Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000622808
Ethics application status
Approved
Date submitted
26/01/2021
Date registered
24/05/2021
Date last updated
10/04/2024
Date data sharing statement initially provided
24/05/2021
Date results information initially provided
24/05/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
An observational long term follow-up safety and efficacy study of the MAG200 randomised controlled study to evaluate allogeneic adipose-derived mesenchymal stem cells in the treatment of symptomatic osteoarthritis of the knee.
Scientific title
A observational long term Phase I/II study of the MAG200 randomised, double blind, placebo-controlled, single ascending dose study to evaluate the efficacy and longer-term safety and tolerability of allogeneic adipose-derived mesenchymal stem cells in the treatment of symptomatic knee osteoarthritis.
Secondary ID [1] 303265 0
Magellan Biologicals Pty Ltd, MSC-OAK-002
Universal Trial Number (UTN)
Trial acronym
Linked study record
This record is an observational long-term follow-up study of the ACTRN12617001095358 study.

Health condition
Health condition(s) or problem(s) studied:
osteoarthritis 320451 0
Condition category
Condition code
Musculoskeletal 318343 318343 0 0
Osteoarthritis

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
12
Target follow-up type
Months
Description of intervention(s) / exposure
This observational trial runs in parallel to the interventional trial MSC-OAK-001 (ACTRN12617001095358). It is designed to assess the efficacy and longer-term safety of investigational product MAG200. Mag200 is a preparation of allogeneic human adipose-derived mesenchymal stem cells (MSCs) in sterile, clinical grade injectable isotonic solution. Up to 40 subjects with a documented diagnosis of osteoarthritis of the knee, confirmed by X-ray and MRI during Screening, and who have met the eligibility criteria for the parallel interventional trial MSC-OAK-001 will be offered the opportunity to enrol in this observational study. Following provision of written informed consent and confirmation of eligibility, eligible subjects will commence both protocols on the same day. Subjects enrolled in Protocol MSC-OAK-001 will be on-study for Months 0-3. Subjects enrolled in Protocol MSC-OAK-002 will be on-study for Months 0-12. Participants will complete questionnaire based follow-up at 0, 1, 3, 6, 9 and 12 months. Participants will undergo radiological follow-up including Xray and MRI at 12 months. Questionnaires will be completed using online software and independently by the participants. Questionnaires are expected to take up to 20minutes. Radiological imaging at 12 months is expected to take up to 1hour.

Participants in this trial will be the same participants enrolled in the interventional trial ACTRN12617001095358.
Intervention code [1] 319565 0
Not applicable
Comparator / control treatment
Placebo treatment will be administered to participants enrolled in the interventional study ACTRN12617001095358 and the same participants will be enrolled and followed up as the placebo cohort in this observational study.
Control group
Placebo

Outcomes
Primary outcome [1] 337949 0
Responder Analysis as determine by Pain (as assessed by numeric rating scale [NRS]) and Function (as assessed by Knee Injury Osteoarthritis Outcome Score Subscale - Function in Daily living [KOOS ADL]).
Timepoint [1] 337949 0
Primary outcome [2] 337950 0
Responder Analysis as determine by Pain (as assessed by numeric rating scale [NRS]) and Function (as assessed by Knee Injury Osteoarthritis Outcome Score Subscale - Function in Daily living [KOOS ADL]).
Timepoint [2] 337950 0
12 months post Day 0 (First day of treatment)
Secondary outcome [1] 391008 0
Patient report outcome measures (PROM) including
- Patient Global Impression of Change
Timepoint [1] 391008 0
12 months post Day 0 (First day of treatment)
Secondary outcome [2] 391009 0
Pain as assessed by numeric rating scale (NRS)
Timepoint [2] 391009 0
0, 1, 3, 6, 9 months post Day 0 (First day of treatment)
Secondary outcome [3] 391010 0
Knee Injury and Osteoarthritis Outcome Score Subscales - Pain, Symptoms, Function in Daily Living, Function in Sport and Recreation and Quality of Life,
Timepoint [3] 391010 0
0, 1, 3, 6, 9, 12 months post Day 0 (First day of treatment)
Secondary outcome [4] 391011 0
Structural outcome assessed by MRI cartilage volume mapping
Timepoint [4] 391011 0
12 months post Day 0 (First day of treatment)
Secondary outcome [5] 391012 0
Safety and tolerability of MAG200. It will be assessed by monitoring adverse events, conducting physical examination, vital signs, ECG, clinical laboratory data and concomitant medication usage.
Timepoint [5] 391012 0
Physical exam and vital signs will be assessed at Days 0, 7, 14, 28, month 3. 6, 9 and 12 post Day 0 (First day of treatment)
ECG will be performed at Days 0, 28 and month 3.
Clinical laboratory testing will be assessed at Days 0, 7, 28 and month 3, 6, 9 and 12 (post Day 0 (First day of treatment))
Adverse events and concomitant medication use will be captured and assessed from Day 0 to month 12.
Secondary outcome [6] 392697 0
Structural outcome assessed by MRI T2mapping
Timepoint [6] 392697 0
12 months post Day 0 (First day of treatment)
Secondary outcome [7] 395125 0
Subject satisfaction with treatment
- assessed using a study specific questionnaire.
Timepoint [7] 395125 0
12 months post Day 0 (First day of treatment)

