Different Volumes of Durolane in Knee OA

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the safety and efficacy profiles of new single-injection volumes of Durolane in patients with knee OA.

Detailed Description
-----------------
To assess the safety and efficacy profiles of different volumes of Durolane in patients with knee OA and compare with the current standard single-injection of the product. The study aims to investigate whether different volumes of Durolane compared to the standard injection volume will improve the benefit/risk profile.

Official Title
-----------------
Double-Blind, Randomized Study of Three Different Volumes of Durolane in Subjects With Osteoarthritis of the Knee

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Device: Durolane 3 ml, Durolane 4,5 ml, Durolane 6 ml


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject (female or male) 40-85 years of age Unilateral knee pain fulfilling American College of Rheumatology (ACR) criteria for diagnosis of osteoarthritis(OA) Radiographic evidence of OA in the study knee WOMAC pain score of 7-17 in the study knee WOMAC pain score of 2-3 in the study knee (WOMAC Likert 3.1 A1) Subject normally active Subject has attempted but not responded adequately to previous non-pharmacological therapy(ies)and to simple analgetics Subject cooperative and able to communicate effectively with the investigators Body mass index ≤ 35 kg/m2; Signed informed consent obtained Exclusion Criteria: Knee effusion Contralateral knee OA Clinically significant joint pain from joints other than the knee Previous intra-articular steroid injection into the study knee within the last 6 months Previous intra-articular Hyaluronic Acid (HA) injection into the study knee within the last 9 months Previous allergic type reaction to a HA product Treatment with analgesics other than paracetamol (acetaminophen) (including topical agents for the knee) within 5 half lives of the drug prior to the baseline visit Use of analgesics 48 hours preceding the baseline visit Use of systemic glucocorticosteroids (excluding inhaled steroids) within the last 3 months Treatment with glucosamine/chondroitin sulfate initiated within the past 3 months Change in physical therapy for the knee within the last three months Arthroscopy or other surgical procedure in the study knee within the past 12 months Serious injuries to the study knee in the past Any planned arthroscopy or other surgical procedure during the study period Previous history or presence of active septic arthritis Active skin disease or infection in the area of the injection site Systemic active inflammatory condition or infection Bleeding diathesis or use of anticoagulants History of drug or alcohol abuse within 6 months Any medical condition that in the opinion of the investigator makes the subject unsuitable for inclusion Pregnant or breastfeeding woman or woman of childbearing potential not practicing adequate contraception Involvement in other clinical trials

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durolane 3ml<br>Durolane 3 ml is an Intraarticular hyaluronic acid | Device: Durolane 3 ml, Durolane 4,5 ml, Durolane 6 ml<br>* Durolane is an intraarticular hyaluronic acid preparation<br>|
| Experimental: Durolane 4.5<br>Durolane 4.5 is an Intraarticular hyaluronic acid | Device: Durolane 3 ml, Durolane 4,5 ml, Durolane 6 ml<br>* Durolane is an intraarticular hyaluronic acid preparation<br>|
| Experimental: Durolane 6 ml<br>Durolane 6 ml is an Intraarticular hyaluronic acid | Device: Durolane 3 ml, Durolane 4,5 ml, Durolane 6 ml<br>* Durolane is an intraarticular hyaluronic acid preparation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pain Over 26 Weeks (Change From Baseline) | The study aims to compare the change of pain for different volumes of study product over 26 weeks using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score that consists of 5 questions. It is a 5-graded Likert scale: None, Mild, Moderate, Severe or Extreme relating to how much pain the subject has experienced during the last 48 hours. The score of each dimension is calculated by simply adding the score (from 0 to 4) for each question. | 26 weeks after treatment compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability From Baseline to 26 Weeks After Treatment. | Safety and tolerability will be assessed at each clinic visit (Baseline, 2, 6, 12, 18 and 26 weeks). Standard questions was used, Since your last clinical visit have you had any health problems?. | From baseline to 26 weeks after treatment | 
| WOMAC Stiffness Score (Change From Baseline) | The study aims to compare the change of stiffness for different volumes of study product over 26 weeks using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) stiffness score that consists of 2 questions. It is a 5-graded Likert scale: None, Mild, Moderate, Severe or Extreme relating to how much stiffness the subject has experienced in the last 48 hours. The score of each dimension is calculated by simply adding the score (from 0 to 4) for each question. | 26 weeks after treatment compared to baseline | 
| WOMAC Physical Function Score (Change From Baseline) | The study aims to compare the physical function for different volumes of study product over 26 weeks using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) physical function score that consists of 17 questions. It is a 5-graded Likert scale: None, Mild, Moderate, Severe or Extreme relating to performing daily physical activities the subject has experienced in the last 48 hours. The score of each dimension is calculated by simply adding the score (from 0 to 4) for each question. | 26 weeks after treatment compared to baseline | 
| Subject´s Global Assessment of the Status of the Study Knee (Change From Baseline) | The subject will assess his/her global status how the study knee affects them by using a 11-point numerical rating scale, Subject global assessment scale, from very poor=0 to excellent=10. | 26 weeks after treatment compared to baseline |