Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren/Lawrence Grade 2 or 3 OA of the Knee

Degenerative Osteoarthritis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 3 Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03291470
• Other study ID #: TGC-15302
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 9, 2021
• Est. completion date: March 6, 2026

Study information

• Verified date: April 2024
• Source: Kolon TissueGene, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, double-blind, placebo-controlled, multi-center, phase 3 study to determine the efficacy and safety of TG-C in subjects with Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee, Osteoarthritis Research Society International (OARSI) medial joint space narrowing (JSN) Grade 1 or 2 of the knee joint. TG-C is to be administered by a single intra-articular injection to the damaged joint area via ultrasound guidance. Patients will be followed for 24 months for safety and efficacy.

Description:

This protocol is designed to assess the safety and efficacy of TG-C in treating symptoms of osteoarthritis of the knee and determining disease modifying effects of TG-C. This study is intended for the treatment of patients with K&L Grade 2 and 3 osteoarthritis and OARSI JSN Grade 1 and 2. Assessments will be made on both the symptomatic effects of pain (VAS), function (WOMAC), and Quality of Life (SF-12) as well as the physical effects (JSW, MRI evaluations of whole knee joint organ tissues and structure) and biochemical biomarkers. This is a placebo-controlled study, TG-C will be compared to normal saline as a control. Additionally, this protocol is designed to evaluate the safety of TG-C. 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 24 months for both safety and efficacy with annual cancer surveillance questionnaires through 15 years post dose for subjects who do not enroll in the Long Term Safety study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 511
• Est. completion date: March 6, 2026
• Est. primary completion date: March 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Aged 40 or older
• BMI between 18.5 and 40
• KL Grade 2 or 3 knee OA
• OARSI Grade 1 or 2 medial JSN
• Pain >= 40 on VAS scale
• Written informed consent
• Using birth control

Exclusion Criteria:

• Knee symptoms that result in difficulty or inability to walk
• Knee effusion >2+
• Has Grade 3 OARSI JSN
• MRI exam indicates fracture or tumor
• Has a positive result on RCR testing at screening
• Has taken NSAIDS with 14 days of baseline
• Has taken steroidal anti-inflammatory or biologic therapy medication within 2 months of baseline
• Chronic (>21 days) narcotic use
• Recent history (within 1 year) of drug or alcohol abuse
• Pregnant or lactating
• Has received injection to target knee within 2 months prior to study entry
• History of various disorders of the knee including but not limited to rheumatoid arthritis, psoriatic arthritis, autoimmune disorder, chondrocalcinosis, gout, hemochromatosis, villonodular synovitis, or synovial chondromatosis
• Severe hip osteoarthritis ipsilateral to the target knee
• Ongoing infectious disease including but not limited to HIV, HTLV-1, VSV-G, HBV, or HCV.
• Clinically significant congestive heart failure, hepatic disease, kidney disease, adrenal insufficiency, acromegaly, uncontrolled hyper- or hypothyroidism, or non-specified uncontrolled endocrine disorder.
• Uncontrolled diabetes based on a HbA1c > 8% at screening.
• Documented active malignancy within the last 5 years except for basal cell carcinoma, squamous cell carcinoma, and benign pigmented nevi.

Related Conditions & MeSH terms

• Degenerative Osteoarthritis
• Osteoarthritis

Intervention

Biological:
• TG-C
2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1
• Placebo Control
2 mL normal saline intraarticular injection

Locations

Country	Name	City	State
United States	Steve Sitar	Anaheim	California
United States	Stuart Silverman	Beverly Hills	California
United States	Richard Radnovich	Boise	Idaho
United States	Igor Grosman	Brooklyn	New York
United States	Edward Tavel	Charleston	South Carolina
United States	Thomas Schnitzer	Chicago	Illinois
United States	Miguel Trevino	Clearwater	Florida
United States	Samy Metyas	Covina	California
United States	James Lilly	Dallas	Texas
United States	Priyesh Mehta	Dayton	Ohio
United States	Jan Hommen	Doral	Florida
United States	John Solic	Durham	North Carolina
United States	Bassil Aish	Huntington Beach	California
United States	Peter Hanson	La Mesa	California
United States	Duane C Anderson	Las Vegas	Nevada
United States	Manjoo Sharma	Lewisville	Texas
United States	Jonathan Samuels	New York	New York
United States	Haresh Boghara	Red Oak	Texas
United States	Nathan Rimmke	Rochester Hills	Michigan
United States	Larkin Wadsworth	Saint Louis	Missouri
United States	Charles Andrews	San Antonio	Texas
United States	Leonel Reyes	San Antonio	Texas
United States	John Beckes	San Diego	California
United States	David Scott	Spokane	Washington
United States	Nebojsa Skrepnik	Tucson	Arizona
United States	Mira Baron	West Palm Beach	Florida
United States	Jeremy Hoff	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Kolon TissueGene, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Radiography for Structural Change in Knee Joint	Evaluate structural changes of the knee joint as determined by radiography (X-ray)	24 months
Other	Efficacy of TG-C with Regard to Knee Function via WOMAC Total Score	Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score	Week 1, Months 3, 6, 9, 12, 18, and 24
Other	Efficacy of TG-C with Regard to Knee Function via WOMAC Pain, Function, and Stiffness Scores	Evaluate the efficacy of TG-C with regard to knee function via WOMAC® pain, function, and stiffness scores	24 months
Other	Efficacy of TG-C with Regard to Knee Function via VAS Pain Score	Evaluation of the efficacy of TG-C with regard to knee function via VAS pain score at time points other than Month 12	Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24
Other	OMERACT-OARSI Responder Analysis	Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria	12 and 24 months
Other	European Quality of Life-Five Dimensions Questionnaire (EQ-5D-5L)	Evaluate health outcomes using the European Quality of Life-Five Dimensions Questionnaire (EQ-5D-5L)	Baseline and Months 3, 6, 9, 12, 18, and 24
Primary	Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC)	Assessment of change from baseline in target knee function using the WOMAC Osteoarthritis Index. The WOMAC is a proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee including pain, stiffness, and physical functioning of the joints. The response to the questions is in the form of a checked box associated with the response; None, Mild, Moderate, Severe and Extreme.	12 months
Primary	Change in Knee Pain as Assessed by VAS	Assessment of change from baseline in target knee 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.	12 months
Secondary	MRI Assessment of Target Knee	Assessment of knee organ tissues and structure by comparing change in MRI scoring using WORMS and partial MRI Osteoarthritis Knee Score (MOAKS)	12 months
Secondary	PCS of the SF-12 Questionnaire	Evaluation of the change from baseline in physical component score (PCS) of the SF-12v2 questionnaire.	12 months
Secondary	WOMAC Total Score	Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score	24 Months
Secondary	Health Assessment Questionnaire Disability Index	Evaluation of the change from baseline in the disability index of the Health Assessment Questionnaire (HAQ-DI)	12 months