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CompletedNCT03390036Cingal17-02Updated May 31, 2023Results posted

Study of Cingal for the Relief of Knee Osteoarthritis Compared to Triamcinolone Hexacetonide at 39 Weeks Follow up

A Phase 3 interventional study of Cingal and Monovisc in Knee Osteoarthritis, sponsored by Anika Therapeutics, Inc.. Completed at 17 sites in 2 countries. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-05-31.

Sponsored by Anika Therapeutics, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
526
Allocation
Randomized
Ages
40 Years to 75 Years
Sex
All
01

Study summary

Extension study to Cingal 16-02 to obtain 39-week safety and efficacy follow-up data

Read the detailed description

Extension Study to Cingal 16-02: Trial Extension to 39 Week Follow Up in the 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

02

Conditions studied

  • Knee Osteoarthritis

Keywords

  • Osteoarthritis
  • Intra-articular Injection
  • Hyaluronic Acid
  • Triamcinolone Hexacetonide
03

Who can participate

Ages eligible
40 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Only subjects that were enrolled and met the inclusion criteria for the Cingal 16-02 trial and signed the informed consent are eligible for Cingal 17-02 trial.
  2. Subject is able to understand and comply with the requirements of Cingal 17-02 and voluntarily provides consent.

Exclusion criteria

Exclusion Criteria:

Patients will not be rescreened at enrollment to Cingal 17-02 as these patients met the inclusion / exclusion criteria for the Cingal 16-02 clinical trial.

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
526 participants (actual)

Study arms

  • Experimental
    Cingal

    Cingal is a combination product consisting of 88 milligrams of crosslinked HA (hyaluronic acid) with 18 milligrams of TH (triamcinolone hexacetonide) in a 4 milliliter (mL) intra-articular injection.

    Combination Product: Cingal

  • Active comparator
    Monovisc

    Monovisc is a device that consists of 88 milligrams of cross-linked HA (hyaluronic acid) in a 4 milliliter (mL) intra-articular injection.

    Device: Monovisc

  • Active comparator
    Triamcinolone Hexacetonide (TH)

    Triamcinolone hexacetonide (TH) is a corticosteroid supplied in a 20 milligram per 1 milliliter (20 mg/mL) intra-articular injection.

    Drug: Triamcinolone Hexacetonide

Interventions

  • Combination productCingal

    Hyaluronic Acid with Triamcinolone Hexacetonide

    Also known as: HA + TH

  • DeviceMonovisc

    Hyaluronic Acid

    Also known as: HA

  • DrugTriamcinolone Hexacetonide

    Triamcinolone Hexacetonide

    Also known as: TH

05

What researchers measure

Primary outcomes

  1. OMERACT-OARSI Responder Rate at 39 Weeks

    The post treatment Responder Rate at 39 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.

    Time frame: 39 weeks

Secondary outcomes

  1. Change From Baseline in WOMAC Pain Score at 39 Weeks

    The change from baseline in knee pain as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score at 39 weeks post treatment comparing the Cingal group to the Triamcinolone Hexacetonide group. The WOMAC Pain Score is a validated visual analog scale from 0 to 100 mm, where a higher score is equal to a higher pain level. A negative number for the difference from baseline indicates improvement in pain. A greater negative difference from baseline indicates a better outcome.

    Time frame: 39 Weeks

  2. Change From Baseline in WOMAC Physical Function Score at 39 Weeks

    This endpoint compares the change of the WOMAC Physical Function Score from baseline to Week 39 between the Cingal and Triamcinolone Hexacetonide arms. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Score is a validated visual analog scale from 0 to 100 mm, where a higher score is equal to a higher degree of functional limitation. A negative number for the change from baseline indicates improvement in physical function.

    Time frame: 39 Weeks

  3. Change From Baseline in WOMAC Stiffness Score at 39 Weeks

    The change from baseline in knee stiffness as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score at 39 weeks post treatment comparing the Cingal group to the Triamcinolone Hexacetonide group. The WOMAC Stiffness Score is a validated visual analog scale from 0 to 100 mm, where a higher score is equal to a higher degree of stiffness. A negative number for the change from baseline indicates improvement in knee stiffness.

    Time frame: 39 Weeks

  4. Change From Baseline in Total WOMAC Score at 39 Weeks

    The change from baseline as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 39 weeks post treatment comparing the Cingal group to the Triamcinolone Hexacetonide group. The Total WOMAC Score is determined from the SUM of the scores from the WOMAC Pain Score, the WOMAC Stiffness Score, and the WOMAC Physical Function Score, resulting in a final range for Total Score from 0 mm to 240 mm. A higher Total WOMAC Score indicates a higher overall degree of pain, stiffness and functional limitations. A negative number for the change from baseline indicates improvement in the Total WOMAC Score.

