Overview

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

Status:
Completed
Trial end date:
2018-04-23
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Anika Therapeutics, Inc.
Treatments:
Hyaluronic Acid
Triamcinolone
Triamcinolone Acetonide
Triamcinolone diacetate
Triamcinolone hexacetonide
Criteria
Inclusion Criteria:

- Screening Inclusion Criteria

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

2. 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.

3. 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

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

5. 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.

6. 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.

7. 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).

8. Subject is able to understand and comply with the requirements of the study and
voluntarily provides consent.

Exclusion Criteria:

- 1. 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.

2. Subject had an arthroscopy of either knee within 3 months of signing the ICF.

3. 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.

4. Subject has intra-articular trauma to the index knee. Subject has concurrent
multi-system or multi-limb trauma.

5. 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.

6. Subject has a history of cartilage repair surgery in the index knee within 3 years
of signing the ICF.

7. Subject has a history of ACL repair, reconstruction or injury in the index knee
within 3 years of signing the ICF.

8. Subject has X-ray findings of acute fractures, severe bone loss, avascular
necrosis, severe bone or joint deformity in the index knee.

9. Subject has significant varus or valgus deformity greater than 10 degrees in either
knee.

10. Subject has a clinically apparent tense effusion of the index knee. 11. Subject
has knee instability in either knee per the Investigator's assessment.

12. Subject requires consistent use of an assistive device (e.g. wheelchair, walker,
etc.) Occasional use of a cane is acceptable.

13. 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%.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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/paracetamol.

19. Subject has any contraindication to the receipt of a corticosteroid. 20. Subject
is receiving or in litigation for worker's compensation. 21. 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.

22. 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.

Baseline Inclusion Criteria

1. Subject has a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
pain-sub-score ≥ 40 mm and ≤ 90 mm in the affected knee and ≤ 30 mm in the contralateral
knee on a 100 mm Visual Analog Scale (VAS) scale.

Baseline Exclusion Criteria

1. 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.

2. Subject has a synovial fluid aspirate volume > 20 mL in the index knee.

3. 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).

4. Subject has range of motion of less than 100° flexion in either knee.