Eligibility
Key inclusion criteria
i) Body mass index BMI must be 'greater than or equal' to 19.0 kg/m2 and 'less than or equal to' 35.0 kg/m2;
ii) A documented diagnosis of osteoarthritis (Grade 2 or Grade 3) of the study knee
iii) Participants enrolled in the interventional MAG200 study (ACTRN12617001095358)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) MRI-confirmed displaced meniscal tear, ligament deficiency or generalised Grade 4 chondral loss in the study knee.
ii) History of or suspected infective or inflammatory joint disorders.
iii) Joint surgery within 3 years prior to study start.
iv) Females who are pregnant or planning a pregnancy during the following 12 months.
v) Any contraindication to intra-articular injection.
vi) Any contraindication to an X-ray or MRI of the study knee.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
All patients will be included in the ITT population. All analyses use the ITT population.
Analysis of primary endpoint -
The primary endpoint of overall responder will be analysed using a stratified (by timepoint) Cochrane Mantel Haenzel approach for each dose where a 2x2 table (responder x treatment) will be obtained for each timepoint from which the number (and percentage) of responders in each treatment group at each timepoint will be obtained. In addition estimates of the ‘risk difference’ (the difference in percentage of responders calculated as percentage on active – percentage on placebo) and a relative risk (percentage responders on active/percentage responders on placebo) will be obtained. An exact chi-square test will be performed at each timepoint to test whether the percentage of responders was different between active and placebo. In addition the overall, common relative risk (with 95% confidence limits) will be obtained.
Secondary efficacy endpoints and analyses -
To assess the effect of active treatment compared with placebo a mixed model will be fitted with change in NRS/KOOSx as the outcome variable and dose and timepoint (and the dosextimepoint interaction) as factors.
The results for the satisfaction scales and PGIC will be summarised by timepoint and dose.

For cartilage volumes assessment by MRI a general linear model will be used with percentage change as the outcome variable and dose as a factor. Baseline volume will included as a covariate. From the model the adjusted percentage change for each dose will be obtained (with 95% confidence limits) as well as the treatment effect (with 95% confidence limits), defined as percentage change on MAG200 – percentage change on placebo. A p-value will be also obtained to test the null hypothesis no difference between active treatment and placebo against the 2-sided alternative.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
2/07/2018
Date of last participant enrolment
Anticipated
Actual
1/02/2019
Date of last data collection
Anticipated
Actual
1/03/2020
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 307676 0
Commercial sector/Industry
Name [1] 307676 0
Magellan Biologicals Pty Ltd
Country [1] 307676 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Magellan Biologicals Pty Ltd
Address
c/- Minter Ellison
525 Collins Street
Melbourne 3000
Victoria
Country
Australia
Secondary sponsor category [1] 308373 0
None
Name [1] 308373 0
Address [1] 308373 0
Country [1] 308373 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307712 0
Charles Sturt University Human Research Ethics Committee
Ethics committee address [1] 307712 0
The Executive Officer
Human Research Ethics Committee
Charles Sturt University
Locked Bag 588
Wagga Wagga NSW 2678
Ethics committee country [1] 307712 0
Australia
Date submitted for ethics approval [1] 307712 0
04/02/2018
Approval date [1] 307712 0
31/03/2018
Ethics approval number [1] 307712 0
H18021

Summary
Brief summary
Protocol MSC-OAK-002 is a prospective, observational study that runs concurrently with Protocol MSC-OAK-001 (ANZCTR No. ACTRN12617001095358)

Up to 40 subjects with a documented diagnosis of osteoarthritis of the knee, confirmed by X-ray and MRI during Screening, and who have met the eligibility criteria for Protocol MSC-OAK-001 will be offered the opportunity to enrol in this observational study. Following provision of written informed consent and confirmation of eligibility, eligible subjects will commence both protocols on the same day. Subjects enrolled in Protocol MSC-OAK-001 will be on-study for Months 0-3. Subjects enrolled in Protocol MSC-OAK-002 will be on-study for Months 0-12.

All potential subjects will be required to provide written informed consent prior enrolment.

The study is expected to confirm the safety of donor stem cell treatment in osteoarthritis and also the confirm the most effective treatment dose for pain, functional and structural benefit.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108234 0
A/Prof Julien Freitag
Address 108234 0
Melbourne Stem Cell Centre
116-118 Thames St
Box Hill North
Vic 3128
Country 108234 0
Australia
Phone 108234 0
+61 3 9270 8000
Fax 108234 0
Email 108234 0
[email protected]
Contact person for public queries
Name 108235 0
A/Prof Julien Freitag
Address 108235 0
Melbourne Stem Cell Centre
116-118 Thames St
Box Hill North
Vic 3128
Country 108235 0
Australia
Phone 108235 0
+61 3 9270 8000
Fax 108235 0
Email 108235 0
[email protected]
Contact person for scientific queries
Name 108236 0
A/Prof Julien Freitag
Address 108236 0
Melbourne Stem Cell Centre
116-118 Thames St
Box Hill North
Vic 3128
Country 108236 0
Australia
Phone 108236 0
+61 3 9270 8000
Fax 108236 0
Email 108236 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Outcome data of published/reported results
When will data be available (start and end dates)?
Individual de-identified participant data which underlie results reported in this article will be available upon publication. The study protocol will also be available upon publication. Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis. Requests are to be directed to the corresponding author of the article. No end date is given for request of data.
Available to whom?
Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis.
Available for what types of analyses?
Meta-analysis/review articles and for independent validation/review of analysis methodology.
How or where can data be obtained?
Requests are to be directed to the corresponding author of the article (i.e. [email protected])


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.