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Trial registered on ANZCTR


Registration number
ACTRN12617000684325
Ethics application status
Approved
Date submitted
28/03/2017
Date registered
12/05/2017
Date last updated
7/11/2022
Date data sharing statement initially provided
1/12/2020
Date results information initially provided
1/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Defining a Randomised, Controlled Study of Ortho-ATI (Trademark) vs Corticosteroid Injection for Treatment of Rotator Cuff Tendinopathy and Tear.
Scientific title
Defining a Randomised, Controlled Study of Ortho-ATI (Trademark) vs Corticosteroid Injection for Treatment of Rotator Cuff Tendinopathy and Tear.
Secondary ID [1] 291553 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rotator Cuff Tendinopathy 302647 0
Rotator Cuff Tear 302648 0
Condition category
Condition code
Musculoskeletal 302163 302163 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interventional
Ortho-ATI (Trademark) is a Class 3 Biological autologous tenocyte implantation (ATI) product manufactured in Australia by Orthocell since 2008. Ortho-ATI is intended for homologous and autologous use only. The product comprises of autologous tendon cells taken from healthy patella tendons of patients. These cells are proliferated using an in vitro cell culture technique and reconstituted with patient's own serum for local injection.
Patellar Tendon Biopsy
Autologous tenocytes will be harvested from participants via patellar tendon biopsy under local anaesthetic by an orthopaedic surgeon who has received specific training on ATI biopsy and implantation . A 3 x 1mm strip of tendon will be harvested from the superficial surface of the patella tendon using a 14 gauge biopsy needle. Participants will be advised to avoid over use or excessive repetitive motions for 1-2 days.
Tenocyte Injection
Approximately 4 weeks post-biopsy, up to 2ml of autologous human tenocytes (2-5 x 106 cells/ml) suspended in 10% autologous human serum will be injected using an 18-gauge needle. The injection will be performed under ultrasound guidance into the tendinopathy/tear site at the affected tendon. Participants will be advised to rest for two days and restrict activity to light household/office duties for four weeks.

The Ortho-ATI (trademark) treatment and Celestone comparator are both TGA approved products. and will be administered in a single dose.
Intervention code [1] 297624 0
Treatment: Other
Comparator / control treatment
Participants will receive a single, ultrasound guided injection of 1mL Celestone (Registered Trademark) Chronodose (betamethasone sodium phosphate 3.9mg/betamethasone acetate 3mg) combined with local anaesthetic into the subacromial space.
Control group
Active

Outcomes
Primary outcome [1] 301596 0
Pilot study – no single primary outcome.
Efficacy outcome 1:
MRI evaluation of tendon healing
Timepoint [1] 301596 0
6 and 12 months post treatment.
Primary outcome [2] 333038 0
Efficacy outcome 2:
VAS pain score
Timepoint [2] 333038 0
1, 3, 6, and 12 months post treatment
Primary outcome [3] 333039 0
Efficacy outcome 3:
American Shoulder and Elbow Surgeons Shoulder Assessment (ASES)
Timepoint [3] 333039 0
1, 3, 6, and 12 months post treatment.
Secondary outcome [1] 333612 0
Efficacy outcome 4:
Shoulder function assessed by the Constant-Murley score (CMS)
Timepoint [1] 333612 0
1, 3, 6, and 12 months post treatment.
Secondary outcome [2] 334162 0
Efficacy outcome 5:
Simple Shoulder Test (SST)
Timepoint [2] 334162 0
1, 3, 6, and 12 months post treatment.
Secondary outcome [3] 415588 0
Efficacy outcome 6:
Assessment of Quality of Life (AQoL-6D)
Timepoint [3] 415588 0
1, 3, 6, and 12 months post treatment
Secondary outcome [4] 415589 0
Safety outcome 1:
MRI findings
Timepoint [4] 415589 0
6 and 12 months post treatment.
Secondary outcome [5] 415590 0
Safety outcome 2:
Treatment emergent adverse events

Adverse events will be assessed by clinical examination and participant interview at each study visit, The intensity of events will be graded as either: mild, moderate, severe or extreme, Adverse events may include treatment site reactions such as inflammation or infection,
Timepoint [5] 415590 0
Up to 12 months post treatment.

Eligibility
Key inclusion criteria
Participants must meet all of the following criteria:
-Male or female between 30 and 65 years of age
-Duration of symptoms > 6 months
-Partial thickness, intra-substance supraspinatus tear without communication to the bursal or articular surface, that in the Investigator’s opinion, is of a sufficient size for treatment with Ortho-ATI (trademark), and is verified by MRI
-Previously received one or more corticosteroid injections into the affected joint
-Able to comply with the requirements of the protocol
-Able to give informed consent or has legally acceptable representative who can give informed consent in accordance with ICH/GCP
Minimum age
30 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Corticosteroid or other treatment injection into the affected joint within 3 months of the first study visit.
-Previous shoulder surgery or fracture on the affected side
- Significant pathology of affected shoulder, that could, in the opinion of the Investigator, potentially compromise the outcome of treatment
- Bilateral shoulder pathology
Active infection or systemic pathology including inflammatory joint disease, HIV, uncontrolled or poorly controlled diabetes, hepatitis or neoplastic disorders
Neuromuscular disease of the affected arm
-Metabolic bone disorder which could impair bone or soft tissue function
-Professional athlete
-Workers compensation or other compensation case
-Known hypersensitivity to the study treatment or its excipients or known relevant medication allergy
-Contraindicated to MRI
-Female participant who is pregnant or lactating
-Known substance abuse
-Participation in another study with an investigational product within 3 months of the first planned study visit
-Concurrent medical condition which precludes the administration of study treatment or comparator
-Other clinically significant disease (including psychological disorders), medical condition or other factor that would, in the opinion of the Investigator, compromise the safety of the participant or the outcome of the study

