Osteoarthritis Ankle
Conditions
Keywords
Hyaluronic Acid
Brief summary
The goal of this study is to demonstrate the clinical improvement and safety in patients treated with MONOVISC for ankle osteoarthritis. Specifically, this study will provide confirmation to the effectiveness and safety of MONOVISC at relieving ankle joint pain to 6 months post-treatment.
Detailed description
Obtain real world, post market data to confirm the clinical improvement and safety in patients treated with a single injection of MONOVISC for the symptomatic relief of osteoarthritis in the ankle joint. The entire study duration from first subject in to last subject out will be approximately one and half years. The enrollment phase will be approximately 12 months with a follow-up phase of 6 months. Visits will be scheduled at screening, baseline, 1 month, 3 months and 6 months post treatment.
Interventions
DEVICEMonovisc
A chemically cross-linked sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe.
Sponsors
Anika Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older 2. Body Mass Index (BMI) ≤ 35 kg/m2 3. Diagnosis of symptomatic osteoarthritic joint in the index joint (Kellgren-Lawrence grade I to III) to be treated with MONOVISC injection. 4. Failed conservative treatment for joint osteoarthritis. 5. NRS pain on walking ≥4 and ≤9 in the index joint. 6. Subject must be willing to abstain from other treatments of the index joint for the duration of the study. 7. 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. 8. 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. 9. 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). 10. Able and willing to provide signed informed consent.
Exclusion criteria
1. History of hypersensitivity to any of the ingredients in the hyaluronan 2. Infection or skin disease in the area of the injection site or index joint 3. NRS pain on walking \> 3 in the contralateral joint 4. NRS pain on walking \> 3 in the ipsilateral knee or hip 5. Subject received an injection of Hyaluronic Acid (HA) and/or steroid in either joint 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 joint during the course of this study. 6. Known inflammatory or autoimmune disorders (including rheumatoid arthritis, gout), or other pre-existing medical conditions that, in the opinion of the investigator, could impact treatment of the index joint or affect the ability of the subject to accurately complete the study questionnaires and comply with the study requirements. 7. Subject is taking medications at the time of signing 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. 8. Subjects who had an oral, intramuscular, intravenous, rectal suppository or topical (excluded in index joint only) corticosteroid prior 30 days of signing the ICF are excluded. Topical corticosteroid use at any site other than the index joint is allowed. 9. Significant trauma to the index ankle within 26 weeks of screening 10. Chronic use of narcotics or cannabis. 11. Ligament instability or tear in index joint. 12. Chronic impingement in the index joint requiring surgical treatment 13. Diagnosis of fibromyalgia 14. Diagnosis of osteonecrosis in index joint 15. Subject has significant varus or valgus deformity greater than 10 degrees in either knee. 16. Subject requires consistent use of an assistive device (e.g. wheelchair, walker, etc.) Occasional use of a cane is acceptable. 17. Uncontrolled diabetes with HbA1c of \>7%. 18. 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. 19. Subject is receiving or in litigation for worker's compensation. 20. Otherwise determined by the investigator to be medically unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Rating Scale (NRS) Pain on Walking | Baseline to 6 Months | Mean Change in Numerical Rating Scale (NRS) Pain on Walking in the Index Ankle from baseline to 6 Months post injection. NRS is an 11-Point scale where 0=No Pain, 10=Worst Pain. A larger negative value (maximum -10.0) for the change from baseline indicates less pain and a better clinical outcome following treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American Orthopaedic Foot and Ankle Society (AOFAS) Score | Baseline to 6 Months | Mean Change from baseline to 6 months in the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Rating System Score. AOFAS is a standardized evaluation of the clinical status of the ankle-hindfoot. It incorporates both subjective and objective information in three parts to evaluate Pain, Function and Alignment. Patients report their pain (40 points), and function (50 points), and the evaluator assesses alignment (10 points). A total score is calculated by adding the three scores for final range from 0 (worst clinical status) to 100 points (best clinical status). A positive increase in value for the change in AOFAS score indicates improvement. A larger positive value indicates a higher level of improvement, and a better outcome. |
| Patient Global Assessment (PGA) Score | Baseline to 6 Months | Mean change from baseline to 6 months in ankle pain post-treatment as measured by the Patient Global Assessment (PGA) Score. PGA Score records participant responses to their assessment of how much their STUDY (treated) ankle is bothering them today. The PGA Score is a validated 11-point Likert scale from 0=No Pain to 10=Worst Pain. A negative value for the change from baseline indicates improvement in PGA Score. A larger negative value (maximum -10.0) for the change from baseline indicates less pain and a better clinical outcome following treatment. |
| The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index | 6 Months | The post-treatment responder rate is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index. The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder to treatment. The criteria for response are (1) improvement in pain or physical function \>50% and an absolute change \>20 mm; or (2) improvement of \>20% with an absolute change \>10 mm in at least of the following three categories: pain, physical function, and patient's global assessment. A higher percentage of subjects responding indicates a better outcome. |
| Number of Participants NOT Using Rescue Medication (Acetaminophen/Paracetamol) | 6 Months | The usage of Rescue Medication (RM) as based on the number of participants at 6 months post treatment that were NOT using acetaminophen/paracetamol RM for pain or discomfort. A larger percentage of participants that were NOT using RM may correlate to a better clinical outcome in terms of pain. |
Countries
Czechia, Poland
Participant flow
Pre-assignment details
Only one ankle \[Index Ankle\] of each participant was included in this study.
