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

Degenerative Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03203330
• Other study ID #: TGC-12301
• Status: Recruiting
• Phase: Phase 3
• Start date: October 30, 2018
• Est. completion date: August 30, 2025

Study information

• Verified date: April 2024
• Source: Kolon TissueGene, Inc.
• Contact: Aaron Harrison
• Phone: (910) 399-3238
• Email: KTGclinical[@]tissuegene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 510
• Est. completion date: August 30, 2025
• Est. primary completion date: August 30, 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
• 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

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 injection

Locations

Country	Name	City	State
United States	Diraj Karnani	Apple Valley	California
United States	Ronald Delanois	Baltimore	Maryland
United States	Daneshvari Solanki	Bellaire	Texas
United States	Bradly Goodman	Birmingham	Alabama
United States	Jeffrey Davis	Birmingham	Alabama
United States	James Clark	Charlottesville	Virginia
United States	Dennis Levinson	Chicago	Illinois
United States	Manish Jain	Chicago	Illinois
United States	Edward Tavel	Columbia	South Carolina
United States	Miguel Telleria	Coral Gables	Florida
United States	Dan La	Covina	California
United States	Amr Morsy	Dallas	Texas
United States	Mark Hermann	Danville	Virginia
United States	David Billmeier	Daytona Beach	Florida
United States	Haresh Boghara	DeSoto	Texas
United States	David Jack	Draper	Utah
United States	Alan Kivitz	Duncansville	Pennsylvania
United States	Brett Gilbert	Durham	North Carolina
United States	Aldo Maspons	El Paso	Texas
United States	Eric Loudermilk	Greenville	South Carolina
United States	Subodh Bhuchar	Houston	Texas
United States	Scott Hacker	La Mesa	California
United States	Melvin Churchill	Lincoln	Nebraska
United States	Adil Fatakia	Marrero	Louisiana
United States	Aurelio Torres-Consuegra	Miami	Florida
United States	Edgar Gonzalez	Miami	Florida
United States	Mercedes Ponce De Leon	Miami	Florida
United States	Eric Grigsby	Napa	California
United States	Jason Haslam	Nashville	Tennessee
United States	Cathy Barnes	New Port Richey	Florida
United States	Corey Hunter	New York	New York
United States	Jason Oh	New York	New York
United States	Sandeep Vaid	Newnan	Georgia
United States	Hythem Shadid	Oak Brook	Illinois
United States	Howard Chipman	Oldsmar	Florida
United States	Saima Chohan	Phoenix	Arizona
United States	Brian MacGillivray	San Antonio	Texas
United States	Arthur Mabaquiao	San Diego	California
United States	Timothy Davis	Santa Monica	California
United States	John Hemmersmeier	South Ogden	Utah
United States	Richard Linn	Sunrise	Florida
United States	Nebojsa Skrepnik	Tucson	Arizona
United States	Yogesh Mittal	Tulsa	Oklahoma
United States	Mehul Desai	Washington	District of Columbia
United States	Tien-I Su	Whittier	California
United States	Jeremy Hoff	Wilmington	North Carolina
United States	Anand Patel	Winter Park	Florida

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)	Through 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	At Months 3, 6, 9 and 18
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	Through 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	At 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
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	Evaluation of the features of OA, as determined by structural changes of the knee joint, assessed by MRI	12 months
Secondary	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
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 HRQoL as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI)	12 months