2 Weekly Intra-articular Hyaluronan Knee Injections, Given 1 wk. Apart, of HYMOVIS Combined With Physical Exercise Program (PEP) Compared to PEP Alone, in Relatively Young, Active Population of Subjects With Patellofemoral Osteoarthritis (PFOA) and/or Tibiofemoral Osteoarthritis (TFOA)

Status:	Recruiting
Conditions:	Arthritis, Arthritis, Arthritis, Osteoarthritis (OA)
Therapuetic Areas:	Rheumatology
Healthy:	No
Age Range:	21 - 60
Updated:	7/27/2018
Start Date:	October 1, 2017
End Date:	December 2019
Contact:	Fidia Pharma USA Inc.
Email:	medical@fidiapharma.us
Phone:	9735075123

A Post-market, Single Blind, Multicenter, Randomized, Controlled Trial of HYMOVIS® Intra-articular Injections in Active Subjects With Knee Osteoarthritis

Knee osteoarthritis (OA) is among the most common causes of musculoskeletal pain and
disability. At present, there is no cure for OA. Therefore, the primary aims of therapy are
to reduce pain, maintain or improve function and mobility, and prevent or slow the
progression of adverse changes to the joint tissues, while keeping potential therapeutic
toxicities to a minimum. Current treatment guidelines begin with non-pharmacologic
modalities, such as patient education, weight loss, and physical therapy. Several
exercise-based therapeutic approaches, such as aerobic exercise programs, range-of-motion
exercises, and muscle-strengthening exercises are recommended and have shown clinical benefit
in randomized, controlled clinical trials. However, non-pharmacologic approaches frequently
provide insufficient pain relief and restoration of function and mobility, and pharmacologic
modalities become necessary. Although simple analgesics such as acetaminophen provide relief
for many OA subjects with mild to moderate pain, alternatives should be considered for
subjects who fail to obtain adequate symptomatic relief with these measures.

This post-market, single blind, multicenter, randomized, controlled clinical study is
designed to enroll a relatively young, active population of subjects with patellofemoral
osteoarthritis (PFOA) and/or tibiofemoral osteoarthritis (TFOA), and to compare responses to
treatment with 2 weekly intra-articular (IA) hyaluronan (HA) injections, with each injection
given 1 week apart, of HYMOVIS combined with a physical exercise program (PEP) to PEP alone.
Because PEP or exercise programs may be considered the first line standard of care in OA knee
pain, particularly in younger, active patients, the hypothesis of the study is that Hymovis
combined with PEP program provides greater relief of pain associated with knee OA in the
enrolled study subjects than with use of PEP alone.

The study provides for subjects randomized to the PEP alone study group to cross over to
HYMOVIS+PEP if improvement has not been achieved by the 3 month follow up visit.

Subjects will be recruited over an 18 month period. The duration of the trial per center will
be approximately 27 months. This includes the enrollment period of 6 months, the follow-up
period at 3 and 6 months and the additional follow-up period for patients who crossed-over;
they will be followed for an additional 6 months following the initial 3month follow-up. The
trial will end when the last subject makes the last visit.

Inclusion Criteria:

- Male or female ≥21 years and ≤60 years old and with BMI ≤40

- Moderate to severe knee OA pain ≥3 and ≤8 on the NRS pain subscale in the affected
knee (signal knee)

- Mild or no pain ≤3 on the numeric rating scale (NRS) pain subscale in the
contralateral knee (unaffected knee)

- Persistent knee pain lasting at least 3 months prior to Screening

- Active life-style (play or train themselves at least 2 to 3 times per week)

- Diagnosis of knee OA confirmed by radiographic assessment (must be performed within 6
months prior to screening visit):

1. anterior-posterior view (weight bearing extension or semi-flexion) of
tibiofemoral joint, (posterior-anterior/Rosenberg view as an additional
alternate)

2. lateral view of both the tibiofemoral and patellofemoral joints

3. Merchant X-ray (or Sunrise) view for patellofemoral joint.

- Radiographic assessment must confirm K-L Grade 1 to 3 for TFOA and/or K-L Grade 1 to
for PFOA.

- Radiographic assessment confirms normal articulation of patella and trochlea in
Merchant (or Sunrise) view

Exclusion Criteria:

- Radiographic assessment confirms abnormal patellofemoral tracking or articulation in
lateral and/or Merchant view (or Sunrise View)

- Major injury to or disorder of the contralateral knee or other weight-bearing joint
that would interfere with the study assessments.

- Secondary OA of the study joint due to a prior or concomitant condition (e.g., septic
arthritis, inflammatory joint disease, gout, articular fracture, major dysplasia, or
congenital abnormality, hemochromatosis, etc.).

- Surgery to the study joint within the previous 12 months prior to Screening. Surgery
to the contralateral knee or other weight-bearing joint within the previous 12 months
that would interfere with the study assessments.

- Patients with either total joint replacement implants, unicondylar implants or
patellofemoral replacement implants in the affected joint.

- Ligament reconstruction of the affected knee within 3 years.

- Inflammatory arthropathies such as rheumatoid arthritis, lupus, or psoriatic
arthritis.

- Episode of gout or calcium pyrophosphate (pseudogout) diseases within 6 months prior
to Screening.

