ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03281837
Previous Study | Return to List | Next Study

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03281837
Recruitment Status : Recruiting
First Posted : September 13, 2017
Last Update Posted : February 8, 2018
Sponsor:
Information provided by (Responsible Party):
Fidia Pharma USA Inc.

Brief Summary:

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 a 6 month period. The duration of the trial per center will be approximately 15 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.


Condition or disease Intervention/treatment Phase
Osteoarthritis, Knee Knee Osteoarthritis Patellofemoral Osteoarthritis Device: HYMOVIS plus Physical Exercise Program (PEP) Other: Physical Exercise Program (PEP) alone Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

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 HYMOVIS injections combined with a physical exercise program (PEP) to 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 a 6 month period. The duration of the trial per center will be approximately 15 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.

Masking: Double (Investigator, Outcomes Assessor)
Masking Description: This is a single-blind study. There will be a blinded evaluator who will not be informed about the intervention (Hymovis + PEP or PEP alone) to which study subjects will be randomized
Primary Purpose: Treatment
Official Title: A Post-market, Single Blind, Multicenter, Randomized, Controlled Trial of HYMOVIS® Intra-articular Injections in Active Subjects With Knee Osteoarthritis
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Group 1: Hymovis plus Physical Exercise Program (PEP)
Intra-articular (IA) Hyaluronan (HA) (Hymovis 24mg/3mL) combined with Physical Exercise program (PEP)
Device: HYMOVIS plus Physical Exercise Program (PEP)
1 injection of intra-articular (IA) hyaluronan (HA), Hymovis 24mg/3ml, injection per week for 2 weeks combined with at least 8 weeks of Physical Exercise Program (PEP)

Group 2: Physical Exercise Program (PEP) alone alone
Specified designed Physical Exercise Program (PEP) not combined with any other intervention
Other: Physical Exercise Program (PEP) alone
Physical Exercise Program (PEP) alone for at least 8 weeks

Group 3: Cross-Over group
Patients who were randomized to receive only Physical Exercise Program (PEP) alone and do not respond after 3 months to this intervention will have the opportunity to cross-over to receive 2 intra-articular weekly injections, each injection given 1 week apart, of Hymovis.
Device: HYMOVIS plus Physical Exercise Program (PEP)
1 injection of intra-articular (IA) hyaluronan (HA), Hymovis 24mg/3ml, injection per week for 2 weeks combined with at least 8 weeks of Physical Exercise Program (PEP)




Primary Outcome Measures :
  1. Improvement in average score for 4 of the 5 Knee Injury and Osteoarthritis Outcome Score subscales (KOOS) over 3 months from baseline (Day 90). Scores to be measured are pain, symptoms, function in sport and recreation, and knee related quality of life. [ Time Frame: Baseline and 90 days after baseline ]

Secondary Outcome Measures :
  1. Safety - Number of participants with intervention / treatment-related adverse events [ Time Frame: Baseline, 30 days, 60 days, 90 days, 120 days, 150 days, 180 days, through study completion (1 year) ]
    The investigator's determination and term of each adverse event (AE) will be mapped to system organ class and preferred term using the MedDRA dictionary. Incidence and frequency of AE's will be summarized for each treatment group by MedDRA system organ class and preferred term. A subject will only be counted once per system organ class and once per preferred term within a treatment. The summaries will include: All adverse events, All adverse events by severity, All adverse events by relationship to the study device, All adverse device effects, All adverse events leading to discontinuation from study

