Phase 1/2 Clinical Study of TPX-115 in Patients With Partial-Thickness Rotator Cuff Tear

Study Overview
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Brief Summary
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Rotator cuff tear is one of the most common shoulder diseases and conservative treatment is commonly used for tears involving ≤50% of tendon thickness. Since conventional conservative treatments are not fundamental to repair tendon tissue, there is a growing need of new therapy to improve structural outcome. This study assesses the safety and efficacy of allogeneic fibroblasts on partial-thickness rotator cuff tear. The primary outcome is change in American Shoulder and Elbow Surgeons (ASES) score at 24 weeks after TPX-115 injection. Secondary outcomes include changes from baseline in Visual Analogue Score (VAS) pain score, functional evaluations including Range of Motion (ROM), Constant Score (CS), ASES score and Simple Shoulder Test (SST) at 4, 12 and 24 weeks after administration and structural evaluation using MRI at 24 weeks after injection.

Official Title
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A Multi-center, Randomized, Independent Evaluator-blinded, Subject-blinded, Placebo-controlled, Phase 1/2 Clinical Study to Evaluate Safety and Efficacy of TPX-115 in Patients With Partial-Thickness Rotator Cuff Tear

Conditions
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Rotator Cuff Injuries

Intervention / Treatment
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* Biological: TPX-115
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must; Be 19 years of age or older. Have partial-thickness rotator cuff tear, ≤50% of tendon thickness or of Ellman grade I, II assessed by MRI. Have unilateral shoulder pain lasting more than 3 months despite conservative treatment and VAS pain score ≥5 at screening. Understand fully the study and voluntarily sign the informed consent for participation in the study. Exclusion Criteria: Participants with any of the following conditions will be excluded unless stated otherwise; Have partial-thickness rotator cuff tear larger than 50% of tendon thickness or of Ellman grade III, or full-thickness rotator cuff tear confirmed by MRI. Have prior medical history of shoulder surgery on the torn rotator cuff or the upper part of shoulder within 6 months prior to screening visit (shoulder trauma, fracture, upper cervical spine surgery, etc.). Have had subacromial or intra-articular injections on the affected shoulder within 3 months prior to screening visit. Have had received systemic steroid or immunosuppressive agents within 4 weeks prior to screening visit. Have been diagnosed with the following diseases. Inflammatory joint diseases Other shoulder diseases which may cause shoulder pain or functional disorder Autoimmune diseases Active hepatitis B or C HIV Ab positive Malignant tumors within the last 5 years Coagulopathy Genetic disorders related to fibroblasts of collagen Other serious diseases deemed to affect the results of the study Have allergies to bovine proteins or gentamicin. Be pregnant, breastfeeding, planning pregnancy or unwilling to use of contraceptive suggested in this study. Have participated in other clinical trials and received investigational agents within 4 weeks of this study Be deemed inadequate for the study by investigators.

Ages Eligible for Study
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Minimum Age: 19 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TPX-115<br>Subjects receive ultrasound-guided intratendinous injection of TPX-115 | Biological: TPX-115<br>* Ultrasound-guided intratendinous injection of allogeneic fibroblasts(TPX-115)<br>|
| Placebo Comparator: Placebo<br>Subjects receive ultrasound-guided intratendinous placebo injection | Other: Placebo<br>* Ultrasound-guided intratendinous placebo injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in shoulder score of American Shoulder and Elbow Surgeons (ASES) | ASES shoulder score is derived from the Visual Analogue Scale (VAS) score for pain and activities of daily living score. The total score - maximum of 100 points - is weighted 50% for pain and 50% for function. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in shoulder score of American Shoulder and Elbow Surgeons (ASES) | ASES shoulder score is derived from the Visual Analogue Scale (VAS) score for pain and the activities of daily living score. The total score - maximum of points - is weighted 50% for pain and 50% for function. | 4, 12 weeks | 
| Change in pain score of Visual Analogue Scale (VAS) | VAS pain score is measured on a scale of 0 (no pain) to 10 (worst pain imaginable). | 4, 12, 24 weeks | 
| Change in Range of Motion (ROM) | Measurement of ROM for forward elevation, external rotation at 90º abduction, external rotation at side and internal rotation at back. | 4, 12, 24 weeks | 
| Change in Constant score (CS) | The CS total score (100) = Pain (15) + Activity of Daily Living (20) + Mobility (40) + Strength(25) | 4, 12, 24 weeks | 
| Change in Simple Shoulder Test (SST) Score | SST assesses functional disability of the shoulder (function related to pain, function/strength and Range of Motion). | 4, 12, 24 weeks | 
| Change in tear size on Magnetic Resonance Image (MRI) | Tear size is assessed by an independent evaluator. | 24 weeks | 
| Change in tendon thickness on Magnetic Resonance Image (MRI) | Tendon thickness is assessed by an independent evaluator. | 24 weeks | 
| Change in tear/footprint on MRI | Ratio of tear lengths to whole footprint length is measured by an independent evaluator. | 24 weeks | 
| Change of tendinosis on MRI | Tendinosis is assessed with tendinosis grading system by an independent evaluator. (0: normal, 1: mild, 2: moderate, 3: marked) | 24 weeks |