Lyophilized and Micronized Particulate Human Amniotic and Umbilical Cord (TTAX03) for KL Grade 3-4 Knee OA

Inclusion Criteria:

• Able and willing to provide written informed consent
• ≥ 35 and ≤ 85 years of age (until a cap of 30 subjects < 50 years of age is reached, at which point this will convert to ≥ 50 and ≤ 85 years of age)
• Able to reliably complete the KOOS self-administered questionnaire
• Clinical diagnosis of OA of the index knee, with pain onset more than one year prior to screening according to subject recall
• KL grade 3 or 4 in the index knee
• Pain score (KOOS) over the past week ≥ 70 in the index knee at Screening (the index knee will be the more painful knee by ≥ 20 in the case of bilateral disease)
• A ≥ 3 months history of insufficient pain relief from IA hyaluronic acid or a ≥ 3 months history of insufficient pain relief from IA corticosteroids, unless they are medically contraindicated for the subject
• A ≥ 3 months history of insufficient pain relief from other currently recommended treatments, including weight loss and physical therapy

• Any two of the following:

  • Severe knee pain or stiffness that limits everyday activities, including walking, climbing stairs, and getting in and out of chairs. Finding it hard to walk more than a few blocks without significant pain and need to use a cane or walker
  • Moderate or severe knee pain while resting, either day or night
  • Chronic knee inflammation and swelling that does not improve with rest or medications
• BMI ≤ 40 kg/m2
• Adequate bone marrow function (ANC > 1000 × 109 /L, platelets ≥ 100,000 × 109 /L, Hgb ≥ 10 g/dL)
• Adequate hepatic function (AST/ALT ≤ 1.5 × ULN, total bilirubin ≤ 1.2 × ULN)
• Adequate renal function (creatinine ≤ 1.2 × ULN)
• Negative urine test for opioids (including synthetic opioids)
• If female and of child-bearing potential, willingness to use effective birth control during the study.

Exclusion Criteria:

• Cognitive impairment, mental illness, neuroses or untreated depression that would preclude understanding or reliably completing the patient reported outcome measures
• Non-ambulatory, bedridden, or with active fibromyalgia, radiculopathy, painful peripheral neuropathy, vascular insufficiency, hip OA or other joint disease severe enough to prevent assessment of knee pain or causing functional impairment
• Current use of opioid analgesics, or positive urine laboratory test for opiates during the screening period
• Hyaluronic acid, corticosteroid, platelet rich plasma or stem cells IA knee injections within the prior 3 months, oral or intramuscular corticosteroids within the prior 2 months
• Scheduled knee arthroscopy or knee surgery in either knee within 12 weeks from enrollment
• Known or suspected joint infection of either knee
• History of knee ligament surgery in the past 12 months
• Acute injury to the knee in the past 3 months resulting in difficulty walking for more than 24 hours
• History of inflammatory joint diseases, crystalline diseases such as gout or pseudogout, systemic lupus, rheumatoid arthritis, autoimmune disease or Crohn's disease
• Previous repair of a cruciate ligament, osteochondral autograft transfer, mosaicplasty, subchondral surgery (subchondroplasty) or previously diagnosed subchondral insufficiency fracture
• Comorbid conditions that include the following: known other causes of arthritis (infectious arthritis, or psoriatic arthritis), osteomyelitis, cardiopulmonary disease that limits walking more than knee pain, bone metastases or Paget's disease involving the lower extremities.
• Psoriasis or other acute or chronic inflammatory conditions or infection affecting the skin over the index knee
• Symptoms of locking, intermittent block to range of motion or loose body sensation which could indicate meniscal displacement or an intraarticular loose body in the index knee
• Use of anticoagulants (except for ≤ 81 mg of aspirin per day) or a history of any coagulopathy or bleeding disorder, sickle cell disease
• History of substance abuse in the past 2 years
• Prior or current use of systemic immunosuppressive medications (other than corticosteroids for arthritis), chemotherapy, or history of organ transplant (kidney, heart, lung)
• Prior radiation therapy to the index knee
• Prior treatment with CLARIX FLO, NEOX FLO, or injectable birth tissue products for any indication
• Concurrent treatment, or treatment in the past 90 days, with any investigational agent
• Severe concurrent illness which, in the view of the investigator, would interfere with this 52 week study
• Any condition which, in the opinion of the investigator, would make a patient a poor candidate for this study
• Positive blood pregnancy test or known pregnancy