  2. Time to onset and duration of pain relief at all post-baseline points for the duration of the study [ Time Frame: Baseline, 30 days, 60 days, 90 days, 120 days, 150 days, 180 days, through study completion (1 year) ]
  3. Number of subjects achieving pain-free or disability-free return to sports over the duration of the study [ Time Frame: Baseline, 30 days, 60 days, 90 days, 120 days, 150 days, 180 days, through study completion (1 year) ]
  4. Analysis on the need for rescue analgesic medication for pain relief [ Time Frame: Baseline, 30 days, 60 days, 90 days, 120 days, 150 days, 180 days, through study completion (1 year) ]
  5. Global assessments and SF-12 conducted by the clinicians and self-reported by the subjects [ Time Frame: Baseline, 90 days, 180 days, through study completion (1 year) ]
  6. Number of subjects continuing to cross-over phase of study due to failure to respond adequately to PEP alone [ Time Frame: Baseline, 90 days, 180 days, through study completion (1 year) ]
  7. Biochemical serum biomarker analysis. [ Time Frame: Baseline, 90 days, 180 days, through study completion (1 year) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥21 years and ≤55 years old and with BMI ≤40
  • Moderate to severe knee OA pain ≥4 and ≤8 on the NRS pain subscale in the affected knee (signal knee)
  • Mild or no pain ≤2 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,
    2. lateral view of both the tibiofemoral and patellofemoral joints
    3. Merchant X-ray 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 view

Exclusion Criteria:

  • Radiographic assessment confirms abnormal patellofemoral tracking or articulation in lateral and/or Merchant 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 3 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.
  • 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 prescribed medicinal marijuana.
  • 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.
  • Participation in an experimental drug/device study or any clinical trial within the previous 90 days 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03281837


Contacts
Contact: Fidia Pharma USA Inc. 9735075123 medical@fidiapharma.us
Contact: Fidia Pharma USA Inc. 9735776202 medicaloffice@fidiapharma.us

Locations
United States, California
Kerlan-Jobe Orthopaedic Clinic Recruiting
Los Angeles, California, United States, 90045
Contact: Karen Mohr    310-665-7129    Karen.Mohr@kerlanjobe.com   
Contact: Josh Page    310-423-3198    Josh.Page@cshs.org   
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Denice Dubuclet    310-423-6996    denice.dubuclet@cshs.org   
Contact: Josh Page    310-423-3198    Josh.Page@cshs.org   
Horizon Clinical Research / Grossmont Orthopaedic Medical Group Recruiting
San Diego, California, United States, 91942
Contact: Marisa Radeke    619-456-6012    marisa@horizontrials.com   
Contact: Mona Hacker, MD    619-456-6012      
United States, Florida
Andrews Institute Orthopaedics and Sports Medicine - Andrews Research & Education Foundation Recruiting
Gulf Breeze, Florida, United States, 32561
Contact: Chelsea Gebs-Black    850-916-8570    chelsea.gebs@andrewsref.org   
Contact: Cassidy Shefferd    850-916-8592    cassidy.shefferd@andrewsref.org   
United States, New York
New York University - Center for Musculoskeletal Care Recruiting
New York, New York, United States, 10016
Contact: Ariel Aponte, CCRC    212-460-0176    ariel.aponte@nyumc.org   
Contact: Ivelisse Rodriguez Pagan    212-598-2311    ivelisse.pagan@nyumc.org   
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Katelyn Gasik    646-714-6436    gasikk@HSS.EDU   
United States, Virginia
IntegraTrials LLC / OrthoVirginia Recruiting
Arlington, Virginia, United States, 22205
Contact: Deborah Tominack, RN, CCRC    703-528-0385    trialsva@erols.com   
Sponsors and Collaborators
Fidia Pharma USA Inc.
Investigators
Principal Investigator: Cedars-Sinai Medical Center Cedars-Sinai Medical Center - Department of Orthopaedic Surgery
Principal Investigator: Kerlan-Jobe Orthopaedic Clinic Kerlan-Jobe Orthopaedic Clinic

Responsible Party: Fidia Pharma USA Inc.
ClinicalTrials.gov Identifier: NCT03281837     History of Changes
Other Study ID Numbers: EQE7-16-01
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Fidia Pharma USA Inc.:
osteoarthritis
knee osteoarthritis
patellofemoral osteoarthritis
tibiofemoral osteoarthritis
hyaluronan
hyaluronic acid
intra-articular
arthritis
joint disease
active
viscosupplements
Hymovis

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Hyaluronic Acid
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Viscosupplements
Protective Agents