Osteoarthritis, KneePhase 3NCT04231318

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

A Phase 3 study testing Cingal and Triamcinolone Hexacetonide (TH) in people with Osteoarthritis, Knee, run by Anika Therapeutics, Inc. at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 40 to 75 years
Conditions the study is for: Osteoarthritis, Knee
What is being tested?: Cingal and Triamcinolone Hexacetonide (TH)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 231 participants
Where: 26 sitesUnited States
Study dates: 11 Sep 2020to 16 May 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 12Show fewer

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.
Baseline Inclusion Criteria 24 Subject has a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain-sub-score ≥ 50 mm and ≤ 90 mm in the affected knee and ≤ 30 mm in the contralateral knee on a 100 mm Visual Analog Scale (VAS) scale.

Who cannot join

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.

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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.
Subjects who had an oral, intramuscular, intravenous, rectal suppository or topical (excluded in Index knee only) corticosteroid within 30 days of signing the ICF are excluded. Topical corticosteroid use at any site other than the Index knee is allowed.
Subject has a pre-treatment contraindication to IA injections or aspiration of the Index knee, including cutaneous infection in the injection site area, active IA infection (as suggested by moderate or marked effusion), knee deformity or condition which, in the opinion of the Investigator could jeopardize the sterility or delivery of the IA injection.
Subjects with a history of hypersensitivity to any of the ingredients in the hyaluronan or previous hypersensitivity to the administration of corticosteroids or an inability to tolerate acetaminophen.
Subject has any contraindication to the receipt of a corticosteroid.
Subject is receiving or in litigation for worker's compensation.
Subject is a woman who is pregnant or breastfeeding at the Screening Visit or a woman of child bearing potential who refuses to use effective contraception during the course of the study.
Subject was involved in any other research study involving an investigational product, or a new application of an approved product, within 60 days of signing the ICF.
Subject previously treated with Cingal for knee osteoarthritis.
Baseline Exclusion Criteria 25. Subject has a decrease of ≥ 20 mm in the WOMAC pain-sub-score (average of 5 pain scales) from Screening to Baseline in the Index knee on a 100 mm Visual Analog Scale (VAS) scale.
26. Subject has a synovial fluid aspirate volume > 10 mL in the Index knee. 27. Subject has a contraindication to continue with the study treatment injection based on the visual appearance of the synovial fluid aspirate unless the fluid is examined microscopically prior to injection with no clinically significant findings (e.g. bacteria, crystals or blood).
28. Subject has range of motion of less than 100° flexion in either knee.

Trial locations and contacts

26 sites in 1 country.

City, postcode or hospital

26 sites in 1 country

United States26 sites

Advanced Research Center, Inc.
Anaheim, California, 92805
Anika Therapeutics
Bedford, Massachusetts, 01730
Orthopaedic Specialist of North America, PLLC DBA OrthoArizona
Chandler, Arizona, 85224
Valley Bone and Joint Specialists
Chandler, Arizona, 85224
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Tampa Bay Medical Research Inc
Clearwater, Florida, 33761
Medvin Clinical Research
Covina, California, 91722
Spectrum Medical, Inc.
Danville, Virginia, 24541
Core Orthopaedic Medical Center (San Dieguito Orthopedic Medical Center)
Encinitas, California, 92024
Shrock Research
Fort Lauderdale, Florida, 33316
Pines Clinical Research, Inc
Hollywood, Florida, 33024
Coastal Carolina Research Center (CCRC)
Mt. Pleasant, South Carolina, 29464-3803
Best Clinical Trials, LLC
New Orleans, Louisiana, 70115
Infinity Clinical Research
Norco, California, 92860
Ascension Research
Pinellas Park, Florida, 33781
Dream Team Clinical Research
Pomona, California, 91767
Probe Clinical Research Corporation
Riverside, California, 92501
Artemis Institute for Clinical Research, Riverside
Riverside, California, 92503
Artemis Institute for Clinical Research, San Marcos
Summerville, California, 29485
Palmetto Clinical Research
Summerville, South Carolina, 29485
Precision Clinical Research, LLC
Sunrise, Florida, 33351
Tucson Orthopaedic Institute
Tucson, Arizona, 85712
Medvin Clinical Research
Tujunga, California, 91042
Medvin Clinical Research
Whittier, California, 90602
Upstate Clinical Research Associates, LLC
Williamsville, New York, 14221
PMG Research of Wilmington, LLC
Wilmington, North Carolina, 28403

Other trials in United States

About this study

Official title: 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

Read the 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.

Conditions: Osteoarthritis, Knee
Being tested: Cingal, Triamcinolone Hexacetonide (TH), Placebo
Medical subject headings: Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CingalDrug
Also called HA + TH
Single intra-articular injection of Cingal into the knee.
Triamcinolone Hexacetonide (TH)Drug
Also called TH
Single intra-articular injection of TH into the knee.
PlaceboDrug
Also called Saline
Single intra-articular injection Placebo (0.9% Saline) into the knee.

