T11 thoracic SCI: late sub‐acute to early chronic
– AIS A: 3 to 12 months post‐injury – AIS B: 3 to 24 months post‐injury • Safety and preliminary efficacy endpoints – Adverse Events, Serious Adverse Events, Pain Questionnaire
– Clinical: light touch, pin prick, quantitative sensory testing
– Evoked Potentials: dSSEPs and CHEPs
– Radiological: MR imaging
Transplantation
Pre-op MRI and intra-operative
ultrasound
Surgical HuCNS-SC transplantation
Transplantation
Total dose of 20 million cells
Total volume of 280 μL
4 injections of each 70 μL Lesion
Superior implant
Inferior implant
caudal
rostral
Endpoints
Sensory dermatome testing in SCI
ASIA Scores
Light touch
Pin prick
Quantitative sensory
testing and
electrodiagnostics
Heat Perception Thresholds
CHEPS
Electrical Perception Threshold
dSSEP
CHEPS normal
impaired
EPT normal
3 ‐ 5mA
5‐10mA
Highly impaired
absent
10‐50 mA
EPT absent
Study design and follow‐up
4y Long term follow‐up study
subjects
Overview
0
6
12
1
2
3
4
5
6
7
8
9
10
11
12
1y Ph I/II study
18
24
30
36
42
48
54
60
AIS A (=7)
Zürich (9)
AIS B
(=5)
Calgary (2)
Toronto (1)
level of injury
Overview
ASIA neurological level
T1
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
AIS: 2A & 1B
AIS: 1A & 1B
AIS: 1A & 1B
AIS: 1A & 1B
AIS: A
AIS: A
AIS: B
0
1
2
number of subjects
3
4
Interim report 6 month follow up
0
subjects
interim data
mean: 11.13 months 3
6
0
1
1
2
2
3
3
4
4
5
5
6
6
7
7
8
8
Phase I/IIa study
5
10
15
20
25
Timing of transplant after injury
60
55
age (years)
interim data
Subject age at enrollment
50
45
40
35
mean = 34.7 yrs
30
25
20
15
10
5
0
1
2
3
4
5
subject
6
7
8
AIS A (3 of 5): Stable
Subject 1
Light Touch: Pre‐op to Month 12
Pre‐op
Month 3
Month 6
Month 12
AIS A (2 of 5): Sensory gains
Subject 3
Light Touch: Pre‐op to Month 3
Pre‐op
Day 14
Day28
Month 3
AIS A (2 of 5): Sensory gains
Subject 3
Light Touch: Pre‐op to Month 12
Pre‐op
Month 6
Month 9
Month 12
AIS B (1 of 3): Stable
Subject 4
Light Touch: Pre‐op to Month 12
Pre‐op
Month 3 Month 6
Month 12
AIS B (2 of 3): Sensory gains
Subject 7
Light Touch: Pre‐op to Month 6
Pre‐op
Day28
Month 3
Month 6
Safety
Adverse Events
59 AEs: 9 Zurich subjects to date
60% attributed to underlying SCI or intercurrent illness
17% attributed to surgery or immunosuppression
Most Frequent (>2 events) ‐UTI n=12
‐Decubitus ulcer n=5
‐Headache n=5
4 SAEs:All expected and unrelated to HuCNS‐SC
‐CSF leak (prolonged hospitalisation)
‐Pseudomeningocele (prolonged hospitalization)
‐Constipation (required hospitalization)
‐UTI (required hospitalization)
No post‐transplant deterioration
Safety
Neurological
• No segmental deterioration in AIS A/B
• No segmental or below level deterioration in AIS B
• No ascending deterioration
Functional • No loss of overall functional capacity (ADLs)
• No deterioration of bladder sensation in AIS B
Pain • No change or induction of novel pain syndromes
• No exacerbation of pre‐existing pain
• No unexpected or unknown pain conditions
Spasticity and muscle tone
• No exacerbation of pre‐existing spasticity
• No induction of novel spasticity
PH I/II preliminary efficacy
Efficacy
Sensory changes
• Segmental improvements at/below level of lesion in AIS A
• Below level improvements in AIS B
• Observed sensory changes supported by QST/EP
Timing of changes
• First changes observed 1 ‐ 3 months after transplantation
Summary of Interim Analysis
• Completed enrollment under Swiss, Canadian and US approval
• Minimum 6m data demonstrates safety and feasibility
– surgical route of administration, immunosuppression, technique and cell dose
• Gains in multiple sensory modalities and segments
– 4 out of 8 subjects show signs of segmental sensory improvement • Interim data suggests first signs of a biological and clinical effect with HuCNS‐SC transplantation in spinal cord injury
• Next step
– randomized controlled PH II study in complete and incomplete cervical SCI