Participants by arm
| Arm | Count |
|---|---|
| MONOVISC Single injection of MONOVISC into the index ankle joint | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | MONOVISC |
|---|---|
| Age, Continuous | 52.16 years STANDARD_DEVIATION 14.26 |
| Index Ankle Left | 12 Participants |
| Index Ankle Right | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 4 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Numerical Rating Scale (NRS) Pain on Walking
Mean Change in Numerical Rating Scale (NRS) Pain on Walking in the Index Ankle from baseline to 6 Months post injection. NRS is an 11-Point scale where 0=No Pain, 10=Worst Pain. A larger negative value (maximum -10.0) for the change from baseline indicates less pain and a better clinical outcome following treatment.
Time frame: Baseline to 6 Months
Population: Intent To Treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monovisc | Numerical Rating Scale (NRS) Pain on Walking | -3.00 score on a scale | Standard Deviation 1.8 |
p-value: <0.0001t-test, 1 sided
Secondary
American Orthopaedic Foot and Ankle Society (AOFAS) Score
Mean Change from baseline to 6 months in the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Rating System Score. AOFAS is a standardized evaluation of the clinical status of the ankle-hindfoot. It incorporates both subjective and objective information in three parts to evaluate Pain, Function and Alignment. Patients report their pain (40 points), and function (50 points), and the evaluator assesses alignment (10 points). A total score is calculated by adding the three scores for final range from 0 (worst clinical status) to 100 points (best clinical status). A positive increase in value for the change in AOFAS score indicates improvement. A larger positive value indicates a higher level of improvement, and a better outcome.
Time frame: Baseline to 6 Months
Population: Intent To Treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monovisc | American Orthopaedic Foot and Ankle Society (AOFAS) Score | 16.08 score on a scale | Standard Deviation 13.27 |
p-value: <0.0001t-test, 1 sided
Secondary
Number of Participants NOT Using Rescue Medication (Acetaminophen/Paracetamol)
The usage of Rescue Medication (RM) as based on the number of participants at 6 months post treatment that were NOT using acetaminophen/paracetamol RM for pain or discomfort. A larger percentage of participants that were NOT using RM may correlate to a better clinical outcome in terms of pain.
Time frame: 6 Months
Population: Intent To Treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Monovisc | Number of Participants NOT Using Rescue Medication (Acetaminophen/Paracetamol) | 20 Participants |
Secondary
Patient Global Assessment (PGA) Score
Mean change from baseline to 6 months in ankle pain post-treatment as measured by the Patient Global Assessment (PGA) Score. PGA Score records participant responses to their assessment of how much their STUDY (treated) ankle is bothering them today. The PGA Score is a validated 11-point Likert scale from 0=No Pain to 10=Worst Pain. A negative value for the change from baseline indicates improvement in PGA Score. A larger negative value (maximum -10.0) for the change from baseline indicates less pain and a better clinical outcome following treatment.
Time frame: Baseline to 6 Months
Population: Intent To Treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monovisc | Patient Global Assessment (PGA) Score | -2.96 score on a scale | Standard Deviation 1.97 |
p-value: <0.0001t-test, 1 sided
Secondary
The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index
The post-treatment responder rate is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index. The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder to treatment. The criteria for response are (1) improvement in pain or physical function \>50% and an absolute change \>20 mm; or (2) improvement of \>20% with an absolute change \>10 mm in at least of the following three categories: pain, physical function, and patient's global assessment. A higher percentage of subjects responding indicates a better outcome.
Time frame: 6 Months
Population: Intent To Treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Monovisc | The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index | 21 Participants |