Effectiveness and Safety of Intra-articular SEMICAL GEL-B CROSS Therapy in Knee Osteoarthritis (SEM-ART1)

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the effectiveness and safety of intra-articular injection of a cross-linked sodium hyaluronate; SEMICAL GEL-B CROSS, in knee osteoarthritis. Primary objectives: The aim of this study is to obtain short- and long-term clinical data on the performance and safety of intra-articular injection of SEMICAL GEL B-CROSS, produced and marketed by Semical Biosurgery incorporated company, in knee osteoarthritis patients. It is also aimed to monitoring known adverse events and complications, detecting previously unknown adverse events and complications, to identify and analyze emerging risks based on real-life data. Participants will receive intra-articular injection of either a cross-linked sodium hyaluronate (SEMICAL GEL-B CROSS); or placebo (isotonic saline solution) at baseline, and will be followed-up for one year to compare the effectiveness and safety of the given therapy.

Detailed Description
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The study is a randomized controlled, double-blind, two-armed, single-center and cross-over study. After a maximum screening period of 28 days, patients with Kellgren & Lawrence Stage II and III knee osteoarthritis will be randomly assigned to one of the two treatment arms on the day of injection, which is considered Day 0. These treatment arms are: Group 1: Treatment Arm - Cross-linked intra-articular hyaluronic acid (90 mg 3 ml cross-linked hyaluronic acid) Group 2: Control Arm - Intra-articular isotonic saline solution (3 ml 0.9% isotonic saline) A safety visit will be made 7-10 days after administration of the treatment injection and the injection site will be visually evaluated for local reactions. In addition, an inquiry for injection-related adverse events will also be conducted. Treatment responses of patients in both groups will be evaluated by a separate researcher blinded to study treatment with predefined objective response criteria. At the 3rd month visit, the patients in both groups will be crossed-over and those who received a placebo at baseline will receive a hyaluronic acid injection at the 3rd month, while those who receive a hyaluronic acid injection at baseline will receive a placebo at the 3rd month. Efficacy evaluations will continue to be made at every three months for one year.

Official Title
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Safety and Effectiveness of Intra-articular Injection of a Cross-linked Sodium Hyaluronate in Knee Osteoarthritis: A Randomized, Prospective, Double-blind, Placebo-controlled, Cross-over, Post-marketing Clinical Follow-up Study

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: Cross-linked intra-articular hyaluronic acid
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 and over, both male and female Diagnosed with clinical knee osteoarthritis according to the American College of Rheumatology (ACR) criteria, with Kellgren & Lawrence stage II and III osteoarthritic findings on antero-posterior knee radiographs Able to provide written informed consent Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cross-linked intra-articular hyaluronic acid<br>Cross-linked intra-articular hyaluronic acid (90 mg 3 ml cross-linked hyaluronic acid) | Device: Cross-linked intra-articular hyaluronic acid<br>* Patients in the treatment arm will receive 3 ml, 90 mg hyaluronic acid injection intra-articularly, while the ones in the placebo arm will receive 3 ml saline injection intra-articularly. The groups will be crossed-over at 3rd month.<br>|
| Placebo Comparator: Placebo<br>Intra-articular isotonic saline solution (3 ml 0.9% isotonic saline) at the same dose as the treatment arm | Other: Placebo<br>* Patients in the treatment arm will receive 3 ml, 90 mg hyaluronic acid injection intra-articularly, while the ones in the placebo arm will receive 3 ml saline injection intra-articularly. The groups will be crossed-over at 3rd month.<br>* Other names: 3 ml isotonic saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores | The alteration in pain arising from knee osteoarthritis will be assessed in correlation with changes in WOMAC pain scores at baseline, 3 months, 6 months, 9 months, and 12 months. | Baseline, 3 months, 6 months, 9 months, and 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) function score | The alteration in pain arising from knee osteoarthritis will be assessed in correlation with changes in WOMAC pain scores at baseline, 3 months, 6 months, 9 months, and 12 months. | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Changes in knee functions | The alteration in function arising from knee osteoarthritis will be assessed in correlation with changes in WOMAC pain scores at baseline, 3 months, 6 months, 9 months, and 12 months. | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Changes in knee flexor muscle strength | Knee flexor muscle strength assessed by myometer | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Changes in knee extensor muscle strength | Knee extensor muscle strength assessed by myometer | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Changes in knee functions during 5 times sit to stand test | 5 times sit to stand test | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Changes in knee functions by 6MWT (6 Minute Walking Test) | 6 minute walking test | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Change in the need for analgesic drug from pre-treatment to post-treatment | Will be assessed by patient diary | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Change in quality of life | Will be assessed by 36-item Short Form Survey | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Change in knee pain during movement and rest | Will be assessed by Visual Analogue Scale 1-10 (1: no pain, 10: very much pain) | Baseline, 3 months, 6 months, 9 months, and 12 months. | 
| Local reactions in the injection site | A safety visit will be performed 7-10 days after administration of the treatment injection and the injection site will be visually assessed for local reactions. | 7-10 days post-injection | 
| Adverse events throughout the entire study period | Adverse events will be questioned throughout the entire study period | Through study completion, an average of 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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knee osteoarthritis, hyaluronic acid, intraarticular injection, viscosupplementation