Randomized, Prospective, Double Blind, Multi-Center, Phase 3 Pivotal Clinical Trial to Compare Efficacy and Safety of CARTISTEM® and Surgical Comparator in Subjects With Knee Cartilage Lesions and Osteoarthritis
To establish the efficacy and safety of CARTISTEM®, a combination product composed of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) formulated with a cross-linked sodium hyaluronate (HA) hydrogel, CARTISTEM® compared to the surgical comparator of debridement in Subjects with knee cartilage lesions and osteoarthritis. This trial is intended to provide evidence of the superiority of CARTISTEM® to reduce knee pain and improve knee function compared to debridement for Subjects with knee cartilage lesions and osteoarthritis at 2-years post-treatment. Additionally, this trial is intended to intended to explore whether CARTISTEM® may have disease-modifying effects on osteoarthritis progression through the use of semi-quantitative MRI assessment.
• Age ≥ 18 and ≤ 75 years old.
• Knee Osteoarthritis diagnosed in the index knee according to the clinical definition of American College of Rheumatology (ACR) guidelines at screening.
• Failed conservative knee osteoarthritis treatment for at least 3 months prior to consent (weight reduction, physical therapy, injections, pain medications, etc.).
• Kellgren-Lawrence (KL) in the index knee of grade 2 to 3 as determined by independent radiologist review of study X-Ray.
• Clinically relevant femoral cartilage defects classified using modified Outerbridge Grade 3 or 4 in index knee with combined lesion area ≥ 2 cm2 and ≤ 9 cm2 and at least a single femoral lesion ≥ 2 cm2 as determined by independent radiologist review of study MRI.
• Body Mass Index (BMI) ≤ 35 kg / m2 .
• VAS PAIN index knee score ≥ 40 to ≤ 90 based on 100-point scale at screening.
• VAS PAIN contralateral knee score ≤ 30 based on 100-point scale at screening.
• WOMAC® FUNCTION index knee mean score ≥ 25 to ≤ 90 based on 100-point scale at screening.
⁃ WOMAC® Pain index knee mean score ≥ 40 to ≤ 90 based on 100-point VAS (visual analogue scale) at screening.
⁃ Subjects must be willing to abstain from treatments in the index knee from the time the informed consent is signed until after the last study follow up visit.
⁃ Subjects must be willing to discontinue analgesics except:
∙ Rescue medication (acetaminophen) allowed for break-through pain throughout the study.
‣ Subjects must be willing to discontinue use of all pain medications at least 48 hours prior to baseline assessment and each follow up visit.
‣ Limited postoperative NSAID use is permissible per IND clinical guidance and site manual, provided washout before scheduled efficacy assessments.
‣ Post operative narcotics.
⁃ Subjects with stage 3 hypertension (systolic ≥ 180 mm Hg and diastolic ≥ 120 mmHg) must have blood pressure (BP) controlled prior to surgical procedure.
⁃ Subject's central lab results are within normal ranges or deemed as not clinically significant by investigator for CARTISTEM® treatment or surgical comparator.
⁃ Female Subjects of childbearing potential must agree to practice adequate methods of birth control to prevent pregnancy during the study.
⁃ Subjects must be able to comply fully with the rehabilitation requirements.
⁃ Subjects must be able to understand and comply with the requirements of the study.
⁃ Subjects must voluntarily provide written informed consent.