A Randomized, Double-Blind, Placebo Controlled, Multi-Center Study of a Single Injection Cross-Linked Sodium Hyaluronate Combined With Triamcinolone Hexacetonide (Cingal®) to Provide Symptomatic Relief of Osteoarthritis of the Knee
Overview
- Phase
- Phase 3
- Intervention
- Cingal
- Conditions
- Osteoarthritis, Knee
- Sponsor
- Anika Therapeutics, Inc.
- Enrollment
- 231
- Locations
- 24
- Primary Endpoint
- Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multi-center, randomized, double-blind, parallel group, placebo controlled trial to compare the safety and effectiveness of a single injection of Cingal® to a single injection of Triamcinolone Hexacetonide (TH) to achieve pain relief and other symptoms of osteoarthritis of the knee.
Detailed Description
To determine the contribution of Triamcinolone Hexacetonide (TH) when combined with sodium hyaluronate for pain relief, both in terms of magnitude and duration, when used as single injection, as compared to a single injection of TH alone in subjects diagnosed with osteoarthritis of the knee. A saline placebo is included within the trial to set the expectation of a return to Baseline pain for the subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is 40-75 years old.
- •Body Mass Index (BMI) ≤ 40 kg/m
- •Subject has Kellgren-Lawrence (K-L) severity grade II or III in the Index knee as determined by X-Ray. Contralateral knee: K-L severity grade 0, I or II.
- •Subject has had at least two signs and at least two symptoms of OA disease (based on the European League Against Rheumatism (EULAR) recommendations for diagnosing knee OA) in the Index knee for at least 6 months despite conservative treatment (weight reduction, physical therapy, pain medications, etc.). The EULAR signs and symptoms are as follows:
- •Signs: crepitus, restricted movement and bony enlargement
- •Symptoms: persistent knee pain, limited morning stiffness and reduced function
- •Subject must be willing to abstain from other IA treatments of the knee for the duration of the study.
- •Subject is willing to discontinue all analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs), except acetaminophen before the treatment injection and through the completion of the study. NSAIDs should be discontinued through the Screening period.
- •Subject is willing to use only acetaminophen (up to a maximum of 3.0 grams per day) for the treatment of joint pain for the duration of the study. At least forty-eight hours prior to the Baseline Visit and each follow-up visit, the Subject is willing to discontinue use of acetaminophen
- •Subject is willing to maintain a stable dose of oral glucosamine and/or chondroitin sulfate products throughout the study, if taken prior to signing ICF.
Exclusion Criteria
- •Subject received an IA injection of Hyaluronic Acid (HA) and/or steroid in either knee within 6 months of signing the ICF. A Subject will be excluded if they are planning to receive an HA or steroid injection (other than the study injection) in either knee during the course of this study.
- •Subject had an arthroscopy of either knee within 3 months of signing the ICF.
- •Subject had an open surgical procedure of either knee or hip or any surgery of the spine within 12 months of signing ICF. Subject plans to have knee, hip or spine surgery within the study period.
- •Subject has intra-articular trauma to the Index knee. Subject has concurrent multi-system or multi-limb trauma.
- •Subject has evidence or medical history of the following diseases in the Index knee: septic arthritis; inflammatory joint disease; history of Reiter's syndrome; gout; chondrocalcinosis associated with recurrent episodes of acute synovitis of the knee consistent with pseudogout; osteochondritis dissecans, Paget disease of the bone; ochronosis; acromegaly; hemochromatosis; primary osteochondromatosis; known history of Wilson disease; heritable disorders or collagen gene mutations.
- •Subject has a history of cartilage repair surgery in the Index knee within 3 years of signing the ICF.
- •Subject has a history of Anterior cruciate ligament (ACL) repair, reconstruction or injury in the Index knee within 3 years of signing the ICF.
- •Subject has X-Ray findings of acute fractures, severe bone loss, avascular necrosis, severe bone or joint deformity in the Index knee.
- •Subject has significant varus or valgus deformity greater than 8 degrees in either knee.
- •Subject has a clinically apparent tense effusion of the Index knee.
Arms & Interventions
Cingal
Single injection of Cingal: 4 milliliter (mL) dose of 88 mg (22 mg/mL) of cross-linked sodium hyaluronate with 18 mg (4.5 mg/mL) of triamcinolone hexacetonide (TH). Manufactured by Anika Therapeutics.
Intervention: Cingal
Triamcinolone Hexacetonide (TH)
Single injection of Triamcinolone Hexacetonide (TH): 1 milliliter (mL) dose of 20 mg/ml TH. Manufactured by IntraPharm.
Intervention: Triamcinolone Hexacetonide (TH)
Placebo
Single injection of Placebo: 4 milliliter (mL) dose of 0.9% saline. Manufactured by Anika Therapeutics.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
Time Frame: 1 Week
The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative number for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment.
Secondary Outcomes
- The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index(26 Weeks)
- Change From Baseline in Knee Pain as Measured by Visual Analog Scale (VAS) Pain Score(26 Weeks)
- Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Score(26 Weeks)
- Change From Baseline in Knee Pain as Measured by Numerical Rating Scale (NRS) Pain Score(26 Weeks)
- Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Score(26 Weeks)
- Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score(26 Weeks)
- Change From Baseline in the Evaluator Global Assessment (EGA) Score(26 Weeks)
- The Usage of Rescue Medication (Acetaminophen/Paracetamol) at 26 Weeks(26 Weeks)
- Change From Baseline in the Patient Global Assessment (PGA) Score(26 Weeks)