Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001018202
Ethics application status
Approved
Date submitted
6/02/2009
Date registered
24/11/2009
Date last updated
20/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised, double-blind, comparator study to assess the safety & tolerability of a single injection into the knee joint of MSB-CAR001 when combined with Hyaluronan compared to Hyaluronan alone in patients who have recently undergone an Anterior Cruciate Ligament Reconstruction.
Scientific title
A randomised, double-blind, comparator study to assess the safety & tolerability of a single injection into the knee joint of two different doses of MSB-CAR001 combined with Hyaluronan compared to Hyaluronan alone in patients who have recently undergone an Anterior Cruciate Ligament Reconstruction.
Secondary ID [1] 799 0
Nil
Universal Trial Number (UTN)
Trial acronym
MSB-CAR001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anterior Cruciate Ligament (ACL) reconstruction following an initial, unilateral acute ACL injury. 4280 0
Osteoarthritis post ACL repair 4720 0
Condition category
Condition code
Musculoskeletal 4510 4510 0 0
Osteoarthritis
Surgery 4511 4511 0 0
Other surgery
Musculoskeletal 237043 237043 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single injection of Mesenchymal Precursor Cells MSB-CAR001, of 75 million dose mixed with 2ml Hyaluronan and injected into knee
Intervention code [1] 4012 0
Rehabilitation
Intervention code [2] 4487 0
Prevention
Comparator / control treatment
The treatment group will receive 75 Million Mesenchymal Precursor Cells mixed with 2ml Hyaluronan and injected directly into the knee joint . The control group will receive 2ml of hyaluronan alone injected directly into the knee joint. The knee injection procedure takes approximately 10 minutes (inlcuding preparation time).
Control group
Active

Outcomes
Primary outcome [1] 5390 0
To evaluate the safety & tolerability of a single injection of allogeneic Mesenchymal Precursor Cells (MPCs) combined with Hyaluronan. A physical examination will be performed at the various study visits to report clinical signs & symptoms. A study specific knee examination noting any changes or new findings since baseline as adverse events (e.g. joint swelling, pain) will be performed each subsequent evaluation through the course of the study. All participants will be observed for at least 120 minutes following the injection of study treatment.
Timepoint [1] 5390 0
Screening, 10 days, 4-6 weeks post ACL surgery, randomisation/treatment injection day, 5 days, 28 days post knee injection, 8, 12, 26, 36, 52, 78 and 104 weeks post treatment/knee injection.
Secondary outcome [1] 262407 0
To evaluate the safety & efficacy of a single injection of allogeneic MPCs + Hyaluronan compared to Hyaluronan alone by observing changes prospectively to cartilage in the knee joint post ACL reconstruction via X-Ray and MRI
Timepoint [1] 262407 0
screening visit, 4-6 weeks post ACL surgery, 26, 52 and 104 weeks post knee treatment/injection.

Eligibility
Key inclusion criteria
1. Males or females at least 18 years of age, but not older than 40;
2. ACL injury requiring reconstruction with bone bruising evident on preoperative Magnetic Resonance Imaging (MRI) scan at screen or within 6 months of initial ACL injury;
3. Have undergone unilateral ACL reconstruction surgery within six months of injury;
4. Clinically stable knee after reconstruction – International Knee Documentation Committee clinical knee examination at time of surgery after reconstruction to be grade normal or nearly normal;
5. Willing and able to undertake a standardized rehabilitation protocol as assessed by surgeon;
6. ACL graft used is autograft Hamstring;
7. Willingness to participate in follow-up for 24 months from the time of initial treatment;
8. Ability to understand and willingness to sign consent form;
9. If a female is of childbearing potential , then she must:
- Have a confirmed negative urine pregnancy test result at screening, before surgery and prior to the administration of the study treatment.
- Agree to use a medically reliable method of preventing conception for the duration of the study
- Male participants with partners of childbearing potential must be willing to use a medically reliable method of preventing conception for the duration of the study.
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant or breast feeding or planning to become pregnant during the study;
2. Known sensitivities to bovine (cow), murine (mouse), chicken products and/or dimethylsulfoxide (DMSO);
3. Known allergies to products from birds such as feathers, eggs or poultry;
4. Previous allergic reaction to Hyaluronan;
5. Systemic or local infection at the screen visit or at the time of the study injection;
6. History of any autoimmune disease, such as, systemic lupus erythematosus, Addison’s disease, Crohn’s disease, or rheumatoid arthritis;
7. Treatment with immunosuppression therapy within 6 months prior to screen (visit 1);

