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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Device: Cross-linked intra-articular hyaluronic acid; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Antalya, Turkey
    • Antalya Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cross-linked intra-articular hyaluronic acid; Cross-linked intra-articular hyaluronic acid (90 mg 3 ml cross-linked hyaluronic acid)	Device: Cross-linked intra-articular hyaluronic acid; 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.
Placebo Comparator: Placebo; Intra-articular isotonic saline solution (3 ml 0.9% isotonic saline) at the same dose as the treatment arm	Other: Placebo; 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.; Other Names: 3 ml isotonic saline solution

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Semikal Technology
• Collaborators: Antalya Training and Research Hospital
• Investigators: Study Director: Aslıhan Kara, Semikal Technology

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: October 25, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 21, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: knee osteoarthritis; hyaluronic acid; viscosupplementation; intraarticular injection
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Immunologic Factors; Physiological Effects of Drugs; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: SEM-ART1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study protocol will be published as an article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No