The purpose of this study is to evaluate the safety and performance of Hydros and Hydros with triamcinolone acetonide, (Hydros TA) for treatment of pain from osteoarthritis of the knee, in patients who have failed to respond adequately to…
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints
Effectiveness
WOMAC Pain Subscale Score
The WOMAC Pain Subscale is used to assess the severity of the knee pain at
Screening, Week 2 Follow-up, Week 6 Follow-up, Week 13 Follow-up, and Week 26
Follow-up visits. For each subject the scores of the five questions that
comprise the WOMAC Pain subscale are averaged.
The primary endpoint is the time-weighted change from baseline in the WOMAC
Pain sub-scale average score in the treatment knee.
Secondary analyses include the change from baseline to week 13 and change from
baseline to week 26.
Safety
The safety and tolerability of Hydros and Hydros TA will be evaluated by
comparison of Adverse Event (AE) rates. AEs will be followed through
resolution or 30 days after the subject terminates from the study, whichever
occurs first.
Secondary outcome
Secondary Endpoints
Positive Responders
The number and percentage of subjects who have a positive response based on the
OMERACT-OARSI set of responder criteria will be used to assess differences
between the treatment groups in response to treatment for symptomatic primary
OA of the knee over 26 weeks.
Paracetamol Usage
To assess differences in the amount of pain medication required over the
treatment period, the average daily dosage of paracetamol (grams) will be
assessed.
WOMAC Function Subscale Score
The WOMAC Function Subscale is used to assess the severity of the knee function
at Screening, Week 2 Follow-up, Week 6 Follow-up, Week 13 Follow-up, and Week
26 Follow-up visits. For each subject the scores of the five questions that
comprise the WOMAC Function subscale are averaged.
WOMAC Stiffness Subscale Score
The WOMAC Stiffness Subscale is used to assess the severity of the knee
function at Screening, Week 2 Follow-up, Week 6 Follow-up, Week 13 Follow-up,
and Week 26 Follow-up visits. For each subject the scores of the five
questions that comprise the WOMAC Stiffness subscale are averaged.
Background summary
Osteoarthritis (OA) is a common degenerative joint disease with 22 million men
and women in the European Union affected1. About 6% of the European population
age 30 and over have frequent knee pain and radiographic osteoarthritis. These
findings are comparable to studies which estimate that 21 million women and men
in the US who are 25 years and older (approximately 12.1%) are affected by OA
and more than 40% of all adults over 75 years old are affected. OA is the
leading cause of disability in Europe, the USA and Japan. Pain from
osteoarthritis has a major influence on a patient*s quality of life and carries
a heavy economic burden.
Osteoarthritis is characterized by loss of articular cartilage, subchondral
bone sclerosis, osteophyte formation, changes in the synovial membrane, and
reduced viscosity of synovial fluid.
There are limited options for treating pain associated with osteoarthritis.
Treatments range from measures that limit weight impact on the joints, to oral
analgesics and anti-inflammatory drugs, to steroid and viscosupplement
intra-articular (IA) injections, and surgical joint replacement. The European
League Against Rheumatism (EULAR) concludes that there is evidence to support
the efficacy of hyaluronan (viscosupplements) in knee OA, for pain reduction
and functional improvement, with greater length of time benefit than
intra-articular steroids. As such, hyaluronan is an effective IA
viscosupplementation therapy that is used to minimize pain and to facilitate
joint movement in patients with OA of the knee.
Hyaluronan is a naturally occurring constituent of the extracellular matrix of
body tissues and is found in significant concentration in the synovial fluid
and articular cartilage of joints. Hyaluronan functions by lubricating joints
and by aiding articular mobility, thereby reducing pain. Various hyaluronan
based products for intra-articular injection are now available and are used
commonly worldwide to treat OA of the knee.
Clinical trials for the treatment of knee OA with intra-articular hyaluronan
injection have been extensively analyzed and compared for their design and
outcomes. A systematic review of six meta-analyses of hyaluronan in
osteoarthritis of the knee show conflicting estimates of therapeutic effect;
however, in the balance between benefit to harm, the probable benefit of pain
reduction and physical function improvement outweighs the low risk of harm.
