Treatment of Knee Osteoarthritis With PAAG-OA (ROSA)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Device: Synvisc-One; Device: PAAG-OA

Detailed Description

The trial is designed as a multi-center, randomised, controlled, double-blind, and parallel-group trial spanning over 12 months with outcome assessments at baseline, 1, 3, 6 and 12 months incl. follow-up period between 2-5 years. Primary endpoint at 6 months. The trial is designed to compare effectiveness and safety of injection of PAAG-OA and Synvisc-One® in participants with knee OA.

• Study Type: Interventional
• Enrollment (Estimated): 238
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark
    • The Parker Institute
  • Hillerød, Denmark
    • A2 Reumatologi og idrætsmedicin
  • Odense, Denmark
    • Reumatolog i Odense

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Contura
• Investigators: Principal Investigator: Henning Bliddal, MD, The Parker Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): October 1, 2020
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Protective Agents; Viscosupplements; Hylan
• Other Study ID Numbers: CON-OA-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No