Cingal Study for Knee Osteoarthritis

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

The purpose of this study is to see if a single injection of Cingal into the knee provides safe relief of pain caused by osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Device: Saline; Device: Hyaluronic Acid and TH (Cingal®); Device: Hyaluronic Acid (Monovisc®)

Detailed Description

This study compared three groups of subjects. Group One received a single injection of Cingal (Hyaluronic Acid plus Triamcinolone Hexacetonide). Group Two received a single injection of Monovisc (Hyaluronic Acid). Group Three received a single injection of saline as a placebo.

• Study Type: Interventional
• Enrollment (Actual): 368
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Orthopaedics Clinic Multiprofile Hospital for Active Treatment "Sveti Georgi"
  • Sofia, Bulgaria
    • Clinic of Orthopaedics and Traumatology, University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna"
  • Sofia, Bulgaria
    • Consultative Outpatients' Medical Office for Rheumatologic Diseases
  • Sofia, Bulgaria
    • Department of Orthopaedics and Traumatology Multiprofile Hospital for Active Treatment Lyulin Hospital
  • Sofia, Bulgaria
    • Department of Orthopaedics Traumatology - Tokuda Hospital Sofia
• Canada
  • Halifax, Canada
    • QEII Health Sciences
  • Alberta
    • Red Deer, Alberta, Canada
      • Red Deer Regional Hospital Center
  • Ontario
    • Oakville, Ontario, Canada, L6K 3T7
      • Deakon Medicine Professional Corporation
    • Toronto, Ontario, Canada
      • Sports Medicine Specialists
• Czechia
  • Brno, Czechia
    • Revmacentrum MUDr. Moster, s.r.o.
  • Plzen, Czechia
    • Faculty Hospital Plzen
  • Prague, Czechia
    • Institute of Rheumatology
  • Prague, Czechia
    • Thomayer Hospital Rheumatology Department
  • Uherske Hradiste, Czechia
    • MEDICAL Plus s.r.o.
• Hungary
  • Budapest, Hungary
    • Uzsoki Hospital, Department of Traumatology
  • Budapest, Hungary
    • Health Center of Downtown-Lipotvaros, Orthopedic Outpatient Clinic
  • Budapest, Hungary
    • Semmelweis Egyetem Orthopaedic Clinic
  • Gyor, Hungary
    • Petz Aladar County Teachin Hospital, Traumatology, Orthopaedics and Hand Surgery Centre
  • Kecskemet, Hungary
    • Jutrix Medical Llc
  • Kiskunfelegyhaza, Hungary
    • Medidea Bt.
  • Mako, Hungary
    • G&V Pharma-Med Bt.
• Poland
  • Bialystok, Poland
    • Osteo-Medic s.c.
  • Gliwice, Poland
    • NZOZ Medi SPATX
  • Kielce, Poland
    • ARTIMED Niepubliczny Zakład Opieki Zdrowotnej
  • Krakow, Poland
    • CenterMed Krakow Sp. x. o.o.
  • Lodz, Poland
    • Radlinski Regional Centre of Orthopeadics and Rehabilitation of Locomotor Organs
  • Sopot, Poland
    • Wojewódzki Zespół Reumatologiczny im. Dr Jadwigi Titz-Kosko

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject is 40 - 75 years old with a Body Mass Index (BMI)≤ 40 kg/m2
• 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.

Exclusion Criteria:

