Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis

Study Overview
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Brief Summary
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The goal of this clinical study is to determine if a single injection of 1 or more dose levels of adeno-associated virus (AAV) gene therapy (GNSC-001) is safe and tolerated compared to placebo in participants with painful osteoarthritis (OA) of the knee.

Official Title
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A Phase 1b, Randomized, Double-Blinded, Placebo-Controlled Dose Ranging Study to Evaluate Safety, Tolerability and Pharmacodynamics of a Single Intra-articular Injection of GNSC-001 Gene Therapy in Subjects With Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee, Osteo Arthritis Knee, Knee Osteoarthritis

Intervention / Treatment
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* Genetic: GNSC-001
* Drug: transient immune-modulation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: OA in at least one knee (the 'target knee'), confirmed using centrally read X-ray with a Kellgren-Lawrence (KL) score of 2 or 3 Western Ontario & McMaster University Osteoarthritis Index (WOMAC) pain score ≥ 20 (on a 50-point numerical rating scale) in the target knee during the seven days prior to Screening Persistent moderate to severe symptoms in the target knee, despite failure or intolerance of a 3-month trial of at least 2 conservative therapies (e.g., activity modification, weight loss, physical therapy, opioids, and anti-inflammatory medications, and injection of hyaluronic acid or steroids) Presence of synovial fluid on ultrasound and/or high likelihood of successful extraction of synovial fluid Negative pregnancy test at Screening and Baseline (subjects of childbearing potential [SOCBP]) Key Exclusion Criteria: Current or documented history of inflammatory arthritis (such as gout or rheumatoid arthritis), inflammation of connective tissue, or other immunological disease Any form of joint degeneration as part of another syndrome (e.g., Ehler's Danlos, Stickler syndrome, etc.) Surgery in the target knee within the 6 months prior to screening Previous partial or total joint replacement in target knee Significant and clinically evident malalignment of the target knee that would impact the subject's function, as determined by the Investigator Body mass index (BMI) > 38 kg/m2 Clinically significant abnormal laboratory values at Screening in laboratory parameters that in the opinion of the Investigator, could represent a potential risk to participant safety: Plans to have, elective surgery of other joints or spine or intra-articular injections in the target knee, within the next 12 months

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: GNSC-001 (low dose)<br> | Genetic: GNSC-001<br>* intra-articular injection<br>* Other names: sc-rAAV2.5IL-1Ra;|
| Experimental: GNSC-001 (low dose) + transient immune-modulation<br> | Genetic: GNSC-001<br>* intra-articular injection<br>* Other names: sc-rAAV2.5IL-1Ra;Drug: transient immune-modulation<br>* oral<br>|
| Experimental: GNSC-001 (high dose)<br> | Genetic: GNSC-001<br>* intra-articular injection<br>* Other names: sc-rAAV2.5IL-1Ra;|
| Experimental: GNSC-001 (high dose) + transient immune-modulation<br> | Genetic: GNSC-001<br>* intra-articular injection<br>* Other names: sc-rAAV2.5IL-1Ra;Drug: transient immune-modulation<br>* oral<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* intra-articular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) |  | Month 12 | 
| Severity of TEAEs and SAEs |  | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in synovial Interleukin-1 Receptor Antagonist (IL-1Ra) levels over time, from Baseline |  | Baseline to Month 1, 3, 6, 12, and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene therapy, Adeno-associated virus, Intra-articular, GNSC-001, Genascence, Knee pain, Knee arthritis, Osteoarthritis