    Time frame: 39 Weeks

  5. Change From Baseline in Patient Global Assessment at 39 Weeks

    Comparison of the change of the Patient Global Assessment from baseline to 39 weeks between the Cingal and Triamcinolone Hexacetonide arms (ITT population). The Patient Global Assessment is done by the subject, and answers the question "Considering all the ways the osteoarthritis in your index knee bothers you, what is your assessment of how much your knee is bothering you today?" The Patient Global Assessment is scored on a 0 to 100 mm visual analog scale, where a higher number means the patient is bothered to a higher degree. A negative number for the change from baseline indicates a reduction (improvement) in the assessment.

    Time frame: 39 Weeks

  6. Change From Baseline in Evaluator Global Assessment at 39 Weeks

    Comparison of the change of the Evaluator Global Assessment from baseline to 39 weeks between the Cingal and Triamcinolone Hexacetonide arms (ITT population). The Evaluator Global Assessment is done by the Blinded 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 0 to 100 mm visual analog scale, where a higher number means the Evaluator assesses that the patient is bothered to a higher degree. A negative number for the change from baseline indicates a reduction (improvement) in the assessment.

    Time frame: 39 Weeks

  7. The Usage of Rescue Medication (Acetaminophen) at Week 39

    The usage of rescue medication (number of pills of acetominophen) at Week 39 weeks post treatment in the Cingal group compared to the Triamcinolone Hexacetonide group.

    Time frame: 39 Weeks

06

Results

Posted May 31, 2023
Limitations and caveats
Cingal 17-02, an extension study of Cingal 16-02, did not include a placebo arm, and was an all-active trial.

Participant flow

Subjects enrolled in Cingal 16-02 were given the option to enroll in Cingal 17-02 for a 39-week follow-up. 233 subjects in the Cingal arm (95%), 230 subjects in the Monovisc arm (93%), and 63 subjects in the Triamcinolone Hexacetonide arm (90%) elected to enroll in the extension study.

Participant flow — Overall Study
MilestoneCingalMonoviscTriamcinolone Hexacetonide (TH)
Started23323063
Completed23123063
Not completed200
Withdrew: Lost to follow-up100
Withdrew: Lack of efficacy100

Outcome measures

PrimaryOMERACT-OARSI Responder Rate at 39 Weeks

The post treatment Responder Rate at 39 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.

Time frame:
39 weeks
Reported as:
Number · Percentage of subjects
OMERACT-OARSI Responder Rate at 39 Weeks
Percentage of subjectsCingalMonoviscTriamcinolone Hexacetonide (TH)
OMERACT-OARSI Responder Rate at 39 Weeks91.292.493.2
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.8106
SecondaryChange From Baseline in WOMAC Pain Score at 39 Weeks

The change from baseline in knee pain as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score at 39 weeks post treatment comparing the Cingal group to the Triamcinolone Hexacetonide group. The WOMAC Pain Score is a validated visual analog scale from 0 to 100 mm, where a higher score is equal to a higher pain level. A negative number for the difference from baseline indicates improvement in pain. A greater negative difference from baseline indicates a better outcome.

Time frame:
39 Weeks
Reported as:
Mean · Millimeters (mm)
Change From Baseline in WOMAC Pain Score at 39 Weeks
Millimeters (mm)CingalMonoviscTriamcinolone Hexacetonide (TH)
Change from Baseline in WOMAC Pain 39 Weeks-46.3 ± 20.2-47.2 ± 18.6-43.6 ± 21.4
Baseline WOMAC Pain in mm63.3 ± 11.063.3 ± 11.363.8 ± 11.3
39 Week WOMAC Pain in mm17.0 ± 19.316.0 ± 18.620.1 ± 21.1
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.3007
SecondaryChange From Baseline in WOMAC Physical Function Score at 39 Weeks

This endpoint compares the change of the WOMAC Physical Function Score from baseline to Week 39 between the Cingal and Triamcinolone Hexacetonide arms. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Score is a validated visual analog scale from 0 to 100 mm, where a higher score is equal to a higher degree of functional limitation. A negative number for the change from baseline indicates improvement in physical function.

Time frame:
39 Weeks
Reported as:
Mean · Millimeters (mm)
Change From Baseline in WOMAC Physical Function Score at 39 Weeks
Millimeters (mm)CingalMonoviscTriamcinolone Hexacetonide (TH)
Change from Baseline WOMAC Function 39 Weeks-42.5 ± 22.4-43.5 ± 20.7-41.1 ± 22.5
Baseline WOMAC Function60.8 ± 15.260.8 ± 15.861.8 ± 15.7
39 Week WOMAC Function18.4 ± 19.817.3 ± 18.620.7 ± 21.3
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.6354
SecondaryChange From Baseline in WOMAC Stiffness Score at 39 Weeks

The change from baseline in knee stiffness as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score at 39 weeks post treatment comparing the Cingal group to the Triamcinolone Hexacetonide group. The WOMAC Stiffness Score is a validated visual analog scale from 0 to 100 mm, where a higher score is equal to a higher degree of stiffness. A negative number for the change from baseline indicates improvement in knee stiffness.