A meta-analysis of the literature on intra-articular corticosteroid injection
for OA of the knee extracted ten randomised and controlled trials from a search
of the Cochrane controlled trials register, Medline (1966 to 2003), and Embase
(1980 to 2003). This meta-analysis concluded that the evidence supports short
term (up to two weeks) improvement in symptoms of osteoarthritis of the knee
after intra-articular corticosteroid injection. Raynauld et al. studied the
safety of long-term (up to 2 years) intra-articular injection treatment with
triamcinolone acetonide (40mg) in OA of the knee. The study concluded that with
repeat intra-articular injections of triamcinolone acetonide every 3 months
there were no deleterious effects on the anatomical structures of the knee, as
measured by loss of joint space, at the one and two year follow-up
evaluations. Moreover long-term treatment of knee OA with repeated steroid
injections appears to be clinically effective for the relief of symptoms of the
disease.
Studies have also evaluated the concomitant use of hyaluronan with steroids,
anti-inflammatory drugs, and analgesic agents in an attempt to magnify the
extent and duration of pain relief. In a one year study of hyaluronan with and
without triamcinolone acetonide, both groups improved with the
combination-therapy subjects improving sooner. Other clinical studies have
successfully used steroids with hyaluronan for pain relief and consider this
combination treatment as complementary therapy.
Future studies of hyaluronan combined with steroid treatment will add to the
body of knowledge for management of OA of the knee. The Hydros product
combined with TA to be evaluated here has distinct potential advantages from a
safety and effectiveness standpoint.
Study objective
The purpose of this study is to evaluate the safety and performance of Hydros
and Hydros with triamcinolone acetonide, (Hydros TA) for treatment of pain from
osteoarthritis of the knee, in patients who have failed to respond adequately
to conservative non-pharmacologic therapy and simple analgesics, e.g.,
paracetamol (acetaminophen). A three arm study will compare Hydros and Hydros
TA, both investigational viscosupplements, to Synvisc-One, a commercially
available viscosupplement. Viscosupplementation is a therapeutic technique
that directly addresses the cause of pain, by replacing the low elastoviscous
osteoarthritic synovial fluid with high elastoviscous solutions of hyaluronan
or its derivatives. Triamcinolone acetonide, the steroid in Hydros TA, has been
a standard therapeutic treatment for OA joint pain for over 40 years.
Study design
Study Design
This study is a multi-center, controlled, randomized, double blind study. All
of the subjects will receive either Hydros, Hydros TA, or Synvisc-One injected
into one treatment knee joint. Hydros and Hydros TA are investigational
products (not approved for sale). The steroid component of Hydros TA
(triamcinolone acetonide) and Synvisc-One are approved products for joint
injection to treat pain related to osteoarthritis.
There will be four follow-up visits which will occur at 2 weeks, 6 weeks, 13
weeks, and 26 weeks after the injection. The procedures for the study are
explained in detail in this document.
Intervention
Hydros is an absorbable gel made of a naturally occurring substance (hyaluronic
acid). Hyaluronic acid (HA) is found in various tissues throughout the human
body, including the natural fluid in the knee. The HA raw material used to
manufacture Hydros is produced biosynthetically and contains no animal or human
components. The product is supplied as a single injection, ready to use, in a
10 mL glass syringe containing 6 mL of sterile Hydros at physiologic pH.
Hydros TA is an absorbable gel made of a naturally occurring substance
(hyaluronic acid), combined with a low dose, well-known steroid
(anti-inflammatory drug), triamcinolone acetonide (TA). Triamcinolone
acetonide is approved for injection into the knee joint to treat pain related
to osteoarthritis. Hydros TA is supplied as a single injection, ready to use,
in a 10 mL glass syringe containing 6 mL of sterile Hydros TA at physiologic pH.
Control material:
Synvisc-One (hylan G-F 20) is an elastoviscous high molecular weight fluid
containing hylan A and hylan B polymers produced from chicken combs. Hylans
are derivatives of hyaluronan (sodium hyaluronate). Hylan G-F 20 is unique in
that the hyaluronan is chemically crosslinked. The contents of the syringe are
sterile and non-pyrogenic. Synvisc-One is a single injection product that is
approved for use in Europe and the USA.
Study burden and risks
As with all medical procedures, there are risks involved. You may experience
side effects while in the study. Everyone taking part in the study will be
watched carefully for any side effects. However, doctors don*t know all the
side effects that may happen. Side effects may be mild or very serious. In
rare cases side effects can be serious and long lasting. Your doctor will
discuss the risks of this treatment with you.
The potential risks associated with the use of Hydros, Hydros TA and
Synvisc-One may include those events that have been reported in association
with other similar hyaluronan products. These risks include, but are not
limited to, the following: pain, swelling and/or effusion in the injected
knee, rash, hives, itching, fever, nausea, headache, dizziness, chills, muscle
cramps, paresthesia (numbness, tingling), peripheral edema (swelling in the
feet and legs).
