Inclusion Criteria:
1. The subject must be willing and able to provide written informed consent.
2. Healthy, non-smoking, males and females.
3. Negative Pregnancy test.
4. 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).
5. No clinically significant abnormal findings on blood pressure, heart rate, physical
examination, clinical laboratory tests, or Electrocardiogram (ECG). See details below:
1. Heart Rate (HR) >60 and <100 bpm. 2. Systolic Blood Pressure (BP) >90 and <170 mmHg. 3. Diastolic BP >60 and <80 mmHg. 4. Pulse oximetry ≥95% at room air. 5. Temperature: normal. 6. Laboratory measures within normal range. 7. Liver enzymes <2 x Upper Limit of Normal (ULN)
8. Normal bilirubin. 9. Normal Pain Threshold (PT) / International Normalized Ratio (INR)
10. Estimated Glomerular Filtration Rate (eGFR) >60 ml/min. 11. Normal ECG.
6. Individuals 18 to 80 years old that have knee Osteoarthritis.
7. 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.
8. 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.)
9. 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.)
10. 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.
1. 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).
2. 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.
11. Subjects must have WOMAC and VAS scores of ≥30 and ≥4, respectively at least 2 weeks
prior to enrollment.
12. 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.
13. 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.
Exclusion Criteria:
1. Tibia on femur subluxation greater than 1mm. Varus or valgus number greater than 9°.
2. Intra-articular injection to affected knee within 6 weeks of BMA injection. 3. 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.
4. 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)
5. Subjects with a BMI of >40 and <18 will be excluded.
6. Fever, active infection and ongoing infectious diseases, including HIV and hepatitis. 7. 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).
8. 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.
9. Use of anti-rheumatic medications, including methotrexate and other anti-metabolites.
10. 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.
11. Current chemo or radiation therapy. 12. Current drug or alcohol use disorder. 13. Subjects with h/o noncompliance or serious emotional disabilities, and/or any thought
disorder, etc. will be excluded. 14. 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.)
15. 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.)
16. 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.
17. History of systemic chondrocalcinosis.
18. Vitamin D levels < 30 ng/mL.
19. 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.
20. 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.
21. 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.
22. Subjects may not have popliteal Baker's cyst(s).
