A Study to Determine the Safety and Efficacy of TG-C in Subjects With Symptomatic Early Hip Osteoarthritis

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Determine the Efficacy, Safety, and Dosing of TG-C in Adult Subjects with Symptomatic Early Hip Osteoarthritis. TG-C will be administered to the target hip by a single ultrasound (or fluoroscopy)-guided, intra-articular injection with image capture showing correct injection of study drug into the femoroacetabular joint. Patients will be followed for 12 months for safety and efficacy.

Detailed Description
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This protocol is designed to assess the safety and efficacy of TG-C in treating symptoms of osteoarthritis of the hip and determining disease modifying effects of TG-C. TG-C will be compared to normal saline as a control. Safety will be evaluated by observation of the injection site for irritation or other effects, the incidence and severity of adverse events, and changes in physical examination findings, radiographic criteria, and laboratory tests. Patients will be followed for 12 months for both safety and efficacy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Determine the Efficacy, Safety, and Dosing of TG-C in Adult Subjects With Symptomatic Early Hip Osteoarthritis

Conditions
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Degenerative Osteoarthritis

Intervention / Treatment
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* Biological: TG-C
* Biological: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 80 years old The subject has a diagnosis of Grade ≤2 primary OA of the target hip Pain ≥ 40 on VAS scale The subject has groin pain that is elicited by hip rotation on physical examination No history of significant organ system disorders. Body mass index (BMI) <40 kg/m2 Systolic blood pressure of 100 to 160 mmHg and diastolic blood pressure of 60 to 90 mmHg. Using birth control Written informed consent Exclusion Criteria: The subject exhibits severe symptoms in the target hip that result in difficulty or an inability to walk. The subject has severe hip OA ipsilateral to the target hip. Previous cartilage transplantation procedure to the injured cartilage surface. Major injury to the target hip within 12 months of screening. Active dermal ulcer or infection in the proximity of the target hip within 1 month before screening. The subject has had surgery on the target hip within the last 6 months. Total hip replacement surgery or other surgery on the target hip in the next 12 months. MRI indicates bone marrow infiltration, fracture, osteonecrosis/bone infarct, osteochondritis dissecans, tumor, moderate to severe dysplasia, avascular necrosis, post-traumatic arthritis, transient osteoporosis, slipped-cap femoral epiphysis, juvenile idiopathic arthritis, or axial juvenile spondyloarthritis. Hip conditions including but not limited to any autoimmune or infectious cause for arthritis; metabolic joint disease; neuropathic disorders, groin pain from non-orthopedic sources, or tumors, congestive heart failure, or chronic kidney disease. Uncontrolled diabetes based on a hemoglobin A1c (HbA1c) value >8% at the screening Visit. Increased risk for post-procedure bleeding or post-procedure infection. Ongoing infectious disease, including, but not limited to, HIV, hepatitis C, or current or prior hepatitis B. Cognitive impairment that would limit his/her ability to provide informed consent or to complete assessments and questionnaires. 1 year history of drug or alcohol abuse. Contraindication to or cannot undergo MRI. Active malignancy within the last 5 years. Pregnant or is lactating. Taken steroidal or NSAIDs within 14 days before the Baseline Visit Using topical analgesics on the target hip Receiving chronic narcotic treatment at screening. Received any injection to the target hip within the 3 months before the Baseline Visit. Taking antiplatelet or anticoagulants. Participated in an investigational study within 13 weeks before the Screening Visit or in the next 25 months. Unable to comply with the requisite study follow-up and all of the follow-up office visits.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment (TG-C)<br>TG-C at 1.0 x 10e7 cells per single 2 mL intraarticular injection | Biological: TG-C<br>* 2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1.<br>* Other names: TissueGene-C;|
| Active Comparator: Active Treatment 2 (TG-C)<br>TG-C at 3.0 x 10e6 cells per single 2 mL intraarticular injection | Biological: TG-C<br>* 2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1.<br>* Other names: TissueGene-C;|
| Placebo Comparator: Placebo Control (Normal Saline)<br>Normal saline, single 2 mL intraarticular injection | Biological: Placebo Control<br>* 2 mL normal saline injection<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hip Pain as Assessed by VAS | Assessment of change from baseline in target hip pain using the Visual Analog Scale (VAS). The VAS is a method for the assessment of the intensity of pain. The VAS is a horizontal line, 100 mm in length and anchored by word descriptors at each end (no pain, very severe pain). The patient marks on the line at the point that represents their current state. The VAS score is determined by measuring in millimeters from the left hand end to the point of the mark. The score ranges from 0 or no pain to 100 very severe pain. | Baseline to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hip Disability and Osteoarthritis Outcome Score (HOOS) | The HOOS questionnaire was built upon the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC®). Questions from the WOMAC® were used as the basis for the survey, and 2 dimensions were added: sport and recreation and hip-related quality of life. The HOOS is composed of 40 questions in 5 subscales: Pain (10 items), Symptoms (5 items), Activity of Daily Living (17 items), Sport and Recreation Function (4 items), and Hip-Related Quality of Life (4 items). A total score, ranging from 0 to 100 is calculated. Higher scores represent better functioning. | Baseline to Month 12 | 
| Timed Up and Go Test (TUG) | The TUG test is used to determine the time needed to progress from sitting to standing and walking. In addition, the test helps to evaluate the probability for falls. The individual starts in a seated position in a chair with armrests and, upon command, stands up, walks 3 meters, turns around, walks back to the chair, and sits down. The time stops when the subject is seated. The use of walking aids should be recorded and kept consistent between tests. | Baseline to Months 1, 3, 6, 9, and 12 | 
| UCLA Activity Score | The UCLA Activity Score includes 10 statements that cover the range of activity states from being wholly inactive, dependent on others, and cannot leave residence to regularly participate in impact sports. The respondents are instructed to select one statement that is most representative of their current activity. Lower scores on the scale reflect a low level of activity and higher scores reflect more activity. | Baseline to Months 1, 3, 6, 9, and 12 | 
| Joint Space Width (JSW) on standing X-ray | To evaluate the effects of 2 dose levels of TG-C on the structural features of the hip joint | Baseline to Month 12 | 
| WOMAC® (Western Ontario and McMaster Universities Osteoarthritis Index) total score | To evaluate the effects of 2 dose levels of TG-C on symptoms of OA of the hip. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | Baseline to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hip