8. Chronic (at least 7 consecutive days) of systemic corticosteroids at a dose equivalent to > 10 mg/day of prednisolone within 14 days prior to screen (Visit 1);
9. Acute or chronic infectious disease, including but not limited to human immunodeficiency virus (HIV);
10. Treatment and /or uncompleted follow-up treatment of any investigational therapy within 6 months before the procedure and /or intent to participate in any other investigational drug or cell therapy study during the 24 month follow-up period of this study;
11. Recipient of prior allogeneic stem cell/progenitor cell therapy;
12. Undergoing a simultaneous procedure to the opposite knee;
13. Injury is work related and covered by workers compensation;
14. 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);
15. Has antibody specificities to donor Human Leukocyte Antigens (HLA);
16. History or current evidence of alcohol or drug abuse or is a recreational user of illicit drugs or prescription medications;
17. Significant damage to the collateral or posterior ligaments of the knee;
18. Meniscal injury requiring more than a 1/3 resection or more than a single suture to reconstruction or a reconstruction that will alter the usual ACL rehabilitation;
19. History of prior surgery to the study knee joint;

20. History of malignancy (excluding basal cell carcinoma that has been successfully excised);

21. Chondral lesions noted at time of surgical reconstruction greater than Grade 1a on any surfaces;

22. Intra-articular steroid or corticosteroid or Hyaluronan injections in preceding 3 months to the affected joint;

23. Diffuse synovitis at time of surgery for the ACL reconstruction;


24. Indwelling metal of any description which precludes MRI examination, such as but not limited to, indwelling pacemaker, cerebral aneurysm clips, or electrical indwelling device such as bone stimulator or anything that would preclude participant from undergoing screening MRI;

25. Not willing to return for required follow-up visits or there is a clear demonstration of likely poor compliance;

26. Any other medical condition that, in the judgment of the Principal Investigator/Investigators, would prohibit the patient from participating in the study.
27. Patient is legally or mentally incapacitated;

28. Prisoners or participants who are involuntarily incarcerated;

29. Participants who are compulsorily detained for treatment of a psychiatric disorder.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients enrolled in the study will be randomised to receive 75 Million MPCs combined with Hyaluronan or Hyaluronan alone. Cohort A: 12 study participants will be randomly assigned to receive a single injection into the knee joint 4-6 weeks post ACL reconstruction of either 75 million MPCs + Hyaluronan or Hyaluronan alone. Cohort B: 12 study participants will be randomly assigned to receive a single injection into the knee joint 4-6 weeks post ACL reconstruction of 75Million MPCs + Hyaluronan or Hyaluronan alone.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation concealment to be done by contacting the central lab 'off site' storing the study treatment and requesting the randomisation/treatment assignment
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/03/2009
Actual
19/03/2009
Date of last participant enrolment
Anticipated
Actual
15/10/2012
Date of last data collection
Anticipated
Actual
2/01/2015
Sample size
Target
24
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4462 0
Commercial sector/Industry
Name [1] 4462 0
Mesoblast Ltd
Country [1] 4462 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] 4021 0
None
Name [1] 4021 0
Address [1] 4021 0
Country [1] 4021 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6965 0
Cabrini Human Research Ethics Committee
Ethics committee address [1] 6965 0
Malvern East
Ethics committee country [1] 6965 0
Australia
Date submitted for ethics approval [1] 6965 0
Approval date [1] 6965 0
16/01/2009
Ethics approval number [1] 6965 0
04-15-12-08

Summary
Brief summary
This study is primarily designed to assess the safety of two different doses of allogeneic Mesenchymal Precursor Cells (MPCs) combined with Hyaluronan when injected into the knee joint following Anterior Cruciate Ligament reconstruction. Long term safety, tolerability and efficacy of a single injection of two different doses of allogeneic MPCs + Hyaluronan compared to Hyaluronan alone will be assessed at 6, 12 and 24 months following MPC injection. This study aims to provide prelimanary data to support dose selection for future studies.
Trial website
www.mesoblast.com
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29256 0
Dr Andrew Shimmin
Address 29256 0
The Melbourne Orthopaedic Group
33, The Avenue
Windsor 3181
Victoria
Country 29256 0
Australia
Phone 29256 0
+61 3 9529 3333
Fax 29256 0
Email 29256 0
ashimmin@optusnet.com.au
Contact person for public queries
Name 12503 0
Mr Michael DiMuro
Address 12503 0
505 Fifth Avenue
Level 3
New York, NY 10017
Country 12503 0
United States of America
Phone 12503 0
+1 (212) 993-7905
Fax 12503 0
+1 212 880 2061
Email 12503 0
ichael.DiMuro@mesoblast.com
Contact person for scientific queries
Name 3431 0
Mr Michael DiMuro
Address 3431 0
505 Fifth Avenue
Level 3
New York, NY 10017
Country 3431 0
United States of America
Phone 3431 0
+1 (212) 993-7905
Fax 3431 0
+1 212 880 2061
Email 3431 0
ichael.DiMuro@mesoblast.com

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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