Knee Cartilage Defects
Conditions
Keywords
symptomatic knee cartilage defects, knee cartilage, cartilage repair, osteoarthritis
Brief summary
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.
Interventions
BIOLOGICALCARTISTEM® + Debridement
CARTISTEM® + Debridement CARTISTEM® consists of approximately 7.5 x 106 hUCB-MSCs (human umbilical cord blood-derived mesenchymal stem/stromal cells) suspended in 1.5 ml medium in one vial, and 60 mg sodium hyaluronate provided as a lyophilized powder in a separate vial. A viscous and malleable gel matrix is formed by mixing hUCB-MSCs (main component) and 60mg of sodium hyaluronate at a 4% concentration (excipient).
PROCEDUREDebridement
Debridement of unstable cartilage in and around cartilage lesion(s) in the knee.
Sponsors
Medipost, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 and ≤ 75 years old. 2. Knee Osteoarthritis diagnosed in the index knee according to the clinical definition of American College of Rheumatology (ACR) guidelines at screening. 3. Failed conservative knee osteoarthritis treatment for at least 3 months prior to consent (weight reduction, physical therapy, injections, pain medications, etc.). 4. Kellgren-Lawrence (KL) in the index knee of grade 2 to 3 as determined by independent radiologist review of study X-Ray. 5. 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. 6. Body Mass Index (BMI) ≤ 35 kg / m2 . 7. VAS PAIN index knee score ≥ 40 to ≤ 90 based on 100-point scale at screening. 8. VAS PAIN contralateral knee score ≤ 30 based on 100-point scale at screening. 9. WOMAC® FUNCTION index knee mean score ≥ 25 to ≤ 90 based on 100-point scale at screening. 10. WOMAC® Pain index knee mean score ≥ 40 to ≤ 90 based on 100-point VAS (visual analogue scale) at screening. 11. 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. 12. 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. 13. Subjects with stage 3 hypertension (systolic ≥ 180 mm Hg and diastolic ≥ 120 mmHg) must have blood pressure (BP) controlled prior to surgical procedure. 14. Subject's central lab results are within normal ranges or deemed as not clinically significant by investigator for CARTISTEM® treatment or surgical comparator. 15. Female Subjects of childbearing potential must agree to practice adequate methods of birth control to prevent pregnancy during the study. 16. Subjects must be able to comply fully with the rehabilitation requirements. 17. Subjects must be able to understand and comply with the requirements of the study. 18. Subjects must voluntarily provide written informed consent.
Exclusion criteria
1. Subject received an IA injection of Hyaluronic Acid (HA), Platelet Rich Plasma (PRP), Bone Marrow Aspirate / Concentrate (BMA / BMAC), long-acting / conventional steroid, or investigational drug in either knee within 3 months of signing informed consent. Note: injections of the contralateral knee are allowed during the trial. 2. Bone marrow lesion (BML) grade 3 on femur, tibia, or patella except at femoral lesion area (BML grade 3 allowed) in index knee as determined by independent radiologist review of study MRI. 3. KL index knee grade 0, 1 or 4 as determined by independent radiologist review of study X-Ray. 4. KL Contralateral knee severity grade 4 as determined by independent radiologist review of study X-Ray. 5. Anatomical axis varus or valgus malalignment ≥ 6° in either knee as determined by independent radiologist. 6. Joint ligament instability in index knee ≥ Grade 3 or ligament instability that would require surgical intervention as determined by investigator or designee. 7. Complete meniscal deficiency, meniscal root tears and / or severe meniscal extrusion as determined by independent radiologist. 8. Kissing bipolar lesions (tibial or patellar) Outerbridge 4 exceeding 25% of the femoral lesion area in size and/or penetrating through the subchondral bone as determined by independent radiologist. 9. Surgery of the index knee joint within 6 months of signing the informed consent. Investigator confirms that Subject has recovered from any prior surgical intervention to enable treatment within this study protocol. No radiation therapy of the index knee as determined by documented medical history. 10. Chronic inflammatory articular diseases such as rheumatoid arthritis, gout, pseudogout, gouty arthritis, or fibromyalgia as determined by documented medical history. 11. Bone disorders of index knee: osteonecrosis including avascular necrosis (AVN); Osteochondritis dissecans (OCD); Spontaneous Osteonecrosis of the Knee (SONK); Subchondral Insufficiency Fracture (SIF); Subchondral / intraosseous bone cyst \>4mm at femoral treatment location, bone tumors, bone contusion or stress fracture, pathologic fracture, and other bone exclusionary findings as determined by independent radiologist review of study MRI or X-ray. 12. Joint disorders of the index knee including infection, osteomyelitis, soft tissue tumors, and bone marrow infiltration as determined by independent radiologist review of study MRI or X-ray. 13. Diseases or disorders including Paget's disease, ochronosis, acromegaly, haemochromatosis, Wilson's disease, genetic disease (hyperkinesia, etc.), or genetic collagen disorder as determined by documented medical history. 14. Vascular or neurological disorders of the lower extremities as determined by documented medical history. Note: Varicose veins are not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale (VAS) Pain Score | From enrollment to end of follow-up at 24 months | Change from Baseline Visual Analog Scale (VAS) Pain score (0-100 point scale, 0 being no pain at one end and 100 being the worst imaginable pain at the other) in index knee comparing CARTISTEM® to surgical control at 24-months post-treatment. |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Function score | From start of treatment to the end of follow-up at 24 months | Change from Baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Function score (0-100 point scale, 0 being the best functioning and 100 being the worst functioning) in index knee comparing CARTISTEM® to surgical control at 24-months post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score | enrollment to follow-up at 24 months. | Change in modified MOCART score in Index knee comparing CARTISTEM® to surgical control at 24-months post-treatment. |
| Change in MRI Osteoarthritis Knee Score (MOAKS) cartilage morphology | enrollment to follow up at 24 months | Change in MOAKS cartilage morphology with delta sum score - extent of cartilage damage score in Index knee comparing CARTISTEM® to surgical control at 24-months post-treatment. |
Countries
United States
Contacts
CONTACTAdrian Orr, VP Clinical Development
CONTACTLuis Toro, Medical Monitor for IQVIA, MD
Outcome results
None listed