Clinical trial NCT03291470: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Degenerative Osteoarthritis
Keywords: knee
Lead sponsor: Kolon TissueGene, Inc.
Sponsor class: INDUSTRY
First posted: 2017-09-25
Enrollment: 531
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC)
timeFrame: 12 months
measure: Change in Knee Pain as Assessed by VAS
timeFrame: 12 months
Secondary outcomes:
measure: MRI Assessment of Target Knee
timeFrame: 12 months
measure: PCS of the SF-12 Questionnaire
timeFrame: 12 months
measure: WOMAC Total Score
timeFrame: 24 Months
measure: Health Assessment Questionnaire Disability Index
timeFrame: 12 months
Other outcomes:
measure: Radiography for Structural Change in Knee Joint
timeFrame: 24 months
measure: Efficacy of TG-C with Regard to Knee Function via WOMAC Total Score
timeFrame: Week 1, Months 3, 6, 9, 12, 18, and 24
measure: Efficacy of TG-C with Regard to Knee Function via WOMAC Pain, Function, and Stiffness Scores
timeFrame: 24 months
measure: Efficacy of TG-C with Regard to Knee Function via VAS Pain Score
timeFrame: Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24
measure: OMERACT-OARSI Responder Analysis
timeFrame: 12 and 24 months
measure: European Quality of Life-Five Dimensions Questionnaire (EQ-5D-5L)
timeFrame: Baseline and Months 3, 6, 9, 12, 18, and 24
Locations:
city: Tucson
country: United States
facility: Nebojsa Skrepnik
state: Arizona
city: Anaheim
country: United States
facility: Steve Sitar
state: California
city: Beverly Hills
country: United States
facility: Stuart Silverman
state: California
city: Covina
country: United States
facility: Samy Metyas
state: California
city: Huntington Beach
country: United States
facility: Bassil Aish
state: California
city: La Mesa
country: United States
facility: Peter Hanson
state: California
city: San Diego
country: United States
facility: John Beckes
state: California
city: Clearwater
country: United States
facility: Miguel Trevino
state: Florida
city: Doral
country: United States
facility: Jan Hommen
state: Florida
city: West Palm Beach
country: United States
facility: Mira Baron
state: Florida
city: Boise
country: United States
facility: Richard Radnovich
state: Idaho
city: Chicago
country: United States
facility: Thomas Schnitzer
state: Illinois
city: Rochester Hills
country: United States
facility: Nathan Rimmke
state: Michigan
city: Saint Louis
country: United States
facility: Larkin Wadsworth
state: Missouri
city: Las Vegas
country: United States
facility: Duane C Anderson
state: Nevada
city: Brooklyn
country: United States
facility: Igor Grosman
state: New York
city: New York
country: United States
facility: Jonathan Samuels
state: New York
city: Durham
country: United States
facility: John Solic
state: North Carolina
city: Wilmington
country: United States
facility: Jeremy Hoff
state: North Carolina
city: Dayton
country: United States
facility: Priyesh Mehta
state: Ohio
city: Charleston
country: United States
facility: Edward Tavel
state: South Carolina
city: Dallas
country: United States
facility: James Lilly
state: Texas
city: Lewisville
country: United States
facility: Manjoo Sharma
state: Texas
city: Red Oak
country: United States
facility: Haresh Boghara
state: Texas
city: San Antonio
country: United States
facility: Leonel Reyes
state: Texas
city: San Antonio
country: United States
facility: Charles Andrews
state: Texas
city: Spokane
country: United States
facility: David Scott
state: Washington
Study officials:
affiliation: Kolon TissueGene
name: Moon Jong Noh, PhD
role: STUDY_CHAIR
References: