Hydros and Hydros-TA Joint Therapy for Pain Associated with Knee OA; A Multi-center, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Hydros and Hydros-TA Joint Therapies for Management of Pain Associated with Osteoarthritis in the Knee

Completed

Conditions: Joint Degeneration
Osteoarthritis
10023213

Registration Number: NL-OMON40374

Lead Sponsor: Carbylan Therapeutics, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 210

Inclusion Criteria

1. Have radiographic evidence within the prior 6 months, as shown in the radiology reports, of OA grade 2 or 3 in one knee using Kellgren-Lawrence Grading for OA, and verified by the enrolling physician.
a. Grade 2 defined as definite osteophytes with unimpaired joint space.
b. Grade 3 defined as definite osteophytes with moderate joint space narrowing.
2. Subjects are required to be on routine pain medication (at least 5 of the last 7 days) at screening.
3. Treatment knee criteria:
a. WOMAC Pain subscale score of 4-8 points on a NRS 3.1 Index (where 0= no pain and 10= worst pain) for the average of the five pain questions with routine medication for at least 5 of the last 7 days.
b. An increase of 1 point at baseline (after 4 days washout) for Subjects on pain medication at screening (WOMAC Pain subscale score of 5-9 after washout).
4. Non-treatment knee average WOMAC Pain subscale score <=3 points at baseline.
5. Symptoms in the treatment knee for at least 12 months.
6. Fully ambulatory Subject (ability to perform a 15 meters walk test).
7. Male and female Subjects 40 through 85 years of age.
8. Willing to use only acetaminophen (paracetamol) (up to 3 grams/day) for pain relief during the duration of the study.
9. Written consent to participate in the clinical study following Subject*s review of the COR1.1 Study Subject Information and Consent Form.
10. Able to understand the requirements of the study and willing to comply with all treatment and study evaluations for the duration of the trial.
11. If female, must use a medically acceptable form of contraception for at least 1 month prior to Screening and continue use for the duration of the study . Otherwise, females must be surgically sterile, or postmenopausal (as documented in medical history) for at least 1 year.
12. Have completed the pain and OA medication washout period.
13. Willing to abstain from any pain medications for 24 hours prior to all study visits.

Exclusion Criteria

1. Non-treatment knee joint pain >3 points average WOMAC Pain subscale scores.
2. Any Subject with an increase in WOMAC A pain subscale score of <1point after 4 day wash-out period.
3. Secondary OA (acute knee injury, rheumatoid arthritis, history of joint infection, chondrocalcinosis, osteonecrosis, chronic fibromyalgia) or other chronic autoimmune disease.
4. Generalized symptomatic OA in joints other than the knees, inflammatory joint disease, bursitis, OA in the hips, or other condition that may interfere with study assessments. Diagnosis is from medical history or prior x-rays. Upper extremity OA is NOT excluded.
5. Significant valgus/varus deformities, ligamentous laxity, or meniscal instability as assessed by the Investigator.
6. Active infection in either knee joint or adjacent tissues or positive synovial fluid culture of any joint.
7. Any contraindications for IA injection or aspiration.
8. Knee surgery or trauma within 3 months prior to enrollment or planned joint surgery for the period of study duration.
9. IA steroid injection in the knee and/or use of systemic (oral) corticosteroids within 3 months prior to enrollment. Inhaled steroids are NOT excluded.
10. IA hyaluronan injection in the treatment knee within 6 months prior to enrollment.
11. BMI >40.
12. Known hypersensitivity/allergic/anaphylactic reactions to local anesthetics.
13. Known sensitivity to corticosteroids, or hyaluronan-based products.
14. Arthroscopy of either knee or in any other joint within 3 months prior to enrollment.
15. Uncontrolled diabetes, uncontrolled hypertension or active infection end-state hepatic or renal disease; or Subjects on immunosuppressive therapy.
16. Current use of IA injections.
17. Current use of any systemic steroid therapies (oral, IV or IM), inhaled steroids
are permitted.
18. Initiated a physical therapy or exercise regime within 3 months prior to enrollment.
19. Use of braces within 3 months prior to enrollment or planned use of braces for the period of study duration.
20. Clinically significant conditions that would interfere with accuracy of study evaluations including but not limited to:
a. Fibromyalgia
b. Chronic Fatigue Syndrome
c. Gout
d. Malignant neoplastic disease
e. IA tumor
f. Peripheral neuropathy
g. Vascular insufficiency
h. Hemiparesis
i. Baker's cyst
20. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder, including but not limited to:
a. Bipolar disorders
b. Psychotic disorders
c. Depression with hospital admission within last 5 years
d. Suicide attempt within last 5 years
e. Active alcohol/drug abuse within last 2 years
f. Any other factors that the investigator feels would interfere with study evaluations and study participation
21. Subjects on anti-depressive medications for significant depression or anxiety.
22. Participation in another clinical trial and/or treatment received with any investigational agent within 30 days before enrollment.
23. Active asthma that may require periodic treatment with systemic steroid during the study period.
24. Ongoing litigation for workers compensation for musculoskeletal injuries or disorders.
25. Planned/anticipated surgery of the treatment knee during the study period.
26. Female Subjects who are pregnant and/or nursing or planning a pregnancy during the course of

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study is to evaluate Hydros-TA treated Subjects<br /><br>for the reduction of OA symptoms, compared to Hydros at 2 weeks and Hydros-TA<br /><br>compared to TA 10 mg at 26 weeks, as assessed by the WOMAC OA Index. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives will include a strict OMERACT-OARSI responder rate, time<br /><br>of onset of pain relief, time to treatment failure, change from baseline in<br /><br>WOMAC A (Pain), B (Stiffness) and C (Function), change from baseline in<br /><br>physician and subject global assessment scores at each follow-up visit, and a<br /><br>rescue medication use.<br /><br><br /><br>The safety of Hydros-TA will be evaluated by the assessment of all adverse<br /><br>events and through physical examinations.</p><br>