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Trial registered on ANZCTR


Registration number
ACTRN12609001049268
Ethics application status
Approved
Date submitted
21/05/2009
Date registered
8/12/2009
Date last updated
20/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1b/2a, Randomised, Single-Blinded, Controlled Study Evaluating Safety and Preliminary Efficacy of NeoFuse(TM) when combined with MasterGraft (TM) matrix in Patients Undergoing Multi-Level Anterior Cervical Discectomy and Fusion with Anterior Cervical Plate Fixation.
Scientific title
A Phase 1b/2a, Randomized, Double-Blinded, Controlled Study Evaluating Safety and Preliminary Efficacy of NeoFuse (TradeMark) when Combined with MasterGraft Granules in Subjects Undergoing Multi-Level Anterior Cervical Discectomy.
Secondary ID [1] 883 0
Nil
Universal Trial Number (UTN)
Trial acronym
ACDF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anterior cervical discectomy with interbody cage and fusion 4829 0
Condition category
Condition code
Neurological 237171 237171 0 0
Other neurological disorders
Surgery 252471 252471 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Surgically/direct sterile application of 10 Million Mesenchymal Precursor Cells and Mastergraft Matrix made of medical grade combination of purified collagen and biphasic calcium phosphate ceramic. The collagen is highly purified (>95%) Type I bioresorbable lyophilized collagen. The biphasic ceramic portion of MasterGraft(TM) Matrix is provided in a 15% hydroxyapatite and 85% b-tricalcium phosphate formulation. The cells and matrix will be prepared/combined and implanted at each involved cervical level for a total dose of 20 or 30 million cells or mastergraft granules only per involved cervical level. The duration of an anterior cervical discectomy and fusion procedure is 2-3 hours.
Intervention code [1] 4607 0
Treatment: Surgery
Comparator / control treatment
MasterGraft Granules - granules are mixed with venous blood and placed into a cervical cage.
Control group
Active

Outcomes
Primary outcome [1] 237989 0
To determine the safety and feasibility of interbody fusion with and exploratory dose of NeoFuse (allogeneic mesenchymal precursor cells [MPCs]), combined with Mastergraft Matrix as a carrier and radiolucent cervical cage for multi-level anterior cervical discectomy and fusion (ACDF) with anterior cervical plate fixation through 12 months follow-up of adverse events.
Timepoint [1] 237989 0
Each subject will be followed for 2 years after surgery and will have assessments at screening, during surgery, post operatively at 1 to 3 days and 30 days, and again at 3, 6, 12 and 24 months after surgery.
Secondary outcome [1] 242114 0
To evaluate the overall fusion success with NeoFuse plus Mastergraft Matrix compared to control (Mastergraft Granules) using computed tomography (CT) scans of the involved cervical spine levels through 12 months.
Timepoint [1] 242114 0
3, 6, 12 months post surgery
Secondary outcome [2] 242115 0
To evaluate the overall fusion success with NeoFuse plus Mastergraft Matrix compared to control (Mastergraft Granules) using flexion/extension, anteroposterior (AP), and lateral radiographs through 12 months. Radiographic fusion success will be determined by measuring the degrees of angular motion and bridging bone between the involved vertebral endplates.
Timepoint [2] 242115 0
1, 3, 6, 12 months post surgery
Secondary outcome [3] 242116 0
To evaluate the change from baseline in the Neck Disability Index (NDI)
Timepoint [3] 242116 0
1, 3, 6, 12 and 24 months post surgery
Secondary outcome [4] 242117 0
To evaluate the change from baseline in the Medical Outcome Study Short Form (SF-36)
Timepoint [4] 242117 0
1, 3, 6, 12 and 24 months post surgery
Secondary outcome [5] 242118 0
To evaluate the change from baseline in pain level using the visual analog scale (VAS) for neck and arms
Timepoint [5] 242118 0
1, 3, 6, 12 and 24 months post surgery
Secondary outcome [6] 242119 0
To evaluate the change from baseline in subjects psychological well being using Zung Depression Scale
Timepoint [6] 242119 0
1, 3, 6, 12 and 24 months post surgery
Secondary outcome [7] 265637 0
To evaluate the change from baseline in participants Work Productivity Activity Index (WPAI)
Timepoint [7] 265637 0
1, 3, 6, 12 and 24 months post surgery.

Eligibility
Key inclusion criteria
1. Male or females between 18 and 70 years of age, inclusive
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from participating in the study if they meet any of the following exclusion criteria:
1. Female participants who are pregnant or breast feeding or women planning to become pregnant during the first year (12 months) following surgery
2. Has at the time of surgery a systemic or local infection at the site of proposed surgery.
3. Has or is undergoing revision of a prior fusion surgery at any involved level.
4. Requires ACDF at only one cervical interbody level or more than 3 adjacent cervical interbody levels.
5. Requires ACDF without the use of an anterior cervical plating system.
6. Has an acute fracture of the cervical spine at the time of enrollment in the study
7. Has a history of epidural steroid injections within 1 week prior to study treatment
8. Has received chronic (more than 7 consecutive days) treatment with systemic corticosteroids at a dose equivalent to prednisone = 10 mg/day within 14 days prior to study procedure and/or is unwilling to refrain from systemic use of corticosteroids for the first 6 months following surgery
9. Has received systemic or local injections into the index and/or adjacent vertebral levels nonsteroidal anti-inflammatory drugs (NSAIDS) within 48 hours prior to study procedure and/or is unwilling to refrain from such treatments with NSAIDS for the first 6 months following surgery.
10. Has a known history of hypersensitivity or anaphylactic reaction to murine or bovine products, dimethyl sulfoxide (DMSO), or calcium-phosphate (CaPO4)-based synthetic bone graft substitutes.
11. Has a current or prior history within the last 3 years of neoplasm (excluding basal cell carcinoma) and/or any active neoplasm within the last 24 months prior to screening.
12. Have osteoporosis as defined by a DEXA T score of = -3.0 or a history of fragility fractures or other significant bone disease contraindicating the use of spinal instrumentation
13. Has systemic immune disease requiring chronic steroid therapy.
14. Plan or require the use of bone growth stimulator devices (implantable or not) as an adjunct to surgery or during the trial 24-months duration.

