Efficacy and Safety Study of Intra-Articular Injections of Autologous Peripheral Blood Stem Cells Following Subchondral Drilling Surgery for the Treatment of Articular Cartilage Injury in the Knee

Study Overview
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Brief Summary
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This is a 24-month, multicenter, randomized, open-label, standard treatment-controlled, parallel-group, Phase 2 study for adults with large or complicated knee articular cartilage lesions and are candidates for knee joint cartilage repair surgery. The safety and efficacy of intra-articular injections of peripheral blood stem cells (PBSCs) together with hyaluronic acid (HA) after subchondral drilling surgery will be evaluated to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than a standard treatment (HA injections and physiotherapy regimen).

Detailed Description
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This is a 24-month, multicenter, randomized, open-label, standard treatment-controlled, parallel-group, Phase 2 study for adults with large or complicated knee articular cartilage lesions and are candidates for knee joint cartilage repair surgery. The safety and efficacy of intra-articular injections of peripheral blood stem cells (PBSCs) together with hyaluronic acid (HA) after subchondral drilling surgery will be evaluated to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than a standard treatment (HA injections and physiotherapy regimen).

Official Title
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Multicenter, Randomized, Open-Label, Standard Treatment-Controlled Parallel Group Phase 2 Study to Evaluate Efficacy and Safety of Intra-Articular Injections of Autologous Peripheral Blood Stem Cells and Hyaluronic Acid Adjuvant Therapy Following Subchondral Drilling Surgery for the Treatment of Articular Cartilage Injury in the Knee With an Optional Open-Label Extension for the Standard Treatment-Controlled Group

Conditions
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Articular Cartilage Disorder of Knee, Articular Cartilage; Degeneration

Intervention / Treatment
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* Biological: Autologous peripheral blood stem cells and hyaluronic acid
* Other: Hyaluronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 to 55 years at screening (20 to 57 years for the open-label extension) Present for evaluation and treatment of knee pain, knee swelling, or knee mechanical symptoms due to cartilage lesions Provide written informed consent International Cartilage Repair Society (ICRS) Grade 3 or 4 lesions diagnosis from MRI scans of the target knee All subjects must also satisfy at least 1 of the following inclusion criteria: Isolated knee articular cartilage lesion (single lesion) estimated to be ≥3 cm2 as demonstrated on MRI scanning. Multiple knee articular cartilage lesions (multiple lesions) with at least 1 lesion estimated to be ≥3 cm2 as demonstrated on MRI scanning. Bipolar cartilage defects demonstrated on MRI scanning with at least 1 articular surface lesion to be ≥3 cm2. One or more cartilage defects involving the patello-femoral joint as demonstrated on MRI scanning with at least 1 lesion ≥3 cm2. One or more cartilage defects involving the tibio-femoral joint as demonstrated on MRI scanning with at least 1 lesion to be ≥3 cm2. Previously failed cartilage repair procedures (i.e., microfracture, osteochondral autograft transplantation surgery (OATS), ACI) Exclusion Criteria: Three or more previous surgical interventions on the knee in question. Preoperative flexion deformity greater than 10 degrees. Presence of ligamentous injury which would require reconstruction, varus or valgus deformity requiring osteotomy, or cases that require complex surgery prior to cartilage regeneration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Subjects randomized to the intervention group will undergo subchondral drilling surgery according to standard protocol, and will also receive a regimen of PBSC and HA intra-articular injections and postoperative physiotherapy. | Biological: Autologous peripheral blood stem cells and hyaluronic acid<br>* Regimen of intra-articular PBSC and HA injections and postoperative physiotherapy<br>|
| Active Comparator: Standard treatment<br>Subjects randomized to the standard treatment-controlled parallel group will receive intra-articular HA injections and a physiotherapy regimen. | Other: Hyaluronic acid<br>* Regimen of intra-articular HA injections and postoperative physiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC) score | Subjective IKDC core as a measure of joint function | 24 months | 
| Knee injury and Osteoarthritis Outcome (KOOS) pain subdomain | KOOS pain subdomain score as a measure of joint pain | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS) for pain | Numeric Rating Scale (NRS) for pain | 24 months |