Time frame:
39 Weeks
Reported as:
Mean · Millimeters (mm)
Change From Baseline in WOMAC Stiffness Score at 39 Weeks
Millimeters (mm)CingalMonoviscTriamcinolone Hexacetonide (TH)
Change from Baseline in WOMAC Stiffness 39 Weeks-39.8 ± 24.4-42.0 ± 22.4-38.0 ± 24.9
Baseline WOMAC Stiffness in mm57.7 ± 19.359.2 ± 18.157.9 ± 17.6
39 Week WOMAC Stiffness in mm17.9 ± 20.017.2 ± 18.619.9 ± 21.9
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.5754
SecondaryChange From Baseline in Total WOMAC Score at 39 Weeks

The change from baseline as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 39 weeks post treatment comparing the Cingal group to the Triamcinolone Hexacetonide group. The Total WOMAC Score is determined from the SUM of the scores from the WOMAC Pain Score, the WOMAC Stiffness Score, and the WOMAC Physical Function Score, resulting in a final range for Total Score from 0 mm to 240 mm. A higher Total WOMAC Score indicates a higher overall degree of pain, stiffness and functional limitations. A negative number for the change from baseline indicates improvement in the Total WOMAC Score.

Time frame:
39 Weeks
Reported as:
Mean · Millimeters (mm)
Change From Baseline in Total WOMAC Score at 39 Weeks
Millimeters (mm)CingalMonoviscTriamcinolone Hexacetonide (TH)
Change from Baseline in Total WOMAC 39 Weeks-128.4 ± 63.1-132.6 ± 56.6-122.7 ± 62.2
Baseline Total WOMAC in mm181.8 ± 40.6183.4 ± 39.4183.5 ± 38.4
39 Week Total WOMAC in mm53.4 ± 58.150.8 ± 54.660.8 ± 62.5
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.4759
SecondaryChange From Baseline in Patient Global Assessment at 39 Weeks

Comparison of the change of the Patient Global Assessment from baseline to 39 weeks between the Cingal and Triamcinolone Hexacetonide arms (ITT population). The Patient Global Assessment is done by the subject, and answers the question "Considering all the ways the osteoarthritis in your index knee bothers you, what is your assessment of how much your knee is bothering you today?" The Patient Global Assessment is scored on a 0 to 100 mm visual analog scale, where a higher number means the patient is bothered to a higher degree. A negative number for the change from baseline indicates a reduction (improvement) in the assessment.

Time frame:
39 Weeks
Reported as:
Mean · Millimeters (mm)
Change From Baseline in Patient Global Assessment at 39 Weeks
Millimeters (mm)CingalMonoviscTriamcinolone Hexacetonide (TH)
Change from Baseline in Patient Global 39 weeks-38.6 ± 25.4-38.2 ± 22.8-36.7 ± 28.0
Baseline Patient Global in mm57.0 ± 18.956.0 ± 18.658.2 ± 20.3
39 Week Patient Global in mm18.4 ± 19.817.8 ± 19.421.5 ± 22.1
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.5596
SecondaryChange From Baseline in Evaluator Global Assessment at 39 Weeks

Comparison of the change of the Evaluator Global Assessment from baseline to 39 weeks between the Cingal and Triamcinolone Hexacetonide arms (ITT population). The Evaluator Global Assessment is done by the Blinded 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 0 to 100 mm visual analog scale, where a higher number means the Evaluator assesses that the patient is bothered to a higher degree. A negative number for the change from baseline indicates a reduction (improvement) in the assessment.

Time frame:
39 Weeks
Reported as:
Mean · Millimeters (mm)
Change From Baseline in Evaluator Global Assessment at 39 Weeks
Millimeters (mm)CingalMonoviscTriamcinolone Hexacetonide (TH)
Change from Baseline in Evaluator Global 39 eeks-37.1 ± 21.3-37.7 ± 19.9-39.1 ± 22.1
Baseline Evaluator Global in mm52.9 ± 17.252.3 ± 17.756.6 ± 18.1
39 Week Evaluator Global in mm15.8 ± 16.514.6 ± 16.517.4 ± 15.6
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.4551
SecondaryThe Usage of Rescue Medication (Acetaminophen) at Week 39

The usage of rescue medication (number of pills of acetominophen) at Week 39 weeks post treatment in the Cingal group compared to the Triamcinolone Hexacetonide group.

