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.

Phase 1

Completed

• Conditions: Surgery - Other surgery; Anterior Cruciate Ligament (ACL) reconstruction following an initial, unilateral acute ACL injury.; Osteoarthritis post ACL repair; Musculoskeletal - Osteoarthritis; Musculoskeletal - Osteoporosis

• Registration Number: ACTRN12609001018202
• Lead Sponsor: Mesoblast Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-11-24
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 24

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.

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

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.[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 Measures

Name	Time	Method
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[screening visit, 4-6 weeks post ACL surgery, 26, 52 and 104 weeks post knee treatment/injection.]