Clinical trial: A Phase 1, Double-Blind, Randomized, Single Dose Escalation Safety Study of Intra-articular OP-1 in Subjects With Osteoarthritis of the Knee (NCT00456157)

Eligibility criteria:
Inclusion Criteria:

          -  Ambulatory subjects with OA of the knee with symptoms for at least 6 months and pain
             on the majority of days in the last 30 days. Symptoms must include knee joint pain,
             and may include crepitus, swelling and/or effusion of the knee. In subjects with
             bilateral knee OA, the more symptomatic knee is the index knee. Subjects may be taking
             NSAIDs, analgesics and/or undergoing physical therapy.

          -  Age > 40 years

          -  Radiographic evidence on posteroanterior (PA) and lateral standing, flexed x-rays of
             at least one osteophyte.

          -  Subjects must be willing to abstain from other intraarticular treatments of the knee
             or any surgery for 12 weeks on study.

          -  Ability to comply with the study and give informed consent.

          -  Subjects must be willing to abstain from NSAIDs or analgesic medications (except for
             acetaminophen) for 48 hours prior to assessments, at screening, day 1 and week 4, 8,
             12, and 24 visits.

        Exclusion Criteria:

          -  Concurrent medical or arthritic conditions which could interfere with evaluation of
             the index knee joint including fibromyalgia.

          -  Subject has received arthroscopic or open surgery to the index joint within 6 months
             of study start

          -  The presence of surgical hardware or other foreign body in the index joint

          -  Corticosteroid, hyaluronic acid or other intraarticular injection within 3 months of
             study start

          -  Use of chondroitin and/or glucosamine within 4 weeks prior to study start

          -  History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing
             spondylitis, lymphoma, arthritis associated with inflammatory bowel disease,
             sarcoidosis or amyloidosis

          -  Clinical signs and symptoms of active knee infection or crystal disease

          -  Clinically significant cardiac disease, consult study Medical Monitor

          -  Have an increased predisposition for the development of infections

          -  History of malignancy, with the exception of resected basal cell carcinoma, squamous
             cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ.

          -  More significant pain from the back or the hip than the knee

          -  Skin breakdown at the knee where the injection would take place

          -  Planned knee replacement during the study period

          -  For subjects undergoing MRI, the presence of contraindications to having an MRI at the
             specific imaging facility.

          -  For subjects undergoing MRI, an estimated Glomerular Filtration Rate (eGFR) of <45
             mL/min calculated using the Cockcroft-Gault estimate for eGFR as follows:

        eGFR = (140-age [yrs]) X weight [kg] / serum creatinine [mg/dL] X 72 (X 0.85 for women)

          -  For subjects undergoing MRI, known allergy to gadolinium contrast material

          -  Has known or clinically suspected infection with human immunodeficiency virus (HIV),
             hepatitis C or B viruses

          -  Has participated within 30 days or will participate concurrently in another
             investigational drug or vaccine study

          -  Has a history of drug or alcohol dependence in the past 3 years

          -  Known sensitivity to lidocaine or OP-1

          -  Female with reproductive capability

          -  Has other serious, non-malignant, significant, acute or chronic medical or psychiatric
             illness that, in the judgment of the Investigator, could compromise subject safety,
             limit the subject's ability to complete the study, and/or compromise the objectives of
             the study.

          -  Prior use of a bone morphogenetic protein.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 40 Years old.


Patient description (medical language): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient description (patient's own words): I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Does the patient match the trial criteria? 1