- IA or local peri-articular corticosteroid injections to the study joint/knee within 8
weeks (2 months) prior to Screening or to any other joint (other than the study joint)
or soft tissue area within 1 month prior to Screening.

- Any oral corticosteroid within 1 month prior to Screening. Steroid inhalants are
permitted if the Subject has been on a stable regimen for the past 1 month prior to
Screening and remains on this regimen throughout the course of the trial.

- Intra-articular HA in the study joint within 6 months prior to Screening.

- History of allergic reaction to an intra-articular Hyaluronic acid injection.

- Known hypersensitivity (allergy) to gram positive bacterial proteins.

- Use of glucosamine or chondroitin sulfate containing products unless the subject is on
stable doses for at least 14 days prior to Screening and willing to remain on these
stable doses throughout the course of the study.

- Inability to perform the climbing stair test.

- X-ray findings of acute fractures, severe loss of bone density, avascular necrosis
and/or severe deformity.

- Axial deviation of the lower limbs greater than 20 degrees in valgus or varus on
standing X-ray.

- Symptomatic OA of either hip or spine with a pain score ≥2 on the NRS on or off pain
medication.

- Clinically significant medio-lateral and/or anterior-posterior instability.

- Osteonecrosis of either knee.

- Participation in a physical therapy regimen that has not been stable during the 1
month prior to Screening and the subject is unwilling or unable to maintain the same
regimen throughout the course of the trial or is unwilling to stop previously
prescribed or self-initiated physical therapy regimen and switch solely to and
initiate study defined PEP program.

- K-L Grade 4 TFOA of the knee (i.e., large osteophytes, marked narrowing, severe
sclerosis, and definite deformity).

- K-L Grade 4 PFOA of the knee (i.e., large osteophytes, marked narrowing, severe
sclerosis, definite deformity)

- Hemiparesis of the lower limbs.

- Significant surgery of lower limbs (hip, ankle, foot) that may interfere with knee
assessments.

- Chronic use of analgesia for pain (including pain in the other knee or any other
joint) that may interfere with the evaluations of the test knee (such as possible use
of rescue medication for these other conditions).

- Known allergies to acetaminophen and hyaluronan preparations.

- Know hypersensitivity (allergy) to anesthetics

- Recurrent medical history of severe allergic or immune-mediated reactions.

- Active infection or skin diseases in the area of the potential injection site or
joint.

- Any dermatological disease overlying the signal joint that would contraindicate
multiple injections or aspirations.

- Use of any agent reported to have symptom relief for arthritis or be a
disease/structure modifying drug (e.g. doxycycline, long-term tetracycline,
s-adenosylmethionine [SAM], methylsulfonylmethane [MSM] or dimethylsulfoxide [DMSO],
dietary supplements or any herbal remedy taken for arthritic and joint conditions
within the past month (exceptions as specified in Exclusion #14).

- Peripheral neuropathy that would be severe enough to interfere with the evaluation of
the subject.

- Psychological status (e.g., anxiety, depression, poor sleep quality, pain
catastrophizing, etc.) that may interfere with functional assessment of the target
knee.

- Vascular insufficiency of lower limbs that is severe enough to interfere with the
evaluation of the subject.

- Concomitant therapy with anticoagulants (low dose aspirin, not exceeding 325 mg per
day as an anti-thrombotic agent is permitted if stable for 1 month prior to Screening
and remains stable throughout the study).

- Any concomitant disease(s) or condition(s) that may interfere with the free use and
evaluation of the affected knee for the 6 months course of the trial (cancer, other
rheumatic diseases, gout, severe congenital defects, etc.).

- Any serious mobility problems (e.g. Parkinson's disease) or claustrophobia

- Any concomitant chronic disease(s) or condition(s) that may predispose them to a high
probability of interfering with the completion of the 6-month follow-up of the study
such as peptic ulcer, liver disease, severe coronary disease, renal disease, cancer,
pregnancy, alcoholism, drug abuse, mental state, or other clinically significant
condition.

- Excessive alcohol consumption or alcoholism that would be contraindicated with the use
of acetaminophen.

- Use of marijuana, whether prescribed or not

- Any clinically significant diagnostic test and/or abnormal laboratory test result(s)
that, in the opinion of the clinical investigator, may place the subject's health at
risk, impact the study, or impact the subject's ability to complete the study.

- Inability to legally comprehend the details and nature of the study for any reason,
including psychiatric illness.

- Likelihood of protocol violations or unlikely to compete the study for any reason, as
determined by the clinical investigator.

- Continued participation in an experimental drug/device study or any clinical trial
within the previous 8 weeks prior to Screening. Subjects must have fully completed
participation in an experimental drug/device study of any clinical trial at least 8
weeks prior to screening.

- Pregnancy, breastfeeding, planned conception, premenopausal women who have not had
tubal ligation, hysterectomy, or are unwilling or unable to utilize contraceptive
measures (or contraception)

- Prior history of any malignancy with the exception of basal cell carcinoma of the skin
treated more than 2 years prior to Screening.

- Significant bleeding diathesis.

- Participation in current litigation for injuries related to the study knee or other
injuries that might interfere with their completion of the study protocol.

- Non-English speaking subjects.

We found this trial at

sites

Cedars-Sinai Medical Center

8700 Beverly Blvd # 8211
Los Angeles, California 90048

(1-800-233-2771)