Study groups in NCT04231318
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Triamcinolone Hexacetonide (TH)
Placebo	Placebo comparator	Single injection of Placebo: 4 milliliter (mL) dose of 0.9% saline. Manufactured by Anika Therapeutics. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 1 Week

Secondary outcomes (9)

The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index
The post-treatment responder rate 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 to treatment. 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 of the following three categories: pain, physical function, and patient's global assessment.
A higher percentage of subjects responding indicates a better outcome.
OMERACT-OARSI responder rates were compared between the Cingal, TH and Placebo arms.
Measured: 26 Weeks
Change From Baseline in Knee Pain as Measured by Visual Analog Scale (VAS) Pain Score
Change in knee pain was obtained from participant responses using a 100 mm Visual Analog Scale (VAS) Pain Score at each time point. This VAS scale ranged from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative value for the change in pain indicates less pain post-treatment. A larger negative value indicates a higher level of improvement, and a better outcome.
Measured: 26 Weeks
Change From Baseline in Knee Pain as Measured by Numerical Rating Scale (NRS) Pain Score
Change in knee pain was obtained from participant responses using a Numerical Rating Scale (NRS) Pain Score. This NRS Pain Score ranged from 0 = No Pain to 10 = Highest Pain Level. A negative value for the change in Pain Score indicates less pain post-treatment. A larger negative value indicates a higher level of improvement, and a better outcome.
Measured: 26 Weeks
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Score
The change from Baseline in knee function post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function Score comparing the Cingal, TH, and Placebo arms. WOMAC Function Score records participant responses regarding the difficulty they have performing daily activities. The WOMAC Function Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Difficulty to 100 mm = Extreme Difficulty. A negative value for the change from Baseline indicates improvement in WOMAC Function Score. A larger negative value indicates improvement in performing daily activities, and a better outcome.
Measured: 26 Weeks
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Score
The change from Baseline in knee stiffness post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score comparing the Cingal, TH, and Placebo arms. WOMAC Stiffness Score records participant responses regarding the sensation of ease in moving their joint. The WOMAC Stiffness Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Stiffness to 100 mm = Extreme Stiffness. A negative value for the change from Baseline indicates improvement in WOMAC Stiffness Score. A larger negative value indicates less stiffness, and a better outcome.
Measured: 26 Weeks
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score
The change from Baseline in overall clinical improvement in the knee post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score comparing the Cingal, TH, and Placebo arms. WOMAC Total Score combines the three 0-to-100 point scores from the WOMAC Pain Score, the WOMAC Stiffness Score, and the WOMAC Function Score to calculate a TOTAL Score from 0 = No Symptoms to 100 = Highest Degrees of Pain, Stiffness and Functional Limitation Symptoms.
A negative value for the change from Baseline in WOMAC Total Score indicates reduction in pain, stiffness, and improved function. A larger negative value indicates a better overall clinical outcome.
Measured: 26 Weeks
Change From Baseline in the Patient Global Assessment (PGA) Score
The change from Baseline in knee pain post-treatment as measured by the Patient Global Assessment (PGA) Score comparing the Cingal, TH, and Placebo arms. PGA Score records participant responses to their assessment of how much their STUDY (treated) knee is bothering them today . The PGA Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Extreme Pain.
A negative value for the change from Baseline indicates improvement in PGA Score. A larger negative value indicates less pain, and a better clinical outcome.
Measured: 26 Weeks
Change From Baseline in the Evaluator Global Assessment (EGA) Score
The change from Baseline in knee pain post-treatment as measured by the Evaluator Global Assessment (EGA) Score comparing the Cingal, TH, and Placebo arms. EGA Score records the Study Evaluator's assessment of how much the patient's STUDY (treated) knee is bothering them today . The EGA Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Extreme Pain.
A negative value for the change from Baseline indicates improvement in EGA Score. A larger negative value indicates less pain, and a better clinical outcome.
Measured: 26 Weeks
The Usage of Rescue Medication (Acetaminophen/Paracetamol) at 26 Weeks
The usage of Rescue Medication (RM) as based on the average number of acetominophen/paracetamol pills taken among participants at 26 Weeks post treatment comparing between the Cingal, Triamcinolone Hexacetonide (TH) and Placebo arms.
A smaller value in average RM indicates that fewer pills were taken by the participants, which may correlate to a better clinical outcome in terms of pain.
Measured: 26 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 202016 May 2022

First posted18 Jan 2020
Study start11 Sep 2020
Primary completion16 May 2022
Study completion16 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 231 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04231318
Sponsor's protocol ID: Cingal 19-01
Status last verified: Jun 2023
First submitted: 14 Jan 2020
Last updated: 9 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04231318
Acronym / sponsor ID: Cingal 19-01
Conditions: Osteoarthritis, Knee
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 231 participants (actual)
Lead sponsor: Anika Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 11 Sep 2020 (actual)
Primary completion: 16 May 2022 (actual)
Study completion: 16 May 2022 (actual)
First posted: 18 Jan 2020 (actual)
Results: Posted 9 Aug 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

A saline placebo is included within the trial to set the expectation of a return to Baseline pain for the subjects.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Cingal	Experimental	Drug: CingalSingle 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.
Triamcinolone Hexacetonide (TH)	Active comparator	Drug: Triamcinolone Hexacetonide (TH)Single injection of Triamcinolone Hexacetonide (TH): 1 milliliter (mL) dose of 20 mg/ml TH. Manufactured by IntraPharm.
Placebo	Placebo comparator	Drug: PlaceboSingle injection of Placebo: 4 milliliter (mL) dose of 0.9% saline. Manufactured by Anika Therapeutics.

