Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren/Lawrence Grade 2 or 3 OA of the Knee
Primary Purpose
Degenerative Osteoarthritis
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
TG-C
Placebo Control
Sponsored by
About this trial
This is an interventional treatment trial for Degenerative Osteoarthritis focused on measuring knee
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
- 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.
Sites / Locations
- Hayes WilliamsRecruiting
- John TesserRecruiting
- Nebojsa SkrepnikRecruiting
- George KonisRecruiting
- Steve SitarRecruiting
- Stuart SilvermanRecruiting
- Samy MetyasRecruiting
- Bassil AishRecruiting
- Peter HansonRecruiting
- Natalia Chavez StewartRecruiting
- John BeckesRecruiting
- Miguel TrevinoRecruiting
- Jan HommenRecruiting
- Mira BaronRecruiting
- Richard RadnovichRecruiting
- Thomas SchnitzerRecruiting
- Joel BlockRecruiting
- Nathan RimmkeRecruiting
- Larkin WadsworthRecruiting
- Duane C AndersonRecruiting
- Igor GrosmanRecruiting
- Jonathan SamuelsRecruiting
- John SolicRecruiting
- Rakesh PatelRecruiting
- Jeremy HoffRecruiting
- Priyesh MehtaRecruiting
- Edward TavelRecruiting
- Howsen Kwan
- James LillyRecruiting
- Manjoo SharmaRecruiting
- Haresh BogharaRecruiting
- Leonel ReyesRecruiting
- Charles AndrewsRecruiting
- David ScottRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Active Treatment (TG-C)
Placebo Control (Normal Saline)
Arm Description
TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection
Normal saline, single 2 mL intraarticular injection
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
PCS of the SF-12 Questionnaire
Evaluation of the change from baseline in physical component score (PCS) of the SF-12v2 questionnaire.
Health Assessment Questionnaire Disability Index
Evaluation of the change from baseline in the disability index of the Health Assessment Questionnaire (HAQ-DI)
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)
WOMAC Total Score
Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score
Full Information
NCT ID
NCT03291470
First Posted
September 19, 2017
Last Updated
September 25, 2023
Sponsor
Kolon TissueGene, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03291470
Brief Title
Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren/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 and Safety of TG-C in Subjects With Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 9, 2021 (Actual)
Primary Completion Date
August 30, 2024 (Anticipated)
Study Completion Date
August 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kolon TissueGene, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Degenerative Osteoarthritis
Keywords
knee
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind
Allocation
Randomized
Enrollment
510 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Treatment (TG-C)
Arm Type
Active Comparator
Arm Description
TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection
Arm Title
Placebo Control (Normal Saline)
Arm Type
Placebo Comparator
Arm Description
Normal saline, single 2 mL intraarticular injection
Intervention Type
Biological
Intervention Name(s)
TG-C
Other Intervention Name(s)
TissueGene-C
Intervention Description
2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1
Intervention Type
Biological
Intervention Name(s)
Placebo Control
Other Intervention Name(s)
Normal Saline
Intervention Description
2 mL normal saline intraarticular injection
Primary Outcome Measure Information:
Title
Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC)
Description
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.
Time Frame
12 months
Title
Change in Knee Pain as Assessed by VAS
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
PCS of the SF-12 Questionnaire
Description
Evaluation of the change from baseline in physical component score (PCS) of the SF-12v2 questionnaire.
