Study of Cingal™ for the Relief of Knee Osteoarthritis Compared to Triamcinolone Hexacetonide

NCT03191903 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 1 other identifier: Cingal 16-02
• Study Type: interventional
• Target: 576
• Locations: 2 countries
• Sites: 19

Brief Summary

This is a multi-center, randomized, double-blind, parallel group, active comparator controlled trial to evaluate the efficacy and safety of a single injection of Cingal for the relief of joint pain in subjects with OA of the knee.

Conditions

Knee Osteoarthritis

Keywords

Osteoarthritis; Intra-articular Injection; Hyaluronic Acid; Triamcinolone Hexacetonide

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in WOMAC Pain Score at 26 Weeks (ITT Population)

  The change from baseline in knee pain as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal group to the TH group. The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the change from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

  26 weeks

Secondary Outcomes (9)

• Change From Baseline in WOMAC Pain Score at 3 Weeks (ITT Population)

  3 weeks

• OMERACT-OARSI Responder Index at 26 Weeks Post Treatment Comparing the Cingal Group to the TH Group (ITT Population)

  26 weeks

• Change From Baseline in WOMAC Physical Function Score at 26 Weeks (ITT Population)

  26 weeks

• Change From Baseline in WOMAC Stiffness Score at 26 Weeks (ITT Population)

  26 weeks

• Change From Baseline in Total WOMAC Score at 26 Weeks (ITT Population)

  26 weeks

Other Outcomes (1)

• Change From Baseline in WOMAC Pain Score at 3 Weeks in the Per-Protocol Population

  3 Weeks

Study Arms (3)

Cingal

EXPERIMENTAL

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

Combination Product: Cingal

Monovisc

ACTIVE COMPARATOR

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

Triamcinolone Hexacetonide (TH)

ACTIVE COMPARATOR

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

Drug: Triamcinolone Hexacetonide

Interventions

Cingal COMBINATION_PRODUCT

Hyaluronic Acid with Triamcinolone Hexacetonide

Also known as: HA + TH

Cingal

Monovisc DEVICE

Hyaluronic acid

Also known as: HA

Monovisc

Triamcinolone Hexacetonide DRUG

Triamcinolone Hexacetonide

Also known as: TH

Triamcinolone Hexacetonide (TH)

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, 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.
• Subject has had at least two signs and at least two symptoms of OA disease (based on the European League Against Rheumatism (EULAR) recommendations for diagnosing knee OA) in the index knee for at least 6 months despite conservative treatment (weight reduction, physical therapy, pain medications, etc.). The EULAR signs and symptoms are as follows:
• Signs: crepitus, restricted movement and bony enlargement
• Symptoms: persistent knee pain, limited morning stiffness and reduced function
• Subject must be willing to abstain from other IA treatments of the knee for the duration of the study.
• Subject is willing to discontinue all analgesics including NSAIDs, except acetaminophen/paracetamol, at least seven days before the treatment injection and through the completion of the study.
• Subject is willing to use only acetaminophen/paracetamol (up to a maximum of 4.0 grams per day per the package insert) for the treatment of joint pain for the duration of the study. At least forty eight hours prior to the Baseline Visit and each follow-up visit, the subject is willing to discontinue use of acetaminophen/paracetamol.
• Subject is willing to maintain a stable dose of oral glucosamine and/or chondroitin sulfate products throughout the study, if taken prior to signing the informed consent form (ICF).
• 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 informed consent form (ICF). A subject will be excluded if they are planning to receive an HA or steroid injection (other than the study injection) in either knee during the course of this study.
• Subject had an arthroscopy of either knee within 3 months of signing the ICF.
• Subject had an open surgical procedure of either knee or hip or any surgery of the spine within 12 months of signing ICF. Subject plans to have knee, hip or spine surgery within the study period.
• Subject has intra-articular trauma to the index knee. Subject has concurrent multi-system or multi-limb trauma.
• Subject has evidence or medical history of the following diseases in the index knee: septic arthritis; inflammatory joint disease; history of Reiter's syndrome; gout; chondrocalcinosis associated with recurrent episodes of acute synovitis of the knee consistent with pseudogout; osteochondritis dissecans, Paget disease of the bone; ochronosis; acromegaly; hemochromatosis; primary osteochondromatosis; known history of Wilson disease; heritable disorders or collagen gene mutations.
• Subject has a history of cartilage repair surgery in the index knee within 3 years of signing the ICF.
• Subject has a history of ACL repair, reconstruction or injury in the index knee within 3 years of signing the ICF.
• Subject has X-ray findings of acute fractures, severe bone loss, avascular necrosis, severe bone or joint deformity in the index knee.
• Subject has significant varus or valgus deformity greater than 10 degrees in either knee.
• Subject has a clinically apparent tense effusion of the index knee.
• 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 HbA1c of \>7%.
• 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 (19)

Health Center of Downtown-Lipotvaros, Orthopedic Outpatient Clinic (Belvárosi-Lipótvárosi Egészségügyi Szolgálat Ortopeadia)

Budapest, 1051, Hungary

Location

Magyar Honvedseg

Budapest, 1134, Hungary

Location

Uzsoki Utcai Kórház

Budapest, 29-41, Hungary

Location

Baleseti Központ

Budapest, Hungary

Location

DE KK Ortopediai Klinika

Debrecen, Hungary

Location

Jutrix Medical Llc

Kecskemét, 6000, Hungary

Location

Medidea Bt.

Kiskunfélegyháza, 6100, Hungary

Location

Kastelypark Klinka

Tata, 2890, Hungary

Location

Zdrowie Osteo-Medic

Bialystok, Poland

Location

Szpital Świętego Łukasza S.A.

Bielsko-Biala, Poland

Location

NZOZ Medi SPATZ

Gliwice, Poland

Location

ARTIMED Niepubliczny Zakład Opieki Zdrowotnej

Kielce, Poland

Location

Centrum Medyczne 4M Plus

Krakow, Poland

Location

Medical University of Lodz

Lodz, Poland

Location

Lubelskie Centrum Diagnostyczne

Świdnik, Poland

Location

NOVAMED Jackowiak Krajewski Spółka Jawna

Torun, Poland

Location

Centrum Medyczne Amed Warszawa Targówek

Warsaw, Poland

Location

ETG Network, Warsaw

Warsaw, Poland

Location

ETG Network

Warsaw, Poland

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

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

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

Cingal 16-02 did not include a placebo arm, and was an all-active trial.

Results Point of Contact

• Title: Carol Pekar, VP Clinical Affairs
• Organization: Anika

cpekar@anikatherapeutics.com

781-457-9218

Study Officials

• Laszlo Hangody, MD

  Uzsoki Hospital, Department of Traumatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Study subjects and the Outcomes Assessor are blinded to the study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects are randomized in a 4:4:1 ratio into the Cingal, Monovisc (hyaluronic acid) or TH (triamcinolone hexacetonide) arms.

Study Record Dates

• First Submitted: June 16, 2017
• First Posted: June 19, 2017
• Study Start: May 25, 2017
• Primary Completion: April 23, 2018
• Study Completion: April 23, 2018
• Last Updated: February 24, 2022
• Results First Posted: February 24, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

HU (8); PL (11)