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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Degenerative Osteoarthritis
• Intervention / Treatment: Biological: TG-C; Biological: Placebo Control

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 511
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Aaron Harrison; Phone Number: (910) 399-3238; Email: KTGclinical@tissuegene.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Nebojsa Skrepnik
  • California
    • Anaheim, California, United States, 92801
      • Steve Sitar
    • Beverly Hills, California, United States, 90211
      • Stuart Silverman
    • Covina, California, United States, 91722
      • Samy Metyas
    • Huntington Beach, California, United States, 92647
      • Bassil Aish
    • La Mesa, California, United States, 91942
      • Peter Hanson
    • San Diego, California, United States, 92120
      • John Beckes
  • Florida
    • Clearwater, Florida, United States, 33756
      • Miguel Trevino
    • Doral, Florida, United States, 33126
      • Jan Hommen
    • West Palm Beach, Florida, United States, 33409
      • Mira Baron
  • Idaho
    • Boise, Idaho, United States, 83713
      • Richard Radnovich
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Thomas Schnitzer
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Nathan Rimmke
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Larkin Wadsworth
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Duane C Anderson
  • New York
    • Brooklyn, New York, United States, 11235
      • Igor Grosman
    • New York, New York, United States, 10016
      • Jonathan Samuels
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • John Solic
    • Wilmington, North Carolina, United States, 28412
      • Jeremy Hoff
  • Ohio
    • Dayton, Ohio, United States, 45432
      • Priyesh Mehta
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Edward Tavel
  • Texas
    • Dallas, Texas, United States, 75230
      • James Lilly
    • Lewisville, Texas, United States, 75057
      • Manjoo Sharma
    • Red Oak, Texas, United States, 75154
      • Haresh Boghara
    • San Antonio, Texas, United States, 78215
      • Leonel Reyes
    • San Antonio, Texas, United States, 78229
      • Charles Andrews
  • Washington
    • Spokane, Washington, United States, 99218
      • David Scott

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Treatment (TG-C); TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection	Biological: TG-C; 2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1; Other Names: TissueGene-C
Placebo Comparator: Placebo Control (Normal Saline); Normal saline, single 2 mL intraarticular injection	Biological: Placebo Control; 2 mL normal saline intraarticular injection; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCS of the SF-12 Questionnaire	Evaluation of the change from baseline in physical component score (PCS) of the SF-12v2 questionnaire.	12 months
Health Assessment Questionnaire Disability Index	Evaluation of the change from baseline in the disability index of the Health Assessment Questionnaire (HAQ-DI)	12 months
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
WOMAC Total Score	Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score	24 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
OMERACT-OARSI Responder Analysis	Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria	12 and 24 months
Radiography for Structural Change in Knee Joint	Evaluate structural changes of the knee joint as determined by radiography (X-ray)	24 months
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
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
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
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

Collaborators and Investigators

• Sponsor: Kolon TissueGene, Inc.
• Investigators: Study Chair: Moon Jong Noh, PhD, Kolon TissueGene

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Actual): March 6, 2024
• Study Completion (Estimated): March 6, 2026

Study Registration Dates

• First Submitted: September 19, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: knee
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: TGC-15302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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