15. Plan or require the use of osteobiologic bone growth stimulator devices, e.g., bone morphogenetic proteins (BMPs) at fusion surgery or during this trial’s 24-months duration.
16. Has a documented medical history or radiographic evidence of a metabolic bone disease or other condition which would negatively impact the bone healing process (e.g. history of Paget’s disease, osteomalacia, or other osteodystrophy).
17. Has a positive screen for human immunodeficiency virus (HIV) antibodies.
18. Has had treatment with any investigational therapy or device within 6 months of study surgery and/or plans to participate in any other allogeneic stem cell/progenitor cell therapy trial during the 2-year follow-up period.
19. Has been a recipient of prior stem cell/progenitor cell therapy for spinal fusion surgery.
20. Has a medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., histories of transient ischemic attack (TIA), stroke, uncontrolled diabetes, or liver disease).
21. Has 20% or greater anti-human leukocyte antigen (HLA) antibody titer and/or has antibody specificities to donor HLA antigens.
22. Is transient or has been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program.
23. Currently has Syphilis
24. Currently incarcerated (prisoners).
25. Unable to complete follow-up according to the protocol.
26. Have a mental illness that could prevent completion of the study or protocol questionnaires.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation envelopes prepared by a biostatistitian with assigned/allocaed randomisation numbers. Once the patient is found to be eligible and surgery date confirmed, an unblided study delegate will select an envelope and assign the randomisation number and treatment to the patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible subjects will be randomized to receive one of two treatments at each fusion level: NeoFuse TradeMark (TM) 10 million allogeneic MPCs per involved interbody space combined with MasterGraft (TM) Granules or MasterGraft(TM) Granules alone (control). The treatment will be administered as a direct sterile application to the involved level(s), for a total dose per study subject of either 20 or 30 million MPCs if study subject randomised to 10 million MPCs. Randomisation numbers will be assigned as per the randomisation envelopes preprapared by the biostatitician. The biostatistitian will use a simple randomisation table to create the code placed in the envelopes. This table will be generated using computer software (i.e., computerised sequence generation). The envelopes will be supplied to the cell storage facility and the unblinded persnnel will select the next envelope in sequence that will indicate the randomisation number and dose for that patient.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Eligible subjects will be randomized to receive one of two treatments at each fusion level: NeoFuse TradeMark (TM) 10 million allogeneic MPCs per involved interbody space combined with MasterGraft (TM) Granules or MasterGraft(TM) Granules alone (control). The treatment will be administered as a direct sterile application to the involved level(s), for a total dose per study subject of either 20 or 30 million MPCs if study subject randomised to 10 million MPCs.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4990 0
Commercial sector/Industry
Name [1] 4990 0
Mesoblast Ltd
Address [1] 4990 0
Level 39
55 Collins Street
Melbourne
Victoria 3000
Country [1] 4990 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Mesoblast Ltd
Address
Level 39
55 Collins Street
Melbourne
Victoria 3000
Country
Australia
Secondary sponsor category [1] 4513 0
None
Name [1] 4513 0
Address [1] 4513 0
Country [1] 4513 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 7092 0
Epworth Healthcare
Ethics committee address [1] 7092 0
Level 5
Leigh Place
Epworth Hospital
Richmond Victoria 3121
Ethics committee country [1] 7092 0
Australia
Date submitted for ethics approval [1] 7092 0
18/12/2008
Approval date [1] 7092 0
04/02/2009
Ethics approval number [1] 7092 0
43509
Ethics committee name [2] 258241 0
Melbourne Health Ethics Committee
Ethics committee address [2] 258241 0
Royal Melbourne Hospital
Parkville Victoria 3050
Ethics committee country [2] 258241 0
Australia
Date submitted for ethics approval [2] 258241 0
Approval date [2] 258241 0
18/11/2009
Ethics approval number [2] 258241 0
2009.226
Ethics committee name [3] 259698 0
Southern Health Research Directorate
Ethics committee address [3] 259698 0
Level 4, Main Block,
Monash Medical Centre
246 Clayton Road
CLAYTON VIC 3168
Ethics committee country [3] 259698 0
Australia
Date submitted for ethics approval [3] 259698 0
Approval date [3] 259698 0
22/06/2010
Ethics approval number [3] 259698 0
10085B

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29628 0
Address 29628 0
Country 29628 0
Phone 29628 0
Fax 29628 0
Email 29628 0
Contact person for public queries
Name 12875 0
Toula Papadimitrakis
Address 12875 0
Level 39
55 Collins Street
Melbourne 3000
Victoria
Country 12875 0
Australia
Phone 12875 0
+61 3 9639 6036
Fax 12875 0
+ 61 3 9639 6030
Email 12875 0
toula@mesoblast.com
Contact person for scientific queries
Name 3803 0
Toula Papadimitrakis
Address 3803 0
Level 39
55 Collins Street
Melbourne 3000
Victoria
Country 3803 0
Australia
Phone 3803 0
+61 3 9639 6036
Fax 3803 0
+61 3 9639 6030
Email 3803 0
toula@mesoblast.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary