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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

Phase 3
Active, not recruiting
Conditions
Degenerative Osteoarthritis
Interventions
Biological: Placebo Control
Registration Number
NCT03203330
Lead Sponsor
Kolon TissueGene, Inc.
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
535
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active Treatment (TG-C)TG-CTG-C at 3 x 10e7 cells per single 2 mL intraarticular injection
Placebo Control (Normal Saline)Placebo ControlNormal saline, single 2 mL intraarticular injection
Primary Outcome Measures
NameTimeMethod
Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC)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 VAS12 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.

Secondary Outcome Measures
NameTimeMethod
PCS of the SF-12 Questionnaire12 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 Score24 months

Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score

Health Assessment Questionnaire Disability Index12 months

Evaluation of the HRQoL as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI)

MRI Assessment of Target Knee12 months

Evaluation of the features of OA, as determined by structural changes of the knee joint, assessed by MRI

Trial Locations

Locations (46)

Jeffrey Davis

🇺🇸

Birmingham, Alabama, United States

Bradly Goodman

🇺🇸

Birmingham, Alabama, United States

Saima Chohan

🇺🇸

Phoenix, Arizona, United States

Nebojsa Skrepnik

🇺🇸

Tucson, Arizona, United States

Diraj Karnani

🇺🇸

Apple Valley, California, United States

Dan La

🇺🇸

Covina, California, United States

Scott Hacker

🇺🇸

La Mesa, California, United States

Eric Grigsby

🇺🇸

Napa, California, United States

Arthur Mabaquiao

🇺🇸

San Diego, California, United States

Timothy Davis

🇺🇸

Santa Monica, California, United States

Tien-I Su

🇺🇸

Whittier, California, United States

Mehul Desai

🇺🇸

District of columbia, District of Columbia, United States

David Billmeier

🇺🇸

Daytona Beach, Florida, United States

Mercedes Ponce De Leon

🇺🇸

Miami, Florida, United States

Aurelio Torres-Consuegra

🇺🇸

Miami, Florida, United States

Edgar Gonzalez

🇺🇸

Miami, Florida, United States

Cathy Barnes

🇺🇸

New Port Richey, Florida, United States

Howard Chipman

🇺🇸

Oldsmar, Florida, United States

Richard Linn

🇺🇸

Sunrise, Florida, United States

Anand Patel

🇺🇸

Winter Park, Florida, United States

Sandeep Vaid

🇺🇸

Newnan, Georgia, United States

Manish Jain

🇺🇸

Chicago, Illinois, United States

Dennis Levinson

🇺🇸

Chicago, Illinois, United States

Hythem Shadid

🇺🇸

Oak Brook, Illinois, United States

Adil Fatakia

🇺🇸

Marrero, Louisiana, United States

Ronald Delanois

🇺🇸

Baltimore, Maryland, United States

Melvin Churchill

🇺🇸

Lincoln, Nebraska, United States

Corey Hunter

🇺🇸

New York, New York, United States

Jason Oh

🇺🇸

New York, New York, United States

Brett Gilbert

🇺🇸

Durham, North Carolina, United States

Jeremy Hoff

🇺🇸

Wilmington, North Carolina, United States

Yogesh Mittal

🇺🇸

Tulsa, Oklahoma, United States

Alan Kivitz

🇺🇸

Duncansville, Pennsylvania, United States

Edward Tavel

🇺🇸

Columbia, South Carolina, United States

Eric Loudermilk

🇺🇸

Greenville, South Carolina, United States

Harvey Bowles

🇺🇸

Nashville, Tennessee, United States

Daneshvari Solanki

🇺🇸

Bellaire, Texas, United States

Amr Morsy

🇺🇸

Dallas, Texas, United States

Haresh Boghara

🇺🇸

DeSoto, Texas, United States

Aldo Maspons

🇺🇸

El Paso, Texas, United States

Subodh Bhuchar

🇺🇸

Houston, Texas, United States

Brian MacGillivray

🇺🇸

San Antonio, Texas, United States

Angela Krull

🇺🇸

Draper, Utah, United States

John Hemmersmeier

🇺🇸

South Ogden, Utah, United States

James Clark

🇺🇸

Charlottesville, Virginia, United States

Mark Hermann

🇺🇸

Danville, Virginia, United States

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