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

• ClinicalTrials.gov Identifier: NCT03203330
• Recruitment Status: Recruiting
• First Posted: June 29, 2017
• Last Update Posted: April 12, 2024
• Sponsor: Kolon TissueGene, Inc.
• Information provided by (Responsible Party): Kolon TissueGene, Inc.

Tracking Information

• First Submitted Date: June 21, 2017
• First Posted Date: June 29, 2017
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: October 30, 2018
• Estimated Primary Completion Date: August 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2018)

• Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC) [ Time Frame: 12 months ]
  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.
• Change in Knee Pain as Assessed by VAS [ Time Frame: 12 months ]
  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.

Original Primary Outcome Measures (submitted: June 26, 2017)

• Knee Function as Assessed by WOMAC [ Time Frame: 12 months ]
  Assessment of improvement from baseline in target knee function using the WOMAC Osteoarthritis Index
• Knee Pain as Assessed by VAS [ Time Frame: 12 months ]
  Assessment of improvement from baseline in target knee pain using the Visual Analog Scale (VAS)

Current Secondary Outcome Measures (submitted: November 29, 2018)

• MRI Assessment of Target Knee [ Time Frame: 12 months ]
  Evaluation of the features of OA, as determined by structural changes of the knee joint, assessed by MRI
• PCS of the SF-12 Questionnaire [ Time Frame: 12 months ]
  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
• WOMAC Total Score [ Time Frame: 24 months ]
  Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score
• Health Assessment Questionnaire Disability Index [ Time Frame: 12 months ]
  Evaluation of the HRQoL as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI)

Original Secondary Outcome Measures (submitted: June 26, 2017)

• International Knee Documentation Committee (IKDC) Scoring of Knee Symptoms, Pain and Function [ Time Frame: 12 and 24 months ]
  Evaluation of target knee symptoms, joint pain, and functionality assessed using the IKDC Subjective knee evaluation
• Change in Joint Space Width [ Time Frame: 12 and 24 months ]
  Evaluation of disease progression in target knee as ascertained by change from baseline in joint space width (JSW) determined using radiography
• PCS of the SF-12 Questionnaire [ Time Frame: 12 and 24 months ]
  Evaluation of the change from baseline in physical component score (PCS) of the SF-12v2 questionnaire.
• Health Assessment Questionnaire Disability Index [ Time Frame: Through 24 months ]
  Evaluation of the change from baseline in the disability index of the Health Assessment Questionnaire (HAQ-DI)

Current Other Pre-specified Outcome Measures (submitted: May 11, 2020)

• Radiography for Structural Change in Knee Joint [ Time Frame: Through 24 months ]
  Evaluate structural changes of the knee joint as determined by radiography (X-ray)
• Efficacy of TG-C with Regard to Knee Function via WOMAC Total Score [ Time Frame: At Months 3, 6, 9 and 18 ]
  Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score
• Efficacy of TG-C with Regard to Knee Function via WOMAC Pain, Function, and Stiffness Scores [ Time Frame: Through 24 months ]
  Evaluate the efficacy of TG-C with regard to knee function via WOMAC® pain, function, and stiffness scores
• Efficacy of TG-C with Regard to Knee Function via VAS Pain Score [ Time Frame: At Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24 ]
  Evaluation of the efficacy of TG-C with regard to knee function via VAS pain score at time points other than Month 12
• OMERACT-OARSI Responder Analysis [ Time Frame: 12 and 24 months ]
  Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria

Original Other Pre-specified Outcome Measures (submitted: June 26, 2017)

• MRI Assessment of Target Knee [ Time Frame: 6, 12 and 24 months ]
  Assessment of knee organ tissues and structure by comparing change in MRI scoring using WORMS and partial MRI Osteoarthritis Knee Score (MOAKS)
• OMERACT-OARSI Responder Analysis [ Time Frame: 12 and 24 months ]
  Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria
• Incidence and Severity of Injection Site Reactions [ Time Frame: Through 24 months ]
  Incidence and severity of swelling, irritation, or other reactions at the site of administration
• Incidence and Severity of Adverse Events (AEs) [ Time Frame: Through 24 months ]
  Incidence and severity of adverse events assess after treatment
• Radiography for Osteophytes [ Time Frame: 12 and 24 months ]
  Radiography for assessment of change from baseline in osteophytes by OARSI criteria
• Changes in Laboratory Tests [ Time Frame: Through 24 months ]
  Changes from baseline in clinical laboratory test results
• Biochemical Biomarker Analysis [ Time Frame: Through 24 months ]
  Assessment of changes from baseline in biochemical biomarkers of knee osteoarthritis
• Frequency of Analgesia Use [ Time Frame: Through 24 months ]
  Evaluation of the frequency and dose of analgesia or anti-inflammatory medication use
• MCS of the SF-12 Questionnaire [ Time Frame: Through 24 months ]
  Evaluation of the change from baseline in the eight domains of the mental component score (MCS) of the SF-12v2 questionnaire

Descriptive Information

• Brief Title: 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
• 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
• Brief 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.
• 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
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-blind

Primary Purpose: Treatment

• Condition: Degenerative Osteoarthritis

Intervention

• Biological: TG-C
  2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1.
  Other Name: TissueGene-C
• Biological: Placebo Control
  2 mL normal saline injection
  Other Name: Normal Saline

Study Arms

• Active Comparator: Active Treatment (TG-C)
  TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection
  Intervention: Biological: TG-C
• Placebo Comparator: Placebo Control (Normal Saline)
  Normal saline, single 2 mL intraarticular injection
  Intervention: Biological: Placebo Control

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 26, 2017): 510
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 30, 2025
• Estimated Primary Completion Date: August 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Aaron Harrison; (910) 399-3238; KTGclinical@tissuegene.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03203330
• Other Study ID Numbers: TGC-12301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Kolon TissueGene, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Kolon TissueGene, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Kolon TissueGene, Inc.
• Verification Date: April 2024