Risks to subjects in this study may also include all the risks currently
associated with corticosteroid therapy, which includes conditions that affect
the following systems; fluid and electrolyte balance, musculoskeletal,
cardiovascular, neurologic, gastrointestinal, dermatologic, endocrine,
ophthalmic, metabolic and other areas.
3181 Porter Drive
Palo Alto, CA 94304
NL
3181 Porter Drive
Palo Alto, CA 94304
NL
Listed location countries
Age
Inclusion criteria
1. Osteoarthritis (OA) grade 2 or 3 in one knee using Kellgren-Lawrence Grading for OA radiologically and verified within the prior 6 months.
a. Grade 2 defined as definite osteophytes with unimpaired joint space
b. Grade 3 defined as definite osteophytes with moderate joint space narrowing
2. Treatment knee criteria:
a. WOMAC Pain subscale score of 50-90 mm on a Visual Analogue Scale (VAS) (where 0 <= no pain and 100 mm <= worst pain) for the average of the five pain questions, and
b. One WOMAC Pain subscale score allowed to be below 20 mm or above 90 mm on the VAS.
3. Non-treatment knee WOMAC Pain subscale score less than or equal to 30 mm average of the five pain questions.
4. Symptoms in the treatment knee for at least 12 months.
5. Fully ambulatory subject (ability to perform a 15 meters walk test).
6. Male and female subjects 40 through 85 years of age.
7. Willing to NOT take any pain medication for 48 hours prior to each study visit and provide a list of pain medications taken between visits.
NOTE: Subject may take the following during the study:
a. Up to a maximum of 4 gm. paracetamol (acetaminophen) daily for treatment knee pain.
b. Single daily low dose ASA up to 325 mg.
c. Short term (3 days or less) NSAIDs for pain of origin other than treatment knee.
8. Written consent to participate in the clinical study following subject*s review of the COR 1.0 Study Subject Information and Consent form.
9. Able to understand the requirements of the study and willing to comply with all treatment and study evaluations for the duration of the trial.
10. Females of childbearing potential must not be or become pregnant for the duration of the study.
Exclusion criteria
1. Non-treatment knee joint pain greater than 30 mm average WOMAC Pain subscale scores.
2. Secondary OA resulting from rheumatoid arthritis, chondrocalcinosis, osteonecrosis, chronic fibromyalgia or other autoimmune disease.
3. Generalized symptomatic OA in lower extremity joints other than the knees, inflammatory joint disease, bursitis, OA in the hips, or other condition that may interfere with study assessments. Diagnosis is from medical history or prior xrays. Upper extremity OA is NOT excluded.
4. Active infection in either knee joint or adjacent tissues or positive synovial fluid culture of any joint.
5. Any contraindications for intra-articular injection or aspiration.
6. Knee surgery or trauma within 3 months prior to enrollment or planned joint surgery for the period of study duration.
7. Intra-articular steroid injection in the knee and/or use of systemic (oral) corticosteroids within 3 months prior to enrollment. Inhaled steroids are NOT excluded.
8. Intra-articular hyaluronan injection in the treatment knee within 6 months prior to enrollment.
9. BMI greater than 35.
10. Known hypersensitivity/allergic/anaphylactic reactions to local anesthetics.
11. Known sensitivity to avian proteins, corticosteroids, or hyaluronan-based products.
12. Arthroscopy of either knee or in any other joint within one (1) month prior to enrollment.
13. Started the use of glucosamine, chondroitin sulfate, diacerhein, or avocado/soya extracts within 2 months prior to Screening.
14. Current treatment with systemic steroids, narcotic analgesics, acetylsalicylic acid (ASA) greater than 325 mg daily, NSAIDs, COX inhibitors, or joint creams (e.g. methylsalicylate or capsaicin).
NOTE: Subject may take the following during the study:
a. Up to a maximum of 4 gm. paracetamol daily for treatment knee pain.
b. Single daily low dose ASA up to 325 mg.
c. Short term (3 days or less) NSAIDs for pain of origin other than treatment knee.
15. Current uncontrolled diabetes mellitus.
16. Current use of intra-articular injections.
17. Clinically significant conditions that would interfere with accuracy of study evaluations, e.g. malignant neoplastic disease, intra-articular tumor, fibromyalgia, peripheral neuropathy, vascular insufficiency, hemiparesis, significant psychiatric or neurological disorders, active alcohol/drug abuse, or other factors that the investigator feels would interfere with study evaluations and study participation.
18. Participation in another clinical trial and/or treatment received with any investigational agent within 30 days before enrollment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL30855.018.10 |