Clinical trial NCT03203330: 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
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: 2017-06-29
Enrollment: 535
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 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.

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

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: Through 24 months
measure: Efficacy of TG-C with Regard to Knee Function via WOMAC Total Score
timeFrame: At Months 3, 6, 9 and 18
measure: Efficacy of TG-C with Regard to Knee Function via WOMAC Pain, Function, and Stiffness Scores
timeFrame: Through 24 months
measure: Efficacy of TG-C with Regard to Knee Function via VAS Pain Score
timeFrame: At Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24
measure: OMERACT-OARSI Responder Analysis
timeFrame: 12 and 24 months
Locations:
city: Birmingham
country: United States
facility: Jeffrey Davis
state: Alabama
city: Birmingham
country: United States
facility: Bradly Goodman
state: Alabama
city: Phoenix
country: United States
facility: Saima Chohan
state: Arizona
city: Tucson
country: United States
facility: Nebojsa Skrepnik
state: Arizona
city: Apple Valley
country: United States
facility: Diraj Karnani
state: California
city: Covina
country: United States
facility: Dan La
state: California
city: La Mesa
country: United States
facility: Scott Hacker
state: California
city: Napa
country: United States
facility: Eric Grigsby
state: California
city: San Diego
country: United States
facility: Arthur Mabaquiao
state: California
city: Santa Monica
country: United States
facility: Timothy Davis
state: California
city: Whittier
country: United States
facility: Tien-I Su
state: California
city: District of columbia
country: United States
facility: Mehul Desai
state: District of Columbia
city: Daytona Beach
country: United States
facility: David Billmeier
state: Florida
city: Miami
country: United States
facility: Mercedes Ponce De Leon
state: Florida
city: Miami
country: United States
facility: Aurelio Torres-Consuegra
state: Florida
city: Miami
country: United States
facility: Edgar Gonzalez
state: Florida
city: New Port Richey
country: United States
facility: Cathy Barnes
state: Florida
city: Oldsmar
country: United States
facility: Howard Chipman
state: Florida
city: Sunrise
country: United States
facility: Richard Linn
state: Florida
city: Winter Park
country: United States
facility: Anand Patel
state: Florida
city: Newnan
country: United States
facility: Sandeep Vaid
state: Georgia
city: Chicago
country: United States
facility: Dennis Levinson
state: Illinois
city: Chicago
country: United States
facility: Manish Jain
state: Illinois
city: Oak Brook
country: United States
facility: Hythem Shadid
state: Illinois
city: Marrero
country: United States
facility: Adil Fatakia
state: Louisiana
city: Baltimore
country: United States
facility: Ronald Delanois
state: Maryland
city: Lincoln
country: United States
facility: Melvin Churchill
state: Nebraska
city: New York
country: United States
facility: Corey Hunter
state: New York
city: New York
country: United States
facility: Jason Oh
state: New York
city: Durham
country: United States
facility: Brett Gilbert
state: North Carolina
city: Wilmington
country: United States
facility: Jeremy Hoff
state: North Carolina
city: Tulsa
country: United States
facility: Yogesh Mittal
state: Oklahoma
city: Duncansville
country: United States
facility: Alan Kivitz
state: Pennsylvania
city: Columbia
country: United States
facility: Edward Tavel
state: South Carolina
city: Greenville
country: United States
facility: Eric Loudermilk
state: South Carolina
city: Nashville
country: United States
facility: Harvey Bowles
state: Tennessee
city: Bellaire
country: United States
facility: Daneshvari Solanki
state: Texas
city: Dallas
country: United States
facility: Amr Morsy
state: Texas
city: DeSoto
country: United States
facility: Haresh Boghara
state: Texas
city: El Paso
country: United States
facility: Aldo Maspons
state: Texas
city: Houston
country: United States
facility: Subodh Bhuchar
state: Texas
city: San Antonio
country: United States
facility: Brian MacGillivray
state: Texas
city: Draper
country: United States
facility: Angela Krull
state: Utah
city: South Ogden
country: United States
facility: John Hemmersmeier
state: Utah
city: Charlottesville
country: United States
facility: James Clark
state: Virginia
city: Danville
country: United States
facility: Mark Hermann
state: Virginia
Study officials:
affiliation: Kolon TissueGene, Inc.
name: Moon Jong Noh, PhD
role: STUDY_CHAIR
References:
citation: 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.