Randomized, Double-Blind, Active Comparator 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
- Knee Osteoarthritis
- Sponsor
- Anika Therapeutics, Inc.
- Enrollment
- 576
- Locations
- 19
- Primary Endpoint
- Change From Baseline in WOMAC Pain Score at 26 Weeks (ITT Population)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a multi-center, randomized, double-blind, parallel group, active comparator controlled trial to evaluate the efficacy and safety of a single injection of Cingal for the relief of joint pain in subjects with OA of the knee.
Detailed Description
Cingal 16-02 is a multi-center, randomized, double-blind, active comparator controlled study designed to evaluate the relative contributions of the individual constituents (Hyaluronic Acid and Triamcinolone Hexacetonide) in the Cingal combination product to pain relief as measured by the change in WOMAC Pain from baseline through 26 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Screening Inclusion Criteria
- •Subject is 40-75 years old, with a Body Mass Index (BMI) ≤ 40 kg/m
- •Subject has Kellgren-Lawrence (K-L) severity grade I, 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 NSAIDs, except acetaminophen/paracetamol, at least seven days before the treatment injection and through the completion of the study.
- •Subject is willing to use only acetaminophen/paracetamol (up to a maximum of 4.0 grams per day per the package insert) 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/paracetamol.
- •Subject is willing to maintain a stable dose of oral glucosamine and/or chondroitin sulfate products throughout the study, if taken prior to signing the informed consent form (ICF).
Exclusion Criteria
- •Subject received an IA injection of Hyaluronic Acid (HA) and/or steroid in either knee within 6 months of signing the informed consent form (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 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 10 degrees in either knee.
- •Subject has a clinically apparent tense effusion of the index knee.
Arms & Interventions
Cingal
Cingal is a combination product consisting of 88 milligrams of cross-linked HA (hyaluronic acid) with 18 milligrams of TH (triamcinolone hexacetonide) in a 4 milliliter (mL) intra-articular injection.
Intervention: Cingal
Monovisc
Monovisc is a device that consists of 88 milligrams of cross-linked HA (hyaluronic acid) in a 4 milliliter (mL) intra-articular injection.
Intervention: Monovisc
Triamcinolone Hexacetonide (TH)
Triamcinolone hexacetonide (TH) is a corticosteroid supplied in a 20 milligram per 1 milliliter (20 mg/mL) intra-articular injection.
Intervention: Triamcinolone Hexacetonide
Outcomes
Primary Outcomes
Change From Baseline in WOMAC Pain Score at 26 Weeks (ITT Population)
Time Frame: 26 weeks
The change from baseline in knee pain as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal group to the TH group. The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the change from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.
Secondary Outcomes
- Change From Baseline in WOMAC Stiffness Score at 26 Weeks (ITT Population)(26 weeks)
- Change From Baseline in WOMAC Pain Score at 3 Weeks (ITT Population)(3 weeks)
- OMERACT-OARSI Responder Index at 26 Weeks Post Treatment Comparing the Cingal Group to the TH Group (ITT Population)(26 weeks)
- Change From Baseline in WOMAC Physical Function Score at 26 Weeks (ITT Population)(26 weeks)
- Change From Baseline in Total WOMAC Score at 26 Weeks (ITT Population)(26 weeks)
- Change From Baseline in Patient Global Assessment at 26 Weeks (ITT Population)(26 weeks)
- Change From Baseline in the Evaluator Global Assessment at 26 Weeks (ITT Population)(26 weeks)
- Change From Baseline in WOMAC Pain Score at 1 Week (ITT Population)(1 week)
- The Usage of Rescue Medication (Acetaminophen) Through 26 Weeks (ITT Population)(26 weeks)