Study of Cingal® and Triamcinolone Hexacetonide for the Relief of Knee Osteoarthritis Pain

NCT04231318 | Completed Phase 3 Results FDA Drug

• 1 other identifier: Cingal 19-01
• Study Type: interventional
• Target: 231
• Locations: 1 country
• Sites: 26

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.

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score

  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 value for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment. A larger negative value indicates lower pain levels and a better outcome.

  26 Weeks

• Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score

  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.

  18 Weeks

• Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score

  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.

  12 Weeks

• Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score

  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.

  6 Weeks

• Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score

  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.

  3 Weeks

• Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score

  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.

  1 Week

Secondary Outcomes (9)

• 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 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) Stiffness Score

  26 Weeks

Study Arms (3)

Cingal

EXPERIMENTAL

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.

Drug: Cingal

Triamcinolone Hexacetonide (TH)

ACTIVE COMPARATOR

Single injection of Triamcinolone Hexacetonide (TH): 1 milliliter (mL) dose of 20 mg/ml TH. Manufactured by IntraPharm.

Drug: Triamcinolone Hexacetonide (TH)

Placebo

PLACEBO COMPARATOR

Single injection of Placebo: 4 milliliter (mL) dose of 0.9% saline. Manufactured by Anika Therapeutics.

Drug: Placebo

Interventions

Cingal DRUG

Single intra-articular injection of Cingal into the knee.

Also known as: HA + TH

Cingal

Triamcinolone Hexacetonide (TH) DRUG

Single intra-articular injection of TH into the knee.

Also known as: TH

Triamcinolone Hexacetonide (TH)

Placebo DRUG

Single intra-articular injection Placebo (0.9% Saline) into the knee.

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is 40-75 years old.
• Body Mass Index (BMI) ≤ 40 kg/m2.
• 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.
• Subject is able to understand and comply with the requirements of the study and voluntarily provides consent.

You may not qualify if:

• 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.
• Subject has knee instability in either knee per the Investigator's assessment.
• Subject requires consistent use of an assistive device (e.g. wheelchair, walker, etc.) Occasional use of a cane is acceptable.
• Subject has medical condition(s) which could affect study assessments or may adversely affect the safety and/or success of the study treatment. This includes but is not limited to the following: a. Peripheral neuropathy severe enough to interfere with evaluation of the subject, b. Vascular insufficiency severe enough to interfere with evaluation of the subject, c. Active fibromyalgia, d. Hemiparesis involving either lower extremity, e. Immunocompromised or immunosuppressive disorder or receiving medications to treat immunosuppressive disorders, f. Systemic bleeding disorder(s), g. Current malignancy or treatment within the last 5 years, except for non-melanoma skin cancer, h. Significant psychiatric disorder, i. Active drug and/or alcohol abuse within the past year, j. Uncontrolled diabetes with a Screening Hemoglobin A1C (HbA1c) of \>7% k. contraindication to Triamcinolone Hexacetonide (TH) including active tuberculosis, herpes simplex keratitis, acute psychoses and systemic mycoses and paracitoses.
• Subject is taking medications at the time the subjects signs the ICF which could interfere with the treatment procedure, healing and/or assessments. This includes but is not limited to oral or injectable anticoagulant treatments, anti-aggregant platelet treatment, chronic opioid analgesics. Low dose aspirin used for cardiovascular protection is allowed if a stable regimen is maintained for the duration of the study.
• Subject is receiving treatment using electromagnetic stimulation and/or low intensity ultrasound in the Index knee at the time of signing the ICF, within 3 months of signing the ICF or plans to receive treatment any time during the study period.

Sponsors & Collaborators

• Anika Therapeutics, Inc.: lead

Study Sites (26)

Orthopaedic Specialist of North America, PLLC DBA OrthoArizona

Chandler, Arizona, 85224, United States

Location

Valley Bone and Joint Specialists

Chandler, Arizona, 85224, United States

Location

Tucson Orthopaedic Institute

Tucson, Arizona, 85712, United States

Location

Advanced Research Center, Inc.

Anaheim, California, 92805, United States

Location

Medvin Clinical Research

Covina, California, 91722, United States

Location

Core Orthopaedic Medical Center (San Dieguito Orthopedic Medical Center)

Encinitas, California, 92024, United States

Location

Infinity Clinical Research

Norco, California, 92860, United States

Location

Dream Team Clinical Research

Pomona, California, 91767, United States

Location

Probe Clinical Research Corporation

Riverside, California, 92501, United States

Location

Artemis Institute for Clinical Research, Riverside

Riverside, California, 92503, United States

Location

Artemis Institute for Clinical Research, San Marcos

Summerville, California, 29485, United States

Location

Medvin Clinical Research

Tujunga, California, 91042, United States

Location

Medvin Clinical Research

Whittier, California, 90602, United States

Location

Tampa Bay Medical Research Inc

Clearwater, Florida, 33761, United States

Location

Shrock Research

Fort Lauderdale, Florida, 33316, United States

Location

Pines Clinical Research, Inc

Hollywood, Florida, 33024, United States

Location

Ascension Research

Pinellas Park, Florida, 33781, United States

Location

Precision Clinical Research, LLC

Sunrise, Florida, 33351, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Best Clinical Trials, LLC

New Orleans, Louisiana, 70115, United States

Location

Anika Therapeutics

Bedford, Massachusetts, 01730, United States

Location

Upstate Clinical Research Associates, LLC

Williamsville, New York, 14221, United States

Location

PMG Research of Wilmington, LLC

Wilmington, North Carolina, 28403, United States

Location

Coastal Carolina Research Center (CCRC)

Mt. Pleasant, South Carolina, 29464-3803, United States

Location

Palmetto Clinical Research

Summerville, South Carolina, 29485, United States

Location

Spectrum Medical, Inc.

Danville, Virginia, 24541, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo(22,2,2,2(11,14))triaconta-1,11,13,24,27,29-hexaene; triamcinolone hexacetonide; Sodium Chloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

There were no limitations or caveats associated with the conduct of this trial.

Results Point of Contact

• Title: Kara Mezger, Executive Director Clinical Affairs
• Organization: Anika Therapeutics

kmezger@anika.com

781.457.9000

Study Officials

• Joanne MacFie

  Anika Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 18, 2020
• Study Start: September 11, 2020
• Primary Completion: May 16, 2022
• Study Completion: May 16, 2022
• Last Updated: August 9, 2023
• Results First Posted: August 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (26)