• Subject received an intra-articular (IA) injection of Hyaluronic Acid (HA) and/or steroid in either knee within 6 months of signing the informed consent form (ICF).
• Subject had an arthroscopy of either knee within 3 months of signing the informed consent form (ICF).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; Single injection of 0.9% saline supplied as a 4 milliliter (mL) unit dose in a 5mL glass syringe	Device: Saline; Saline placebo packaged to look identical to comparator syringes. Injection into knee.
Experimental: Hyaluronic Acid and TH (Cingal®); Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe	Device: Hyaluronic Acid and TH (Cingal®); Injection into knee; Other Names: Cingal®
Active Comparator: Hyaluronic Acid (Monovisc®); Single injection of sodium hyaluronate supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe	Device: Hyaluronic Acid (Monovisc®); Injection into knee; Other Names: Monovisc®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT)	The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (ITT population). 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 difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	12 Weeks
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (PP)	The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (PP population). 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 difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)	The change in knee pain from baseline to 1 week post treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (ITT population). 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 difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	1 Week
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)	The change in knee pain from baseline to 3 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (ITT population). 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.	3 Weeks
Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT)	The change from baseline to 12 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 mm = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	12 Weeks
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT)	The change from baseline to 1 week in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	1 Week
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT)	Mean change from baseline to 3 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	3 Weeks
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT)	Mean change in knee pain from baseline to 26 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group. The WOMAC Pain Score is a validated 100mm visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	26 Weeks
Evaluator Global Assessment Comparing Cingal® to Saline (ITT)	Mean change from baseline to 12 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	12 Weeks
Evaluator Global Assessment Comparing Cingal® to Monovisc® (ITT)	Mean change from baseline to 1 week in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	1 Week
Evaluator Global Assessment Comparing Cingal® to Monovisc® (ITT)	Mean change from baseline to 3 weeks in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	3 Week
Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT)	Mean change from baseline to 26 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	26 Weeks
Evaluator Global Assessment Comparing Cingal® to Saline (ITT)	Mean change from baseline to 26 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	26 Weeks
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (PP)	Mean change in knee pain from baseline to 1 week as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (PP population). 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 difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	1 Week
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (PP)	Mean change in knee pain from baseline to 3 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (PP population). 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 difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	3 Weeks
Patient Global Assessment (PGA) Comparing Cingal® to Saline (PP)	Mean change from baseline to 12 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (PP population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	12 Weeks
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (PP)	The post treatment Responder Rate comparing Cingal® and Monovisc® at 1 week is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index (PP population). The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. A higher percentage of subjects responding indicates a better outcome.	1 Week
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (PP)	Mean change from baseline to 3 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (PP population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	3 Weeks
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline. (PP)	Mean change in knee pain from baseline to 26 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (PP population). The WOMAC Pain Score is a validated 100mm visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.	26 Weeks
Evaluator Global Assessment Comparing Cingal® to Saline (PP)	Mean change from baseline to 12 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	12 Weeks
Evaluator Global Assessment Comparing Cingal® and Monovisc® (PP).	Mean change from baseline to 1 week in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	1 Week
Evaluator Global Assessment Comparing Cingal® to Monovisc® (PP)	Mean change from baseline to 3 weeks in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	3 Week
Patient Global Assessment (PGA) Comparing Cingal® to Saline (PP)	Mean change from baseline to 26 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (PP population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.	26 Weeks
Evaluator Global Assessment Comparing Cingal® to Saline (PP)	Mean change from baseline to 26 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.	26 Weeks
OMERACT-OARSI Responder Index Comparing Cingal® to Saline (ITT)	The post treatment Responder Rate at 12 weeks is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index. The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. The criteria for response are (1) improvement in pain or physical function ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment. A higher percentage of subjects responding indicates a better outcome.	12 Weeks
OMERACT-OARSI Responder Index Comparing Cingal® to Saline (PP)	The post treatment Responder Rate comparing Cingal® and Saline at 12 weeks is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index (PP population). The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. The criteria for response are (1) improvement in pain or physical function ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment. A higher percentage of subjects responding indicates a better outcome.	12 Weeks

Collaborators and Investigators

• Sponsor: Anika Therapeutics, Inc.
• Investigators: Principal Investigator: Laszlo Hangody, MD, Uzsoki Hospital

Publications and helpful links

General Publications

• Hangody L, Szody R, Lukasik P, Zgadzaj W, Lenart E, Dokoupilova E, Bichovsk D, Berta A, Vasarhelyi G, Ficzere A, Hangody G, Stevens G, Szendroi M. Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial. Cartilage. 2018 Jul;9(3):276-283. doi: 10.1177/1947603517703732. Epub 2017 May 23.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: June 28, 2013
• First Posted (Estimated): July 3, 2013

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Knee osteoarthritis; Hyaluronic acid; Steroid Injection; HA Injection; Knee injection
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: Cingal 13-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO