Treatment of Knee Osteoarthritis With PAAG-OA

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind clinical investigation to compare the effectiveness of intra-articular polyacrylamide hydrogel (PAAG-OA) and a hyaluronic acid, Synvisc-One to induce symptomatic benefit in subjects with knee osteoarthritis.

Official Title
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A Multi-centre Randomized, Controlled, Double-blind Clinical Investigation of Intra-articular Polyacrylamide Hydrogel in Subjects With Knee Osteoarthritis Followed by an Open Label Extension Study

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Device: PAAG-OA
* Device: Synvisc-One


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged ≥ 40 years Clinical diagnosis of knee OA American College of Rheumatology criteria confirmed by radiology Definite radiographic OA in the most symptomatic knee (target knee) at mild to moderate-stage (Kellgren-Lawrence grades 2 or 3) Stable dose of analgesics for the past four weeks NRS (11 points (0-10) pain intensity numerical rating scale) ≥ 4 in target knee, during the past week when walking Body Mass Index (BMI) between 20-35 For females of reproductive potential: use of adequate contraception must be used throughout the trial Exclusion Criteria: Female participants who are pregnant, lactating or planning pregnancy during the course of the clinical investigation Contraindications to PAAG-OA or Synvisc-One®, according to IB or Instruction for Use (IFU) Previous intra-articular injection of polyacrylamide gel in the target knee Previous intra-articular injection with hyaluronic acid or derivatives in target knee in the previous 6 months Significant valgus/varus deformity of the knee, ligamentous laxity or meniscal instability Other diseases in target knee than osteoarthritis Intra-articular injection of any substance other than hyaluronic acid (e.g. corticosteroids) in the target knee within the last 3 months Acute serious infection of any region that required hospital care or intravenous antibiotic treatment within the last 30 days, or oral antibiotic treatment within the last 14 days Skin disease or infections in the area of the injection site Infected or severely inflamed knees History of sepsis in any joint or any clinical concern for a subacute infectious process in the target knee History of surgery in the target knee within the past 6 months Symptomatic osteoarthritis of the hips, spine or ankle, that interferes with the evaluation of the target knee Planned surgery on any lower extremity Clinically significant venous or lymphatic stasis present in the legs Clinically apparent tense effusion or inflammation in the target knee Suffering from any unstable or severe cardio-vascular disease Any contraindication to intra-articular e.g. anticoagulant therapy or clinical concern for potential coagulopathy (e.g. liver disease) Any foreign material in the target joint Any significant medical condition (e.g. significant psychiatric or neurological disorders or active alcohol/drug abuse), any medical condition that is unstable/poorly controlled or other factors that may interfere with study participation Treatment with systemic steroids History of drug/alcohol abuse, mental dysfunction of other factors limiting their ability to cooperate fully Change in physiotherapy within the previous month Fibromyalgia Inflammatory or other disease/condition which may affect joints (e.g. rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis among others) Haemophilia Any other condition that in the opinion of the investigator put a potential participant at risk or otherwise precludes participation in the trial Known allergic reactions to components of Synvisc-One (avian protein) Known allergic reactions to antibiotics (azithromycin and moxifloxacin) or local anaesthesia Participation in any experimental device study within 6 months prior to enrolment, or participation in an experimental drug study within 1 month prior to enrolment

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PAAG-OA<br>Intra-articular injection with PAAG-OA (polyacrylamide hydrogel) | Device: PAAG-OA<br>* Intra-articular injection of 6ml PAAG-OA in the target knee (incl. five (5) years follow-up) period.<br>|
| Active Comparator: Synvisc-One<br>Intra-articular injection with Synvisc-One (hyaluronic acid) | Device: Synvisc-One<br>* Intra-articular injection of 6ml Synvisc-One in the target knee<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing one injection of PAAG-OA with one injection of Synvisc-One on pain over 6 months in subjects with knee osteoarthritis | Change in WOMAC (WOMAC Osteoarthritis Index) pain subscale. Pain is reported in each of five response categories (0=none, 4=extreme) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC | WOMAC (WOMAC Osteoarthritis Index) self reported pain, stiffness and physical function, categories (0=none, 4=extreme) | 1, 3, 6 and 12 months | 
| PGA (Patient Global Assessment) | PGA reported on a 10 cm Visual Analogue Scale | 1, 3, 6 and 12 months | 
| EQ-5D-5L, QoL | EQ-5D-5L, Quality of Life, comprised of descriptive system where each dimension has 5 levels (ranging from no problems to extreme problems) and a 20 cm Visual Analogue Scale (0 = worst health and 100 = best health) | 1, 3, 6 and 12 months | 
| OMERACT-OARSI responder criteria | Per the OMERACT-OARSI criteria, a subject is classified as a positive responder if at least one (1) of the following two (2) conditions is observed at the post-baseline assessment: In either pain (WOMAC pain subscale) or function (WOMAC function subscale), a high improvement in the subscale, where high improvement in a subscale is achieved if there is both a > 50% improvement from Baseline and an absolute change from Baseline of > 20 normalised units (0-100 scale) OR Improvement in at least two (2) of the following three (3): Improvement in pain (WOMAC pain subscale) defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 (0-100 scale) Improvement in function (WOMAC function subscale) defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 (0-100 scale) Improvement in PGA defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 mm (0-100 sc | 1, 3, 6 and 12 months |