Study of Intra-articular Injections vs Placebo in Patients With Pain From Osteoarthritis of the Knee
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Traumeel® / Zeel® Injectable Solution; Placebo
Intervention description: Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one IA injection) on treatment days 1, 8 and 15.; Placebo is an injection of Saline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 287.0
Sex: All
Minimum age: 45 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The aim of this study is to evaluate the effectiveness and safety of a combined Traumeel® /
      Zeel® injection against placebo (saline) in patients with moderate-to-severe pain associated
      with osteoarthritis of the knee.
    

Eligibility criteria:

        Inclusion Criteria (Screening Visit 1):

          1. Osteoarthritis (OA) of the knee by American College of Rheumatology criteria

          2. Men or women between 45-80 years of age.

          3. Have documented diagnosis of primary OA of the target knee based on clinical and
             radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the
             tibial-femoral compartment of the target knee confirmed by standard post-anterior
             weightbearing X-ray of the knee in full extension taken </= 6 months prior to Visit 1.

          4. Currently taking an Nonsteroidal anti-inflammatory drug (NSAID), or acetaminophen on a
             regular basis (4-7 days/ week) over last 2 weeks prior to Visit 1 and has experienced
             amelioration of pain on these medications.

          5. Must have a 50-foot walk test pain score of less than 40 mm on a 100 mm VAS in the
             target knee at screening

          6. Pain in the non-target (contralateral) knee must not be greater than 30 mm on a 100 mm
             VAS on 50-foot walk test, and the target knee must be more symptomatic.

          7. Willingness to stop all OA treatments.

          8. Fully informed of the risks of entering the study and willing to provide written
             consent to enter the study.

          9. Able to understand and be willing to comply with all study requirements, particularly
             the weekly injection regimen for administration of study drug.

         10. Primary complaint is pain immediately following an unassisted 50-foot walk. They must
             show:

               1. moderate to severe pain score in the target knee as demonstrated by 40 - 90 mm
                  recorded on a 100 mm VAS, and

               2. 20 mm increase in pain from their screening visit pain score (a "flare")

               3. pain in the non-target (contralateral) knee must </= 30 mm on a 100 mm VAS

        Exclusion Criteria:

          1. Known hypersensitivity or allergy to any of the components of Traumeel or Zeel

          2. Known hypersensitivity or allergy to acetaminophen.

          3. Has body mass index (BMI) >38 kg/m2.

          4. Avoidance of, or aversion to, nonprescription medications.

          5. Clinical symptoms of meniscal instability or significant valgus/ varus that requires
             corrective osteotomy

          6. Any major injury or surgery to the target knee in the prior 12 months.

          7. One or a combination of the following co-morbidities:

               1. other inflammatory arthropathies, gout or pseudogout within previous 6 months

               2. avascular necrosis

               3. severe bone or joint deformity in target knee

               4. osteonecrosis of either knee

               5. fibromyalgia

               6. pes anserine bursitis

               7. lumbar radiculopathy with referred pain to either knee

               8. neurogenic or vascular claudication

               9. significant anterior knee pain due to diagnosed isolated patella-femoral syndrome
                  in the target knee

              10. target knee joint infection or skin disorder/infection to the area surrounding
                  the knee within previous 6 months

              11. current treatment or treatment of cancer within the previous 2 years (excluding
                  basal cell or squamous cell carcinoma of the skin)

          8. Participated in any experimental drug or device study within the prior one (1) month
             and/or IA injections six (6) months.

          9. Referred pain from other joints

         10. Significantly debilitating concurrent infection(s)

         11. Significant ligamentous instability

         12. Any prior viscosupplementation therapy (in target knee) within 6 months prior to
             Screening

         13. Systemic or IA injection of corticosteroids in any joint within 3 months of enrollment

         14. Therapy with oral hyaluronic acid products, and/or oral pharmaceutical products
             containing glucosamine and/or chondroitin sulphate and/or diacerein

         15. Therapy with opioids within the last 90 days including intra-dermal delivery systems
             (patches)

         16. Therapy with autologous stem cells

         17. Therapy with coumarins such as warfarin, Coumadin; heparin and derivative substances
             including low molecular weight heparin, synthetic pentasaccharide inhibitors of factor
             Xa such as fondaparinux and idraparinux; direct factor Xa inhibitors such as
             rivaroxaban and apixaban; direct thrombin inhibitors such as hirudin, lepirudin,
             bivalirudin, argatroban and dabigatran.

         18. Concomitant inflammatory or other rheumatologic, neurological or cardiovascular
             diseases which could affect the evaluation of knee pain

         19. Ongoing litigation for workers compensation for musculoskeletal injuries or disorders

         20. Use of alcohol of more than 4 drinks per day

         21. Clinically important axial deviation (varus, valgus) greater than 15 degrees

         22. Concomitant severe OA of the hip or other joints, which might interfere with the
             assessments required by the study

         23. Painful knee conditions other than OA (e.g., Paget's disease)

         24. Hemiparesis of lower limbs

         25. Significant planned surgery to lower limbs, which might interfere with the patient's
             ability to comply with study requirements

         26. Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular,
             neurological disease that might interfere with the outcome of the study or the
             patient's ability to comply with study requirements

         27. Presence of infections and/or skin diseases in the area of the injection site such as
             psoriasis

         28. Females who are pregnant or breast-feeding or not using recognized effective
             contraceptive measures. Females of childbearing potential (including those less than
             one year post-menopausal) must agree to maintain reliable birth control throughout the
             study.

         29. Clinically significant abnormal laboratory values.

         30. Patients who are likely to be non-compliant or uncooperative during the study.