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Trial registered on ANZCTR


Registration number
ACTRN12616001259437
Ethics application status
Approved
Date submitted
26/08/2016
Date registered
8/09/2016
Date last updated
16/10/2019
Date data sharing statement initially provided
16/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study using non-expanded stem cells for the treatment of early osteoarthritis of the knee (focal chondral defects) in comparison to standard conservative management.
Scientific title
A proof-of-concept study on the safety and efficacy of autologous stromal vascular fraction and platelet rich plasma for the treatment of symptomatic focal chondral lesions of the knee in comparison to accepted conservative management.
Secondary ID [1] 290031 0
Nil
Universal Trial Number (UTN)
U1111-1186-4118
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Focal chondral lesions of the knee 300068 0
Condition category
Condition code
Musculoskeletal 299952 299952 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will look to assess the safety and response of focal chondral lesions of the knee to injection protocols of stromal vascular fraction (SVF) and platelet rich plasma (PRP) in comparison to accepted conservative mangement. Thirty two participants will be enrolled in the study and randomly separated into 2 study groups.

Group 1: [SVF (IA) + PRP (IA)] at Day 0 + PRP (IA) at Days 7, 14 & 28
Group 2: accepted conservative management including: simple analgesics, weight loss education, regular exercises, biomechanical adjustment

Autologous non-expanded SVF from adipose (fat) will be used due to the ease of harvest (liposuction) and safety. On average 100 million cells are injected into the joint. Adipose tissue is removed by lipo-aspiration (about 60 minutes). The fat is processed on-site to isolate the cells (this process takes up to 40 mins). The suspension of stromal stem cells is injected into the knee joint under ultrasound guidance. The PRP (3ml) process involves separating out platelets with plasma from a small amount of blood taken, and takes about 15 mins.

The harvesting of adipose and the PRP processing will be performed on the same day as the injection of SVF and PRP, respectively.
Intervention code [1] 295752 0
Treatment: Other
Comparator / control treatment
Comparator treatment: accepted conservative management including: simple analgesics, weight loss education, regular exercises, biomechanical adjustment. Conservative management will be by face to face meeting with the doctor on Days 0, 180 and 365.
Control group
Active

Outcomes
Primary outcome [1] 299441 0
Safety and tolerability of autologous stromal vascular fraction (SVF) and platelet rich plasma (PRP) for the treatment of focal chondral lesions of the knee. Adverse Events will be graded by the Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) and coded according to MedDRA terminology. Loco regional Adverse Events will be monitored (e.g. knee swelling, infection). Systemic Adverse Events will monitored by. laboratory parameters including [blood tests: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), and pregnancy test for female patients], and vital signs (temperature, heart rate, blood pressure, respiration rate and weight),
Timepoint [1] 299441 0
Assessed at Days 0, 7, 14, 28, 56, 180, 365.
Secondary outcome [1] 327152 0
The KOOS (Knee Injury and Osteoarthritis Outcome Score) questionnaire will assess the patient’s opinion about their knee and associated problems.
Timepoint [1] 327152 0
Assessed at Day 0,28, 56, 90, 180,365
Secondary outcome [2] 327153 0
The AQoL (Australian Quality of Life) questionaire is a health-related multi-attribute utility quality of life instrument.
Timepoint [2] 327153 0
Assessed at Day 0,28, 56, 90, 180,365
Secondary outcome [3] 327154 0
The SF-36 (Short Form Health) survey is used as a patient-reported survey of patient health.
Timepoint [3] 327154 0
Assessed at Day 0,28, 56, 90, 180,365
Secondary outcome [4] 327155 0
Rescue medication consumption (e.g. analgesics). This outcome is assessed by self reported changes in the daily use and dosage of an individuals medication, along with data linkage to patients medical records
Timepoint [4] 327155 0
Assessed at Day 0,28, 56, 90, 180,365
Secondary outcome [5] 327156 0
MRI findings (cartilage mapping) will be used to assess disease modification. Cartilage mapping of the knee will indicate if a patient has improved cartilage volume or not.
Timepoint [5] 327156 0
Assessed at Day 0, 180,365