Time frame:
39 Weeks
Reported as:
Mean · Number of pills
The Usage of Rescue Medication (Acetaminophen) at Week 39
Number of pillsCingalMonoviscTriamcinolone Hexacetonide (TH)
The Usage of Rescue Medication (Acetaminophen) at Week 397.9 ± 39.56.0 ± 18.76.9 ± 22.8
Statistical analysis
  • Cingal vs Triamcinolone Hexacetonide (TH) · ANOVA · p = 0.7931

Adverse events

Collected over Adverse events were collected from the 26 Week visit (the last one in the Cingal 16-02 study) through the 39 Week visit in the Cingal 17-02 extension study.. Non-serious events are listed at a 1.0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cingal0/233 (0%)0/233 (0%)20/233 (8.6%)
Monovisc0/230 (0%)0/230 (0%)19/230 (8.3%)
Triamcinolone Hexacetonide (TH)0/63 (0%)0/63 (0%)6/63 (9.5%)
Most frequent other events
Most frequent other events
EventCingalMonoviscTriamcinolone Hexacetonide (TH)
ArthralgiaMusculoskeletal and connective tissue disorders8/2334/2300/63
Viral upper respiratory tract infectionInfections and infestations2/2332/2302/63
Abdominal painGastrointestinal disorders0/2330/2302/63
HeadacheNervous system disorders7/2336/2300/63
Musculoskeletal painMusculoskeletal and connective tissue disorders1/2334/2300/63
Spinal painMusculoskeletal and connective tissue disorders1/2333/2301/63
ArrythmiaCardiac disorders1/2330/2301/63

Baseline characteristics

ITT Population

Age, Continuous
Age, Continuous(years)CingalMonoviscTriamcinolone Hexacetonide (TH)Total
Mean57.8 ± 8.857.7 ± 8.959.2 ± 8.457.9 ± 8.8
Sex: Female, Male
Sex: Female, Male(Participants)CingalMonoviscTriamcinolone Hexacetonide (TH)Total
Female16515244361
Male687819165
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CingalMonoviscTriamcinolone Hexacetonide (TH)Total
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White23323063526
More than one race0000
Unknown or Not Reported0000
Baseline WOMAC Pain in Index Knee
Baseline WOMAC Pain in Index Knee(millimeters (mm))CingalMonoviscTriamcinolone Hexacetonide (TH)Total
Mean63.5 ± 11.163.7 ± 11.464.6 ± 10.963.7 ± 11.2
07

Study locations

17 sites
  • Health Center of Downtown-Lipotvaros, Orthopedic Outpatient Clinic (Belvárosi-Lipótvárosi Egészségügyi Szolgálat Ortopeadia)
    Budapest, 1051, Hungary
  • Uzsoki Hospital, Department of Traumatology
    Budapest, 1145, Hungary
  • Jutrix Medical Llc
    Budapest, 6000, Hungary
  • Magyar Honvedseg, Egeszseugyi Kozpont, Balesteti Sebeszeti Osztaly
    Budapest, Hungary
  • DE KK Ortopediai Klinika
    Debrecen, Hungary
  • Medidea Bt.
    Kiskunfelegyhaza, Hungary
  • Kastelypark Klinka
    Tata, Hungary
  • Zdrowie Osteo-Medic
    Białystok, Poland
  • Szpital Świętego Łukasza S.A.
    Bielsko-Biała, Poland
  • NZOZ Medi SPATX
    GLIwice, Poland
  • Centrum Medyczne 4M Plus
    Kraków, Poland
  • NOVAMED Jackowiak Krajewski Spółka Jawna
    Toruń, Poland
  • Centrum Medyczne Amed Warszawa Targówek
    Warsaw, Poland
  • ETG Network, Warsaw
    Warsaw, Poland
  • ETG Network
    Warsaw, Poland
  • Medical University of Lodz
    Łódź, Poland
  • Lubelskie Centrum Diagnostyczne
    Świdnik,, Poland
08

References and documents

Study documents

  • Study protocol · Jan 3, 2018
  • Statistical analysis plan · May 25, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — There is no plan to make individual participant data available to other researchers

09

Registry details

Key details

Study ID
NCT03390036
Lead sponsor
Anika Therapeutics, Inc.
Responsible party
Sponsor
First posted
Jan 4, 2018
Start date
Dec 7, 2017
Primary completion
Jul 30, 2018
Completion
Jul 30, 2018
Results posted
May 31, 2023
Last update
May 31, 2023

Study contacts

Laszlo Hangody, MD
principal investigator · Uzsoki Hospital, Department of Traumatology

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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