A Study to Evaluate the Safety, and Efficacy of Minimally Manipulated Autologous Bone Marrow Aspirate to Treat Knee Osteoarthritis in Patients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Change from Baseline Visual Analog Score (VAS) at 12 months
研究概览
简要总结
The study is a multicentered, randomized, double-blinded, placebo-controlled study conducted on the unilateral knee of 120 patients. The study compares the effectiveness of an injection of a mesenchymal stem cell preparation from autologous bone marrow aspirate (BMA) to a corticosteroid control for knee osteoarthritis. WOMAC, VAS pain scores, and MRI will be used for assessment. The study will be conducted at 3 sites in the United States.
详细描述
Osteoarthritis (OA) is the most common form of arthritis in the knee that affects millions of adults throughout the world and is the leading cause of disability. It is a degenerative type of arthritis that occurs most often in patients, as the cartilage in the knee joint gradually wears away. As the cartilage wears away, it becomes frayed and rough, and the protective space between the bones decreases. This can result in bone rubbing on bone and produce painful bone spurs. The patient experiences pain that worsens over time.
Although current surgical therapeutic procedures to cartilage repair are clinically useful, they cannot restore a normal articular surface, and in many cases, resulted in the growth of inferior quality fibrocartilage. Therefore, techniques and practices have been developed to collect minimally manipulated bone marrow aspirate (BMA), that contains Bone Marrow Derived Mesenchymal Stem Cells (BMDMSCs) and other endogenous acellular components, from knee OA patients for autologous transplantation in the treatment of their knee OA.
Participants will be randomized to study arms to receive a BMA injection to the intra-articular knee, subchondral knee, both intra-articular and subchondral knee, or to receive a corticosteroid injection to the knee. A corticosteroid injection is currently the standard of care for osteoarthritis patients having knee pain. All participants will undergo a procedure. Participants will be blinded as to whether they receive a BMA injection or a corticosteroid injection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Corticosteroid as control both participant and investigator blinded.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject must be willing and able to provide written informed consent.
- •Healthy, non-smoking, males and females.
- •Negative Pregnancy test.
- •Body weight > 45 kg and Body Mass Index (BMI) between 18 and 40 kg/m2 (i.e., subjects with a BMI >40 and <18 will be excluded).
- •No clinically significant abnormal findings on blood pressure, heart rate, physical examination, clinical laboratory tests, or Electrocardiogram (ECG). See details below:
- •Heart Rate (HR) >60 and <100 bpm
- •Systolic Blood Pressure (BP) >90 and <170 mmHg
- •Diastolic BP >60 and <80 mmHg
- •Pulse oximetry ≥95% at room air
- •Temperature: normal
- •Laboratory measures within normal range
- •Liver enzymes <2 x Upper Limit of Normal (ULN)
- •Normal bilirubin
- •Normal Pain Threshold (PT) / International Normalized Ratio (INR)
- •Estimated Glomerular Filtration Rate (eGFR) >60 ml/min
- •Normal ECG.
- •Individuals 18 to 80 years old that have knee Osteoarthritis.
- •X-rays that demonstrate OA with the Kellgren-Lawrence grading scale of 2, 3 or 4 in at least one compartment of the knee either or both knees. Only subjects that have a single symptomatic knee will be enrolled.
- •No significant Medial Collateral Ligament (MCL) or Lateral Collateral Ligament (LCL) tear or laxity. (A significant LCL and MCL laxity or tear would be determined on clinical exam if there is no endpoint on valgus or Varus stress physical exam. Upon review of the MRI, NGRM will only treat subjects with no grade 2 or grade 3 ligamentous sprains [LCL, MCL, Anterior Cruciate Ligament (ACL), Posterior Cruciate Ligament (PCL)]. Next Generation Regenerative Medicine (NGRM) will treat subjects with degenerative meniscal changes in tears but no acute or large bucket handle tears.)
- •No significant meniscal tear. (i.e. bucket handle) (A positive McMurrays test on clinical exam indicates a significant meniscal tear. The subjects will also be getting a baseline MRI that will help delineate any further ligament injuries that may disqualify a subject.)
- •Subjects who have had the benefit of standard of care (SOC) treatment (activity modification, weight loss, physical therapy, anti-inflammatory medications, or injection therapy) before receiving experimental therapy. However, subjects cannot have had the benefit of standard of care treatment at less than 3 months before receiving experimental therapy. Enroll subjects who have demonstrated failure or are intolerant to SOC treatment. The time frame prior to screening when failure of conservative treatment would have occurred will be one year of symptoms and failure of conservative treatment which includes physical therapy, nonsteroidal anti-inflammatory medicine, cortizone injections, or hyaluronic acid injections.
- •Treatment failure is indicated by Subjects having symptoms of knee pain, swelling, and trouble with activities for at least 4 to 6 weeks. Subjects would only be enrolled if they fail conservative treatment. Usually physical therapy is administered initially for 6 weeks along with an NSAID medication. If that fails, which means that pain and swelling and disability continue, then injection therapy with corticosteroid or hyaluronic acid (HA) is given. Usually the injection is followed up in 6 to 8 weeks post-injection. If that fails, then Orthobiologics will be discussed (at about 4 to 6 months after treatment).
- •The subject must fail at least two conservative treatments, which could include physical therapy and NSAIDs, or physical therapy and injections, or NSAIDs and injections.
- •Subjects must have WOMAC and VAS scores of ≥30 and ≥4, respectively at least 2 weeks prior to enrollment.
- •Male and female subjects of reproductive potential must agree to refrain from sexual activity or use effective birth control for a duration of one week before and three months after initiation of treatment with either active treatment modality.
- •Subjects with basal cell, in situ carcinoma, or remote history (i.e., > 3 years ago) history of low-grade cancers (e.g., breast) that were effectively treated may be included.
排除标准
- •Tibia on femur subluxation greater than 1mm. Varus or valgus number greater than 9°.
- •Intra-articular injection to affected knee within 6 weeks of BMA injection
- •Subjects who have had recent administration of intra- articular injection (e.g. corticosteroid, viscosupplement, platelet-rich plasma (PRP), or any other stem cell therapy) within the last 3 months prior to the experimental therapy.
- •Subjects who have had recent systemic (oral (PO), intravenous (IV) and/or intramuscular (IM) within 6 weeks of treatment) administration of corticosteroids; including subjects who are likely to need or who are currently on systemic steroids (e.g., asthma)
- •Subjects with a BMI of >40 and <18 will be excluded.
- •Fever, active infection and ongoing infectious diseases, including HIV and hepatitis
- •Clinically significant diabetes (HGB A1C >7%), cardiovascular (stable cardiovascular (CV) disease as indicated by treating cardiologist within 30 days of enrollment and/or an ejection fraction of <55%), hepatic (Pugh score of Class A or less than 6), or renal disease (Stage 1 or more severe).
- •Malignancy of the blood such as leukemia or lymphoma or those malignancies which are not > 5 years post treatment including prostate cancer, breast cancer, thyroid cancer, kidney cancer or lung cancer. Subjects with an active malignancy, or subjects with a history of any malignancy (e.g., including in situ, basal cell, etc.) will be excluded.
- •Use of anti-rheumatic medications, including methotrexate and other anti-metabolites.
- •Patients that are chronically taking Plavix, Coumadin and other anticoagulants for stroke/myocardial infarction/thromboembolic phenomena prevention, and/or Pradaxa, Xarelto, Mylanta, Fish Oil, Elmiron, Cipro, Levaquin, Quinolones, Ibuprofen, aspirin, Naproxen, CBD oil, Turmeric, or Meloxicam.
- •Current chemo or radiation therapy
- •Current drug or alcohol use disorder
- •Subjects with h/o noncompliance or serious emotional disabilities, and/or any thought disorder, etc. will be excluded
- •History of severe anemia or bleeding disorders (infectious arthritis, hemophilic arthropathy, Charcot's knee) (Anemia for the study is defined as Hgb 12 g/dL.)
- •History of severe metabolic bone disease (osteoporosis, osteomalacia, rickets, osteitis fibrosa cystica, Paget's disease of bone) (Metabolic bone disease is osteoporosis diagnosed by DEXA scan, Leukemia, aplastic anemia or bone Metastasis.)
- •Pregnant or currently breast-feeding. Males and females of reproductive potential will refrain from sexual activity or use effective birth control for up to 90 days following product administration.
- •History of systemic chondrocalcinosis.
- •Vitamin D levels < 30 ng/mL.
- •Subjects who are unwilling to forgo pain medication during and for a 2 weeks before clinical assessments will be excluded to decrease the potential for confounding of the efficacy assessments.
- •Subjects with claudication and vascular disorders (such as varicose veins or peripheral arterial disease), neurological disorders or other disabilities aside from osteoarthritis that may affect ambulation.
- •Physical Exam findings include severe peripheral vascular disease, deep vain thrombosis (DVT), heart murmur, clubbing, open wounds, and other specific knee findings including significant varus or valgus deformity or subluxation of the femoral - tibial joint space, patellar tracking issues, trendelenburg gait or extremity weakness or significant peripheral neuropathy.
- •Subjects may not have popliteal Baker's cyst(s).
研究组 & 干预措施
Intra-articular injection with Bone Marrow Derived Mesenchymal Stem Cells (MSCs)
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single intra-articular injection of NGRM-001 on treatment day.
干预措施: Bone Marrow Derived MSCs (Biological)
Intra-articular injection with Bone Marrow Derived Mesenchymal Stem Cells (MSCs)
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single intra-articular injection of NGRM-001 on treatment day.
干预措施: Bone Marrow Aspirate (Device)
Subchondral injection with Bone Marrow Derived MSCs
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single subchondral injection of NGRM-001 on treatment day.
干预措施: Bone Marrow Derived MSCs (Biological)
Subchondral injection with Bone Marrow Derived MSCs
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single subchondral injection of NGRM-001 on treatment day.
干预措施: Bone Marrow Aspirate (Device)
Combined Intra-articular and Subchondral injection with Bone Marrow Derived MSCs
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single combined intra-articular and subchondral injection of NGRM-001 on treatment day.
干预措施: Bone Marrow Derived MSCs (Biological)
Combined Intra-articular and Subchondral injection with Bone Marrow Derived MSCs
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single combined intra-articular and subchondral injection of NGRM-001 on treatment day.
干预措施: Bone Marrow Aspirate (Device)
Corticosteroid injection
Subjects in the corticosteroid group will undergo a mock bone marrow aspirate procedure. Participants will receive a single intra-articular injection of corticosteroid on treatment day.
干预措施: Corticosteroid (Drug)
Corticosteroid injection
Subjects in the corticosteroid group will undergo a mock bone marrow aspirate procedure. Participants will receive a single intra-articular injection of corticosteroid on treatment day.
干预措施: Bone Marrow Aspirate (Device)
结局指标
主要结局
Change from Baseline Visual Analog Score (VAS) at 12 months
时间窗: 12 months
The pain VAS is a unidimensional scale of pain that is widely used and well validated in diverse groups of adult patients. The horizontal scale will be anchored by "no pain" (0) with "worst imaginable pain" (10) being at the opposite extreme. The minimum clinically important difference (MCID) for this measure is VAS ≥ 2
Change from Baseline Western Ontario McMaster University Osteoarthritis Index (WOMAC) at 12 months
时间窗: 12 months
The Western Ontario and McMaster Universities Osteoarthritis Index is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The minimum clinically important difference (MCID) for this parameter is ≥ 10.
Change from Baseline Visual Analog Score (VAS) at 3 months
时间窗: 3 months
The pain VAS is a unidimensional scale of pain that is widely used and well validated in diverse groups of adult patients. The horizontal scale will be anchored by "no pain" (0) with "worst imaginable pain" (10) being at the opposite extreme. The minimum clinically important difference (MCID) for this measure is VAS ≥ 2
Change from Baseline Western Ontario McMaster University Osteoarthritis Index (WOMAC) at 3 months
时间窗: 3 months
The Western Ontario and McMaster Universities Osteoarthritis Index is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The minimum clinically important difference (MCID) for this parameter is ≥ 10.
Change from Baseline Visual Analog Score (VAS) at 6 months
时间窗: 6 months
The pain VAS is a unidimensional scale of pain that is widely used and well validated in diverse groups of adult patients. The horizontal scale will be anchored by "no pain" (0) with "worst imaginable pain" (10) being at the opposite extreme. The minimum clinically important difference (MCID) for this measure is VAS ≥ 2
Magnetic Resonance Imaging (MRI) Evaluation
时间窗: Baseline and 12 months
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body in both health and disease. MRI scanners use strong magnetic fields, radio waves, and field gradients to generate images of the inside of the body.
Change from Baseline Western Ontario McMaster University Osteoarthritis Index (WOMAC) at 6 months
时间窗: 6 months
The Western Ontario and McMaster Universities Osteoarthritis Index is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The minimum clinically important difference (MCID) for this parameter is ≥ 10.
次要结局
- Change from baseline measure of Fall Risk Functional Testing at 3 months(3 months)
- Change from baseline measure of Obesity Functional Testing at 12 months(12 months)
- Change from baseline measure of Fall Risk Functional Testing at 6 months(6 months)
- Change from baseline measure of Frailty Functional Testing at 3 months(3 months)
- Change from baseline measure of Joint Specific Range of Motion Functional Testing at 12 months.(12 months)
- Change from baseline measure of Fall Risk Functional Testing at 12 months(12 months)
- Change from baseline measure of Frailty Functional Testing at 12 months(12 months)
- Change from baseline measure of Joint Specific Range of Motion Functional Testing at 3 months.(3 months)
- Change from baseline measure of Joint Specific Range of Motion Functional Testing at 6 months.(6 months)
- Change from baseline measure of Obesity Functional Testing at 6 months(6 months)
- Change from baseline measure of Frailty Functional Testing at 6 months(6 months)
- Change from baseline measure of Obesity Functional Testing at 3 months(3 months)