Eligibility
Key inclusion criteria
1. Focal chondral lesions of the knee (as evidenced by MRI scan) with symptomatic pain and less than or equal to 6 cm2 in size.
2. Greater than 6 months knee pain with the index side (left or right) predominately on one side
3. A KOOS pain score greater than or equal to 65
4. Adequate blood chemistry and hematopoietic, renal, cardiovascular, respiratory, immunological function
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects who have received investigational agents within 4 weeks (or 5 half-lives) of SVF/placebo infusion.
2. Presence of clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological (viral hepatitis, or cirrhosis), endocrine, or central nervous system disorders.
3. Subjects who have had active neoplastic disease in the previous 3 years.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The study safety results will be analysed by descriptive statistics, as rigorous inferential statistics will not be feasible due to the small treatment group sample size. The primary analysis for safety will report all subject adverse events.

All efficacy analyses will be performed using the Intention to Treat (ITT) population. The chosen sample size of 32 patients allows for 16 patients per treatment cohort which is sufficient to detect a difference between the comparison group and SVF (with PRP) group in the mean percentage change over time in KOOS scores of 20% with a standard deviation of 10% or difference of 10% with a much larger standard deviation of 20%.

The endpoints for the MRI will be to assess disease modification following cartilage mapping of the MRI scans. The reviewer will indicate whether a participant has improved cartilage volume and the degree or not, or that degeneration has slowed in comparison to the placebo control. No formal statistical tests will be undertaken.


Recruitment
Recruitment status
Not yet 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)
NSW
Recruitment postcode(s) [1] 14149 0
2298 - Georgetown

Funding & Sponsors
Funding source category [1] 294397 0
Commercial sector/Industry
Name [1] 294397 0
Cell-Innovations Pty Ltd
Address [1] 294397 0
PO Box 7342
Warringah Mall
Brookvale NSW 2100
Country [1] 294397 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Cell-Innovations Pty Ltd
Address
PO Box 7342
Warringah Mall
Brookvale NSW 2100
Country
Australia
Secondary sponsor category [1] 293245 0
None
Name [1] 293245 0
Address [1] 293245 0
Country [1] 293245 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295820 0
Northern Sydney Local Health District
Ethics committee address [1] 295820 0
Kolling Bld, level 13
Royal North Shore Hospital
St leonards NSW 2065
Ethics committee country [1] 295820 0
Australia
Date submitted for ethics approval [1] 295820 0
14/12/2015
Approval date [1] 295820 0
12/07/2016
Ethics approval number [1] 295820 0
HREC/15/HAWKE/484

Summary
Brief summary
The primary objective of this study is to determine the safety and tolerability of autologous stromal vascular fraction (SVF) and PRP in comparison to standard conservative management of patients with focal chondral lesions of the knee.

Secondary objectives are intended to measure differences between standard treatment and SVF based therapies including improvement of pain and mobility, quality of life and MRI to assess disease modifying activity.
Trial website
www.cell-innovations.com.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68602 0
Dr David Mathers
Address 68602 0
Hunter Regenerative Medicine
71 Georgetown Rd
Georgetown NSW 2298
Country 68602 0
Australia
Phone 68602 0
+61 (02) 49601933
Fax 68602 0
Email 68602 0
davidmathers@tpg.com.au
Contact person for public queries
Name 68603 0
Dr Wayne Thomas
Address 68603 0
Cell-Innovations
PO Box 7342
WARRINGAH NSW 2100
Country 68603 0
Australia
Phone 68603 0
+61 1300 738 025
Fax 68603 0
Email 68603 0
trials@cell-innovations.com.au
Contact person for scientific queries
Name 68604 0
Dr Wayne Thomas
Address 68604 0
Cell-Innovations
PO Box 7342
WARRINGAH NSW 2100
Country 68604 0
Australia
Phone 68604 0
+61 1300 738 025
Fax 68604 0
Email 68604 0
wthomas@cell-innovations.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?
Individual participant data that underlie the results reported in an article after deidentification (text, tables, figures, and appendices)
When will data be available (start and end dates)?
beginning 3 months and ending 36 months following an articles publication
Available to whom?
Investigators whose proposed use of the data has been approved by an independent review committee (learned intermediary) identified for this purpose
Available for what types of analyses?
For individual participant data meta-analysis
How or where can data be obtained?
Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link to be provided).
What supporting documents are/will be available?
No other documents available
Summary results
No Results