Who may qualify

Ages: 40 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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:
Subject must be willing to abstain from other IA treatments of the knee for the duration of the study.

Key exclusion criteria (26 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CingalAlso: HA + THSingle intra-articular injection of Cingal into the knee.	Drug	Cingal
Triamcinolone Hexacetonide (TH)Also: THSingle intra-articular injection of TH into the knee.	Drug	Triamcinolone Hexacetonide (TH)
PlaceboAlso: SalineSingle intra-articular injection Placebo (0.9% Saline) into the knee.	Drug	Placebo

Primary outcome

Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
Time frame: 26 Weeks
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.
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
Time frame: 18 Weeks
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.
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
Time frame: 12 Weeks
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.
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
Time frame: 6 Weeks
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.
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score
Time frame: 3 Weeks
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.
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.

9 secondary outcomes

The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index
Time frame: 26 Weeks
Change From Baseline in Knee Pain as Measured by Visual Analog Scale (VAS) Pain Score
Time frame: 26 Weeks
Change From Baseline in Knee Pain as Measured by Numerical Rating Scale (NRS) Pain Score
Time frame: 26 Weeks
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Score
Time frame: 26 Weeks
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Score
Time frame: 26 Weeks
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score
Time frame: 26 Weeks
Change From Baseline in the Patient Global Assessment (PGA) Score
Time frame: 26 Weeks
Change From Baseline in the Evaluator Global Assessment (EGA) Score
Time frame: 26 Weeks
The Usage of Rescue Medication (Acetaminophen/Paracetamol) at 26 Weeks
Time frame: 26 Weeks

Results and safety

Results posted to the registry on 9 Aug 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cingal	99	99
Triamcinolone Hexacetonide (TH)	99	99
Placebo	33	33

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

Time frame: 26 Weeks. Mean (Standard Deviation). Unit: score on a scale

Measure	Cingal n = 99	Triamcinolone Hexacetonide (TH) n = 99	Placebo n = 33
Value	-44.3 (21.6)	-37.5 (22.9)	-36.1 (27.8)

Cingal vs Triamcinolone Hexacetonide (TH): p = 0.0406, ANOVA
Cingal vs Placebo: p = 0.0795, ANOVA
Triamcinolone Hexacetonide (TH) vs Placebo: p = 0.7601, ANOVA

Population analysed: Intent To Treat (ITT)

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

Time frame: 18 Weeks. Mean (Standard Deviation). Unit: score on a scale

Measure	CINGAL n = 99	Triamcinolone Hexacetonide (TH) n = 99	Placebo n = 33
Value	-44.5 (21.0)	-40.2 (23.0)	-36.7 (27.0)

CINGAL vs Triamcinolone Hexacetonide (TH): p = 0.1942, ANOVA
CINGAL vs Placebo: p = 0.0957, ANOVA
Triamcinolone Hexacetonide (TH) vs Placebo: p = 0.4526, ANOVA

Population analysed: Intent To Treat (ITT)

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

Time frame: 12 Weeks. Mean (Standard Deviation). Unit: score on a scale

Measure	Cingal n = 99	Triamcinolone Hexacetonide (TH) n = 99	Placebo n = 33
Value	-44.1 (22.4)	-38.9 (24.5)	-37.4 (25.6)

Cingal vs Placebo: p = 0.1309, ANOVA
Cingal vs Placebo: p = 0.1700, ANOVA
Triamcinolone Hexacetonide (TH) vs Placebo: p = 0.7609, ANOVA

Population analysed: Intent To Treat (ITT)

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

Time frame: 6 Weeks. Mean (Standard Deviation). Unit: score on a scale

Measure	Cingal n = 99	Triamcinolone Hexacetonide (TH) n = 99	Placebo n = 33
Value	-46.0 (23.0)	-40.4 (24.1)	-36.2 (25.1)

Cingal vs Triamcinolone Hexacetonide (TH): p = 0.1000, ANOVA
Cingal vs Placebo: p = 0.0423, ANOVA
Triamcinolone Hexacetonide (TH) vs Placebo: p = 0.3830, ANOVA

Population analysed: Intent To Treat (ITT)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cingal	1 of 99 (1%)	58 of 99 (58.6%)	0 of 99
Triamcinolone Hexacetonide (TH)	1 of 99 (1%)	29 of 99 (29.3%)	0 of 99
Placebo	0 of 33 (0%)	5 of 33 (15.2%)	0 of 33

Limitations and caveats (from the sponsor): There were no limitations or caveats associated with the conduct of this trial.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Joanne MacFie study director

Anika Therapeutics

26 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cingal and Triamcinolone Hexacetonide (TH) in people with Osteoarthritis, Knee, run by Anika Therapeutics, Inc. at 26 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score (time frame: 26 Weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04231318.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2023.