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

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

A randomized, double-blind, placebo-controlled, multi-center, phase 3 study to determine the safety and efficacy 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: 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 KL 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 dosing for subjects who do not enroll in the Long Term Safety study.

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Recruiting
      • Bradly Goodman
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • Jeffrey Davis
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Recruiting
      • Saima Chohan
    • Tucson, Arizona, United States, 85712
      • Recruiting
      • Nebojsa Skrepnik
  • California
    • Apple Valley, California, United States, 92307
      • Recruiting
      • Diraj Karnani
    • Covina, California, United States, 91722
      • Recruiting
      • Dan La
    • La Mesa, California, United States, 91942
      • Recruiting
      • Scott Hacker
    • Napa, California, United States, 94558
      • Recruiting
      • Eric Grigsby
    • San Diego, California, United States, 92108
      • Recruiting
      • Arthur Mabaquiao
    • Santa Monica, California, United States, 90403
      • Recruiting
      • Timothy Davis
    • Whittier, California, United States, 90602
      • Recruiting
      • Tien-I Su
  • District of Columbia
    • Washington, District of Columbia, United States, 20006
      • Recruiting
      • Mehul Desai
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Recruiting
      • Miguel Telleria
    • Daytona Beach, Florida, United States, 32117
      • Recruiting
      • David Billmeier
    • Miami, Florida, United States, 33135
      • Recruiting
      • Mercedes Ponce De Leon
    • Miami, Florida, United States, 33144
      • Recruiting
      • Aurelio Torres-Consuegra
    • Miami, Florida, United States, 33144
      • Recruiting
      • Edgar Gonzalez
    • New Port Richey, Florida, United States, 34652
      • Recruiting
      • Cathy Barnes
    • Oldsmar, Florida, United States, 34677
      • Recruiting
      • Howard Chipman
    • Sunrise, Florida, United States, 33351
      • Recruiting
      • Richard Linn
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Anand Patel
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Recruiting
      • Sandeep Vaid
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Recruiting
      • Manish Jain
    • Chicago, Illinois, United States, 60607
      • Recruiting
      • Dennis Levinson
    • Oak Brook, Illinois, United States, 60523
      • Recruiting
      • Hythem Shadid
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Recruiting
      • Adil Fatakia
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Recruiting
      • Ronald Delanois
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Recruiting
      • Melvin Churchill
  • New York
    • New York, New York, United States, 10022
      • Recruiting
      • Corey Hunter
    • New York, New York, United States, 10075
      • Recruiting
      • Jason Oh
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Recruiting
      • Brett Gilbert
    • Wilmington, North Carolina, United States, 28412
      • Recruiting
      • Jeremy Hoff
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Recruiting
      • Yogesh Mittal
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Recruiting
      • Alan Kivitz
  • South Carolina
    • Columbia, South Carolina, United States, 29206
      • Recruiting
      • Edward Tavel
    • Greenville, South Carolina, United States, 29601
      • Recruiting
      • Eric Loudermilk
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Jason Haslam
  • Texas
    • Bellaire, Texas, United States, 77401
      • Recruiting
      • Daneshvari Solanki
    • Dallas, Texas, United States, 75240
      • Recruiting
      • Amr Morsy
    • DeSoto, Texas, United States, 75115
      • Recruiting
      • Haresh Boghara
    • El Paso, Texas, United States, 79225
      • Recruiting
      • Aldo Maspons
    • Houston, Texas, United States, 77099
      • Recruiting
      • Subodh Bhuchar
    • San Antonio, Texas, United States, 78258
      • Recruiting
      • Brian MacGillivray
  • Utah
    • Draper, Utah, United States, 84020
      • Recruiting
      • David Jack
    • South Ogden, Utah, United States, 84405
      • Recruiting
      • John Hemmersmeier
  • Virginia
    • Charlottesville, Virginia, United States, 22901
      • Recruiting
      • James Clark
    • Danville, Virginia, United States, 24541
      • Recruiting
      • Mark Hermann

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
• Has a score of 0 or >=5 on the cartilage feature of the WORMS at Screening
• 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 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 OA, chondrocalcinosis, gout, hemochromatosis, villonodular synovitis, or synovial chondromatosis
• Severe hip osteoarthritis ipsilateral to the target knee
• Ongoing infection disease including but not limited to HIV, Hepatitis B or C.
• 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

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 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
MRI Assessment of Target Knee	Evaluation of the features of OA, as determined by structural changes of the knee joint, assessed by MRI	12 months
PCS of the SF-12 Questionnaire	Evaluation the Health-Related Quality of Life (HRQoL) as measured by the physical component score (PCS) of the 12-Item Short-Form Health Survey version 2 (SF-12v2®) questionnaire	12 months
WOMAC Total Score	Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score	24 months
Health Assessment Questionnaire Disability Index	Evaluation of the HRQoL as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI)	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiography for Structural Change in Knee Joint	Evaluate structural changes of the knee joint as determined by radiography (X-ray)	Through 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	At Months 3, 6, 9 and 18
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	Through 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	At Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24
OMERACT-OARSI Responder Analysis	Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria	12 and 24 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Mehta S, He T, Bajpayee AG. Recent advances in targeted drug delivery for treatment of osteoarthritis. Curr Opin Rheumatol. 2021 Jan;33(1):94-109. doi: 10.1097/BOR.0000000000000761.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 29, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 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-12301

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