Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001095358
Ethics application status
Approved
Date submitted
12/07/2017
Date registered
27/07/2017
Date last updated
12/10/2021
Date data sharing statement initially provided
12/10/2021
Date results information initially provided
12/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, randomised, double blind, placebo-controlled, single ascending dose study to evaluate the safety and tolerability of allogeneic adipose-derived mesenchymal stem cells injected into patients with osteoarthritis of the knee.
Scientific title
A Phase I, single centre, randomised, double blind, placebo-controlled, single ascending dose (SAD) study to evaluate the safety and tolerability of allogeneic adipose-derived mesenchymal stem cells (MAG200) administered by intra-articular injection to patients with symptomatic osteoarthritis of the knee.
Secondary ID [1] 292325 0
Magellan Biologicals Pty Ltd, MSC-OAK-001
Universal Trial Number (UTN)
U1111-1198-6900
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 303886 0
Condition category
Condition code
Musculoskeletal 303249 303249 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Investigational Product MAG200 is a preparation of allogeneic human adipose-derived mesenchymal stem cells (MSCs) in sterile, clinical grade injectable isotonic solution.
Participants will receive a single dose of Investigational Product (MAG200 / placebo) which will be administered by intra-articular injection into the study knee.
Up to 40 eligible subjects will be randomised into the study in four sequential cohorts. Each cohort will comprise 10 subjects, who will be randomised in a 4 to 1 ratio to active or placebo treatment arms (i.e. 8 active: 2 placebo). Dosing will commence at the lowest dose level of MAG200. An internal Safety Review Team (SRT) will be established to review safety data of the previous cohort to determine if dose escalation to the next dose level is recommended. A maximum of 4 dose levels of MAG200 will be studied: 10 million cells, 20 million cells, 50 million cells and 100 million cells.
Intervention code [1] 298517 0
Treatment: Other
Comparator / control treatment
The Placebo solution will contain sterile, clinical grade injectable isotonic solution.
Placebo will be administered as a single dose via intra-articular injection into the study knee.
Control group
Placebo

Outcomes
Primary outcome [1] 302630 0
Safety and tolerability of MAG200 is the primary outcome. It will be assessed by monitoring adverse events, conducting physical examination, vital signs, ECG, clinical laboratory data and concomitant medication usage.
This is the first time that MAG200 has been given to humans before so possible adverse events are unknown. However based on prior experience with autologous MSC injections, potential adverse events may include pain, swelling and stiffness of the joint into which the Investigative Product has been injected. Study visits will include a physical exam, collection of subject reported adverse events and concomitant medication usage to monitor for these possible side effects or others not yet known of.
Timepoint [1] 302630 0
Changes from Baseline to End of Study (Month 3/Day 84).
Physical exam and vital signs will be assessed at Days 0, 7, 14, 28 and month 3.
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.
Adverse events and concomitant medication use will be captured and assessed from Day 0 to month 3.
Secondary outcome [1] 336562 0
Not applicable
Timepoint [1] 336562 0
Not applicable

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
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 of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation to treatment group is concealed ie. the Investigator / delegate who determines if a person is eligible for inclusion into the study, does not have any influence over, or knowledge of the Investigational Product (IP) the participant is administered.
Eligible subjects will be allocated a Randomisation Number in order of their entry into the study. The Investigator will simply apply the next available Randomisation Number to each subject at the time of entry. The unblinded laboratory technicians will then prepare the IP according to the randomisation schedule. The prepared IP is masked (see details below) and provided to the study site for administration. The unblinded laboratory technicians are independent of the conduct of the study at the study site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomisation schedule will be prepared by a statistician prior to the start of the study. The randomisation schedule will be provided to the site by the study statistician.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Due to differences in appearance between the MAG200 suspension and Placebo solution, two unblinded laboratory technicians, independent of the study conduct, will prepare the syringes of study treatment. The syringes will be covered with black plastic to prevent the identification of the injectable material. Syringes will be over-labelled, with each syringe identifiable by the unique Subject Randomisation Number only.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal sample size calculation will be performed for this study. The sample sizes chosen for this study are based on clinical and regulatory considerations and precedence for first-in-human studies, and have no formal statistical basis. The number of subjects proposed is considered sufficient for this initial study to explore the safety and tolerability of MAG200 in patients with OA of the knee.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/11/2017
Actual
2/07/2018
Date of last participant enrolment
Anticipated
1/02/2019
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
Recruitment postcode(s) [1] 16555 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 296872 0
Commercial sector/Industry
Name [1] 296872 0
Magellan Biologicals Pty Ltd
Country [1] 296872 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] 295875 0
None
Name [1] 295875 0
Address [1] 295875 0
Country [1] 295875 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298098 0
Charles Sturt University Human Research Ethics Committee
Ethics committee address [1] 298098 0
The Executive Officer
Human Research Ethics Committee
Charles Sturt University
Locked Bag 588
Wagga Wagga NSW 2678
Ethics committee country [1] 298098 0
Australia
Date submitted for ethics approval [1] 298098 0
21/07/2017
Approval date [1] 298098 0
18/10/2017
Ethics approval number [1] 298098 0
HREC Protocol Number : H17167

Summary
Brief summary
This Phase I, dose escalation trial will evaluate the safety and tolerability of Magellan Biologicals’ allogeneic (obtained from a donor) adipose-derived mesenchymal stem cells (MAG200) when injected into the knees of patients with osteoarthritis of the knee. This is the first time MAG200 will be given to human subjects who are not genetically related to the donor of the stem cells. Up to 40 volunteers aged between 18-65 years, will be enrolled. A maximum of four dose levels of MAG200 will be tested with 10 subjects in each dose level cohort; 8 subjects receiving MAG200 and 2 receiving placebo. The subjects and study team will not know which treatment a subject receives. Dosing will commence at the lowest dose level of MAG200 and a Safety Review Team will review the safety data of each dose level cohort before allowing progression to the next dose level to occur.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75982 0
A/Prof Julien Freitag
Address 75982 0
Melbourne Stem Cell Centre
116-118 Thames St
Box Hill North
Vic 3128
Country 75982 0
Australia
Phone 75982 0
+61 3 9270 8000
Fax 75982 0
Email 75982 0
[email protected]
Contact person for public queries
Name 75983 0
Mr Peter Hansen
Address 75983 0
Magellan Biologicals Pty Ltd
c/- Minter Ellison
525 Collins Street
Melbourne 3000
Victoria
Country 75983 0
Australia
Phone 75983 0
+61 3 9787 0102
Fax 75983 0
+61 3 8672 5928
Email 75983 0
[email protected]
Contact person for scientific queries
Name 75984 0
A/Prof Julien Freitag
Address 75984 0
Melbourne Stem Cell Centre
116-118 Thames St
Box Hill North
Vic 3128
Country 75984 0
Australia
Phone 75984 0
+61 3 9270 8000
Fax 75984 0
Email 75984 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.