Knee OsteoArthritis Long-term Assessment (KOALA)

Randomized Controlled Single-Blind Multi-Centre Evaluation of the Safety and Performance of an Injection of Hydrogel OA 2% in Subjects With Knee Osteoarthritis

The goal of this clinical study is to learn if Hydrogel OA 2% injection is safe and whether it works to improve symptoms of diagnosed knee osteoarthritis in adults when compared to Hyaluronic Acid (Durolane), a treatment that is currently often used for treatment of knee osteoarthritis. The main question it aims to answer is:

- How many study participants will experience side effects related to Hydrogel OA 2% during the study when compared to Hyaluronic Acid (Durolane)?

All study participants will receive either one Hydrogel OA 2% or Hyaluronic Acid (Durolane) injection in their knee during the clinical study. Study participants will not know which treatment they have received. Study participants will also receive a call from the researchers and visit the clinic three times to report whether they have experienced any side effects, and complete a questionnaire that will ask questions on whether their symptoms have improved since they received an injection.

Study Overview

• Status: Withdrawn
• Conditions: Knee Osteoarthritis (Knee OA)
• Intervention / Treatment: Device: Hydrogel OA 2%; Device: Hyaluronic Acid (Durolane)

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • More Institute
  • Bruges, Belgium
    • Az Sint Jan Brugge
  • Edegem, Belgium
    • UZ Antwerpen
  • Liège, Belgium
    • Chu Liege
  • Roeselare, Belgium
    • AZ Delta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults accepting to participate in the study and having signed the written informed consent form before any protocol-specific procedures and able to understand and follow the instructions as described in the protocol.
• Unilateral symptomatic tibiofemoral KOA confirmed by a "standing knee" X-ray. In case of bilateral KOA on X-ray only one knee (indexed knee) presents symptomatic OA pain.
• Age 35 ≤ 75 years.
• BMI 20 ≤ 35.
• Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain score 25-85.
• Radiological Kellgren and Lawrence (K&L) grade II and III from a standing knee radiograph with minimum joint space of 1 mm in the study knee.
• Fully ambulatory for functional assessments.
• Willingness to refrain from taking any pain medication for 48 hours prior to each study visit.
• Female subjects must be on effective contraception (pill, patch, ring, diaphragm, implant or intrauterine device), if not surgically sterile (tubal ligation or hysterectomy) or postmenopausal for at least one year. Females must show a negative pregnancy test at the treatment visit.

Exclusion Criteria:

• Bilateral tibiofemoral KOA where the non-symptomatic knee presents worse radiological grade of KOA.
• Radiological K&L grade 0, I, or IV from a standing knee radiograph assessed during the screening visit, using the most recent x-ray taken either immediately or within the past 3 months. Significant clinically assessed varus or valgus deformation of the selected knee side of more than 10 degrees.
• Extension deficit of the index knee of higher than 5 degrees.
• Bilateral symptomatic tibiofemoral KOA or a combined unilateral symptomatic tibiofemoral knee and hip OA.
• Clinical signs of significant effusion with noticeable swelling and/or inflammation related severe pain during the treatment visit.
• Evidence of active lymphatic or venous stasis or serious blood disorders (e.g., anemia), bleeding disorders (e.g., hemophilia), blood clots, or blood cancers (e.g., leukemia, lymphoma, and myeloma).
• Active bacterial infection, resulting in hospitalization and/or requiring intravenous antibiotic treatment.
• Synovial infection, skin infections or any skin diseases in the area of the injection site.
• History of autoimmune diseases that cause chronic joint pain and inflammation in the knee joint, including rheumatoid arthritis, psoriasis arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, gout, pseudogout, systemic sclerosis, Sjögren's disease, adult-onset still's disease.
• Known or suspected generalized chronic pain disorder.
• Severe alteration of mobility preventing any functional assessment.
• Allergy or hypersensitivity to any of the product components.
• Conditions (orthopedic, rheumatologic, musculoskeletal or inflammatory) causing symptomatic and/or radiating pain in the lower extremities that might interfere with the symptomatic OA knee pain, including hip OA assessed by physical examination by the physician.
• Symptomatic patellofemoral knee OA.
• Oral corticotherapy ≥4 mg/day (in prednisone equivalent) in the last 3 months before injection.
• Severe acute illness within 14 days prior to investigational device administration.