Time Frame
12 months
Title
Health Assessment Questionnaire Disability Index
Description
Evaluation of the change from baseline in the disability index of the Health Assessment Questionnaire (HAQ-DI)
Time Frame
12 months
Title
MRI Assessment of Target Knee
Description
Assessment of knee organ tissues and structure by comparing change in MRI scoring using WORMS and partial MRI Osteoarthritis Knee Score (MOAKS)
Time Frame
12 months
Title
WOMAC Total Score
Description
Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score
Time Frame
24 Months
Other Pre-specified Outcome Measures:
Title
OMERACT-OARSI Responder Analysis
Description
Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria
Time Frame
12 and 24 months
Title
Radiography for Structural Change in Knee Joint
Description
Evaluate structural changes of the knee joint as determined by radiography (X-ray)
Time Frame
24 months
Title
Efficacy of TG-C with Regard to Knee Function via WOMAC Total Score
Description
Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score
Time Frame
Week 1, Months 3, 6, 9, 12, 18, and 24
Title
Efficacy of TG-C with Regard to Knee Function via WOMAC Pain, Function, and Stiffness Scores
Description
Evaluate the efficacy of TG-C with regard to knee function via WOMAC® pain, function, and stiffness scores
Time Frame
24 months
Title
Efficacy of TG-C with Regard to Knee Function via VAS Pain Score
Description
Evaluation of the efficacy of TG-C with regard to knee function via VAS pain score at time points other than Month 12
Time Frame
Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24
Title
European Quality of Life-Five Dimensions Questionnaire (EQ-5D-5L)
Description
Evaluate health outcomes using the European Quality of Life-Five Dimensions Questionnaire (EQ-5D-5L)
Time Frame
Baseline and Months 3, 6, 9, 12, 18, and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aaron Harrison
Phone
(910) 399-3238
Email
KTGclinical@tissuegene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Moon Jong Noh, PhD
Organizational Affiliation
Kolon TissueGene
Official's Role
Study Chair
Facility Information:
Facility Name
Hayes Williams
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
Individual Site Status
Recruiting
Facility Name
John Tesser
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Individual Site Status
Recruiting
Facility Name
Nebojsa Skrepnik
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Individual Site Status
Recruiting
Facility Name
George Konis
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72211
Country
United States
Individual Site Status
Recruiting
Facility Name
Steve Sitar
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Individual Site Status
Recruiting
Facility Name
Stuart Silverman
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Individual Site Status
Recruiting
Facility Name
Samy Metyas
City
Covina
State/Province
California
ZIP/Postal Code
91722
Country
United States
Individual Site Status
Recruiting
Facility Name
Bassil Aish
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Individual Site Status
Recruiting
Facility Name
Peter Hanson
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Individual Site Status
Recruiting
Facility Name
Natalia Chavez Stewart
City
Riverside
State/Province
California
ZIP/Postal Code
92518
Country
United States
Individual Site Status
Recruiting
Facility Name
John Beckes
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Individual Site Status
Recruiting
Facility Name
Miguel Trevino
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Individual Site Status
Recruiting
Facility Name
Jan Hommen
City
Doral
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Individual Site Status
Recruiting
Facility Name
Mira Baron
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33409
Country
United States
Individual Site Status
Recruiting
Facility Name
Richard Radnovich
City
Boise
State/Province
Idaho
ZIP/Postal Code
83713
Country
United States
Individual Site Status
Recruiting
Facility Name
Thomas Schnitzer
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Name
Joel Block
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Name
Nathan Rimmke
City
Rochester Hills
State/Province
Michigan
ZIP/Postal Code
48307
Country
United States
Individual Site Status
Recruiting
Facility Name
Larkin Wadsworth
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Individual Site Status
Recruiting
Facility Name
Duane C Anderson
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Individual Site Status
Recruiting
Facility Name
Igor Grosman
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11235
Country
United States
Individual Site Status
Recruiting
Facility Name
Jonathan Samuels
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
John Solic
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27704
Country
United States
Individual Site Status
Recruiting
Facility Name
Rakesh Patel
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
Individual Site Status
Recruiting
Facility Name
Jeremy Hoff
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28412
Country
United States
Individual Site Status
Recruiting
Facility Name
Priyesh Mehta
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45432
Country
United States
Individual Site Status
Recruiting
Facility Name
Edward Tavel
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Individual Site Status
Recruiting
Facility Name
Howsen Kwan
City
Carrollton
State/Province
Texas
ZIP/Postal Code
75006
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
James Lilly
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Individual Site Status
Recruiting
Facility Name
Manjoo Sharma
City
Lewisville
State/Province
Texas
ZIP/Postal Code
75057
Country
United States
Individual Site Status
Recruiting
Facility Name
Haresh Boghara
City
Red Oak
State/Province
Texas
ZIP/Postal Code
75154
Country
United States
Individual Site Status
Recruiting
Facility Name
Leonel Reyes
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting
Facility Name
Charles Andrews
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
David Scott
City
Spokane
State/Province
Washington
ZIP/Postal Code
99218
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren/Lawrence Grade 2 or 3 OA of the Knee
We'll reach out to this number within 24 hrs