Knee Osteoarthritis
Conditions
Brief summary
This multicentre, prospective, randomized, double-blind, active-controlled, parallel group clinical investigation is aimed to assess the safety and the clinical performance over 6 months of a single intra-articular injection of PVA Hydrogel, novel polyvinyl alcohol preparation, as compared to hyalan G-F20, (Synvisc-One®) one of the most commonly used and best performing hyaluronic acid based products, in patients with symptomatic knee osteoarthitis (OA).
Detailed description
To compare the effects of a single intra-articular injection of a novel polyvinyl alcohol preparation (PVA Hydrogel) and hylan G-F20 (Synvisc-One®) in patients with symptomatic knee OA. Patients with knee OA (ACR clinical and radiological criteria) symptoms for ≥6 months, insufficient/failed response to analgesics, K&L stage II-III (x-Rays within past 12 months), a knee pain score of 4-9 (0-10 NRS) in the target knee and \<3 in the contralateral knee, will be enrolled in a randomised, controlled, double-blind, parallel group 26-week clinical investigation to receive a single intra-articular injection of PVA Hydrogel or Synvisc-One®. Safety (both at the injection site (primary end-point) and overall) and efficacy (change in pain in the target knee (0-10 NRS), WOMAC Osteoarthritis Index (total and subscales) and Patient's Global Assessment of knee OA (0-10 NRS)) will be evaluated. After signing an informed consent, patients will be screened at least 7 days before randomisation, when they will received a single intra-articular injection of either PVA Hydrogel or Synvisc-One® (1:1 allocation ratio) and will be then seen for follow-up 1, 2 and 4 days (this latter just in case of AE occurrence at the target knee) and 2, 4, 8, 12, 18 and 26 weeks after IA injection.
Interventions
DEVICEPVA Hydrogel
PVA Hydrogel will be supplied in 2 mL sterile and endotoxins-free pre-filled syringes containing a biocompatible polyvinyl alcohol crosslinked (PVA CL, main component) and buffered water for injections.
DEVICESynvisk-One®
Synvisc One® (comparator) will be supplied in a 6 mL sterile and non-pyrogenic syringe containing containing Hylan polymers (hylan A + hylan B) (main component), sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate monohydrate and water for injections.
Sponsors
Rottapharm Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Given the impossibility of obtaining identical presentations of the compared interventions, double-blind conditions will be ensured by appointing at each site one injector investigator in charge only of the administration of the treatments and one clinical assessor investigator as Outcome Assessor, in charge of all safety and efficacy assessments, who will remain always blinded to the treatment. Patient blinding will be ensured by avoiding visual access to the injection field by the use of a screen between the patient and his/her knee.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Signed and dated informed consent obtained before undergoing any clinical-investigation-related procedure. 2. Male or female aged between 40 and 80 years. 3. Documented diagnosis of primary OA of the knee, based on the clinical and radiological American College of Rheumatology (ACR) criteria for knee OA: * Knee pain, * X-ray osteophytes, * at least one of the following: (a) age \>50 years; (b) morning stiffness \<30 minutes in duration; (c) crepitus on active motion. 4. Grade II-III according to the Kellgren and Lawrence classification (X-ray evidence at enrolment or within the previous 12 months). 5. Knee OA symptoms for at least six months. 6. Failure to respond (i.e. did not respond sufficiently) to analgesics and/or regular NSAIDs, or proven intolerance to regular use of NSAIDs or to weak opioids analgesics. 7. Presence of pain in the target knee, with a value ≥4 and ≤9 on the NRS, providing that pain in the contralateral knee I less than 3 (see also
Exclusion criteria
n. 3). 8. Ability and willingness to communicate, participate, and comply with the requirements and scheduled procedures of the clinical investigation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events at the injection site (target knee) | 6 months | patient reported symptom and/or investigator detected clinical sign |
| Adverse Device Events | 6 months | AEs considered as related to the device and/or to the IA procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physical examination | 6 months | a complete physical examination will be carried out at all scheduled clinic visits and/or at any unscheduled/early termination visit in case of premature discontinuation. Clinically significant findings of the physical examination at screening will be documented as concomitant diseases. New findings or worsening of a finding at all visits following the screening visit will recorded as adverse events. |
| Blood pressure | 6 months | Systolic and diastolic blood pressure (mmHg) |
| Pulse rate | 6 months | Radial pulse rate (beats/minute) |
| Body temperature | 6 months | Body temperature will be assessed via a mouth thermometer (degrees Celsius (°C) |
| Device Deficiencies | 6 months | malfunctions, use errors and inadequate labelling occurred before, during or after the use of the devices |
| WOMAC Index | 6 months | tri-dimensional, disease-specific, self-administered, health status measure, to assess pain, stiffness and physical function in patients with knee OA, NRS format, version 3.1, 48 hours recall period |
| Patient's Global Assessment of knee OA | 6 months | overall judgment of efficacy (Considering all the ways your knee osteoarthritis affects you, how would you rate the severity of your condition over the last week? according to a 0-10 NRS scale, anchored at 0 = I am feeling very well and 10 = I am feeling as bad as possible |
| Rescue medication use | 6 months | Number of paracetamol tablets taken each day |
| Knee pain | 6 months | 0-10 NRS (0=no pain to 10=the worst possible pain) during past 48 hours |
| Adverse Events | 6 months | any AE irrespective of target knee involvement |
Countries
Poland
Outcome results
None listed