Any intra-articular injection (hyaluronan, hydrogel, soft implant, corticosteroid, platelet-rich plasma, local anesthetic etc.) arthroscopy, surgery in the treated knee; or cell-based therapy or an invasive procedure on the treated knee in the last 6 months before screening visit.

• Anticipated need for any surgical or other invasive procedure throughout the course of the clinical investigation, including prosthesis in the treatment knee, any concurrent OA treatments including alternative treatments (e.g., acupuncture, ultrasound, magnetic resonance etc.).
• Any investigator-assessed clinically significant condition that may represent a substantial risk to the patient or may have an impact on the study assessments.
• Participation in another clinical trial in the last 3 months before injection.
• Pregnancy and breastfeeding.
• Legal incapacity or limited legal capacity to consent.
• Trauma of the treatment knee in the last 6 months before the treatment visit.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrogel OA 2%; treatment arm	Device: Hydrogel OA 2%; Hydrogel OA 2% is a sterile, nonpyrogenic viscoelastic hydrogel suspension, designed using highly purified biopolymers in a phosphate-buffered saline solution. The main component is a cross-linked protein (ultra-pure bovine gelatin). The other main component is a polysaccharide cellulose nanocrystal (CNC) that acts as the crosslinker. Hydrogel OA 2% is supplied in pre-filled 2.25ml Luer lock syringe. Each package contains one syringe containing 2.0 mL Hydrogel OA 2%. Hydrogel OA 2% is designed to provide symptomatic relief by restoring joint lubrication and cushioning, potentially leading to reduced pain and improved joint function. The device is suitable for use in early and moderate OA (Kellgren and Lawrence, K&L, II-III).
Active Comparator: Hyaluronic Acid (Durolane); control arm	Device: Hyaluronic Acid (Durolane); DUROLANE contains 20 mg/mL of stabilized non-animal hyaluronic acid in buffered physiological sodium chloride solution pH 7. DUROLANE is a sterile, transparent viscoelastic gel supplied in a 3 mL glass syringe.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Hydrogel OA 2% in subjects with symptomatic KOA	The primary aim of this study is to test the safety of Hydrogel OA 2% in patients with symptomatic KOA. Specifically, the aim is to demonstrate that the proportion of patients experiencing Hydrogel OA 2%-related AEs is equal to the the proportion of patients experiencing Durolane-related AEs .	From the treatment to the end of the follow up at 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) 'Pain' score at 26 weeks after treatment	The aim is to show that the change in Knee Injury and Osteoarthritis Outcome Score (KOOS) 'Pain' score in the treatment group is at least equal to the control group at 26 weeks after treatment	From the treatment to the end of the follow up at 26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
An improvement in Knee Injury and Osteoarthritis Outcome Score (KOOS) scores at 26 weeks after treatment, compared to baseline.	An improvement in KOOS 'Symptoms' score compared to baseline.; An improvement in KOOS 'Stiffness' score compared to baseline.; An improvement in KOOS 'Function, Daily Living' score compared to baseline.; An improvement in KOOS 'Function, Sports and Recreational Activities' score compared to baseline.; An improvement in KOOS 'Quality of Life' score compared to baseline.; Change in overall KOOS score compared to baseline.	From the treatment to the end of the follow up at 26 weeks

Collaborators and Investigators

• Sponsor: Allegro NV/SA
• Collaborators: QbD Clinical

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 17, 2025
• First Posted (Actual): February 21, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Knee Osteoarthritis; Hyaluronic acid; Knee Injury and Osteoarthritis Outcome Score (KOOS); Hydrogel OA 2%
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Wounds and Injuries; Arthritis; Joint Diseases; Rheumatic Diseases; Leg Injuries; Osteoarthritis; Osteoarthritis, Knee; Knee Injuries; Immunologic Factors; Physiological Effects of Drugs; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: DHF-001-DVaP-001-03

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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