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)
Investigators will receive individual sealed opaque envelopes containing the treatment allocation for each participant. Patients will be randomised after informed consent has been obtained and eligibility to participate in the study has been confirmed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
To minimise bias, participants will be randomly assigned in a 2:1 ratio to either Ortho-ATI (Trademark) (ARM A) or corticosteroid injection (ARM B). A computer-generated permuted block strategy will be used to generate the master randomisation list, which will be held securely by the sponsor. Block size will not be disclosed by the statistician who prepares the list.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Demographic data will be displayed and summary statistics used to describe the study population.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2017
Actual
25/07/2017
Date of last participant enrolment
Anticipated
31/12/2018
Actual
23/06/2020
Date of last data collection
Anticipated
30/07/2021
Actual
18/08/2021
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 7737 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 15663 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 296041 0
Commercial sector/Industry
Name [1] 296041 0
Orthocell Ltd
Country [1] 296041 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Orthocell Ltd
Address
Building 191
Murdoch University
South Street
Murdoch WA 6150
Country
Australia
Secondary sponsor category [1] 294933 0
None
Name [1] 294933 0
Address [1] 294933 0
Country [1] 294933 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297300 0
St John of God Health Care HREC
Ethics committee address [1] 297300 0
12 Salvado Road
Subiaco
WA 6008
Ethics committee country [1] 297300 0
Australia
Date submitted for ethics approval [1] 297300 0
07/03/2017
Approval date [1] 297300 0
12/04/2017
Ethics approval number [1] 297300 0

Summary
Brief summary
The objectives of treatment of symptomatic rotator cuff disease are to relieve pain and restore movement and function of the shoulder. Conservative treatments include rest, NSAIDs, glucocorticoid injections and physical therapy. While specific exercise therapy may be beneficial, most of these treatments often only temporarily relieve the patients’ symptoms, and do not address the underlying tendon pathology.
A combination of an increased understanding of pathological processes involved in tendinopathy as well as the success of other autologous therapies for tissue repair has highlighted the potential for tendon repair by delivery of tenocytes to the site of injury. Tendon-derived cells, including tendon progenitor cells (TPCs), possess the potential for tendon regeneration as they have the capacity for collagen synthesis, proliferate rapidly and are self-renewable.
The efficacy of tenocyte implantation for stimulation of tendon repair has been verified in a number of in vitro and animal studies. Animal studies have revealed that implantation of in vitro expanded autologous tenocytes improved the tendon structure and facilitated the healing process in both an acute tendon tear model and a chronic degenerative tendon disease model . Based on these studies, it was proposed that restoration of functional cells capable of synthesizing extracellular matrix and repairing the damaged tissue within the tendon may be an effective therapeutic strategy for tendon repair. This method is the basis of the Ortho-ATI (Trademark) tenocyte therapy product developed by Orthocell.
Imaging studies of rotator cuff tear indicate that injury to the supraspinatus tendon is most likely to be the cause of rotator cuff disease. The majority of supraspinatus tendon tears occur within a zone close to the tendon insertion. This is most likely due to lack of vascularity within that portion of tendon, and/or increased tensile loading. Furthermore, concealed lesions within the substance of the tendon (interstitial or intrasubstance tears) account for approximately one third of rotator cuff tears detected at the tendon insertion. These lesions present an unmet area of clinical need, as they are not suitable for surgical correction, should non-surgical treatments fail.
Ortho-ATI (Trademark) is a minimally-invasive treatment which, unlike other conservative treatments, directly addresses the underlying pathology of rotator cuff tendinopathy and tear.
This randomised, controlled study has been designed to investigate the feasibility of Ortho-ATI (Trademark) as an alternative treatment for patients with partial, intrasubstance rotator cuff tear and tendinopathy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73630 0
Prof Allan Wang
Address 73630 0
c/o St John of God Hospital Medical Clinic
25 McCourt Street
Subiaco WA 6008
Country 73630 0
Australia
Phone 73630 0
+61 8 9366 1577
Fax 73630 0
+61 8 9311 4105
Email 73630 0
AllanWang@aapt.net.au
Contact person for public queries
Name 73631 0
Prof Allan Wang
Address 73631 0
c/o St John of God Hospital Medical Clinic
25 McCourt Street
Subiaco WA 6008
Country 73631 0
Australia
Phone 73631 0
+ 61 8 9366 1577
Fax 73631 0
+61 8 9311 4105
Email 73631 0
AllanWang@aapt.net.au
Contact person for scientific queries
Name 73632 0
Dr Clair Lee
Address 73632 0
Clinical Research Manager
Orthocell Ltd
Building 191 Murdoch University
South Street
Murdoch
WA 6150
Country 73632 0
Australia
Phone 73632 0
+61 8 9360 2888
Fax 73632 0
+61 8 9360 2899
Email 73632 0
clair.lee@orthocell.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified line listings.
When will data be available (start and end dates)?
After publication, no end date.
Available to whom?
Researchers with a scientifically and methodologically sound research proposal which has been approved by a Human Research Ethics Committee, as assessed on a case-by-case basis.
Available for what types of analyses?
Meta-analysis.
How or where can data be obtained?
Subject to approval from the Principal Investigators and Sponsor.

Email: luke.hanrahan@orthocell.com.au


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.