Euflexxa for the Treatment of Osteoarthritis

A Prospective Pilot Study to Evaluate Efficacy and Safety of Euflexxa for the Treatment of Osteoarthritis

The effect of Euflexxa therapy for knee osteoarthritis on levels of inflammatory and degenerative synovial fluid bio-markers in patients with knee osteoarthritis

Study Overview

• Status: Completed
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Device: Euflexxa

Detailed Description

The FLEXX trial was the first well-controlled, randomized, double-blind, multicenter study evaluating the efficacy of Euflexxa (1% sodium hyaluronate) therapy for knee osteoarthritis. Five-hundred-and-eighty patients were randomized to receive either Euflexxa or normal saline. There were significant improvements in the Visual analogue scale score Osteoarthritis Research Society International responder index, HRQoL, and function at 26-week follow-up.1 However, the FLEXX trial did not evaluate changes in synovial fluid bio-marker levels. The present study will be a prospective pilot study of 30 knees from subjects who receive intra-articular Euflexxa. The primary objective of this study is to prospectively determine, at 6-weeks, and 6-months post treatment, the changes in levels of synovial fluid biomarkers from pre- to post-injection in patients who receive Euflexxa. In addition, we will assess patient reported pain and patient reported outcomes up to 2 years from initiation of study.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. OA of the knee by American College of Rheumatology criteria
2. Those who failed non-pharmacological measures or simple analgesics
3. moderate to severe pain score of 41 to 90 mm recorded on 100-mm visual analog scale (VAS) immediately following a 50-foot walk
4. bilateral standing anterior-posterior radiograph demonstrating Kellgren and Lawrence grade 2 or 3 OA of the target knee
5. ability and willingness to use only acetaminophen as the analgesic (rescue) study medication
6. unassisted walking 50 feet on a flat surface and going up and down stairs
7. willingness and ability to complete efficacy and safety questionnaires

Exclusion criteria:

1. Age less than 18 years
2. any major injury to the target knee within the prior 12 months
3. any surgery to the target knee within the prior 12 months
4. surgery to the contralateral knee or other weight-bearing
5. inflammatory arthropathies
6. gout or pseudogout within the previous 6 months
7. radiographic acute fracture, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee
8. osteonecrosis of either knee
9. fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication
10. target knee joint infection or skin disorder/ infection within the previous 6 months
11. symptomatic OA of the hips, spine, or ankle; known hypersensitivity to acetaminophen, IA-BioHA, or phosphate-buffered saline solution
12. Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the study
13. history of immune disorders; vascular insufficiency of lower limbs or peripheral neuropathy
14. current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin)
15. active liver or renal disease
16. any clinically significant abnormal laboratory value [to be defined in detail at a later point]
17. any intercurrent chronic disease or condition that might interfere with the completion of the study
18. participation in any experimental device study within the prior 6 months or any experimental drug study within the prior month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Euflexxa; Two sets of Euflexxa injection at 0 and 6 months. Each set consists of 3 injections 1 week apart.	Device: Euflexxa; Aspirations performed before each injection and at six weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hyaluronate Concentration	The concentration of hyaluronate in the synovial fluid will be measured using Fluorophore-assisted carbohydrate electrophoresis. The difference between the mean concentration at baseline and 6 months is reported.	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)	The levels of TSG-6 in the synovial fluid will be measured using Enzyme-linked immunosorbent assay. The difference in mean concentration between baseline and 6 months post injection is reported.	Baseline to 6 months
VAS Pain Score Improvement	Change in VAS (visual analogue scale) pain score compared to baseline in the study cohort. VAS is a measure of pain with 0 being best and 10 being worst pain on a 10 cm scale (100 mm).	Baseline to 6 months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Carlos A Higuera, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2018
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): October 31, 2021

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: March 2, 2018
• First Posted (Actual): March 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 17-1668

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No