Intra-articular Polyacrylamide Hydrogel in Gonarthrosis

An Open-label Multicenter Postmarketing Extension Study of Efficacy and Safety of Intra-articular HBISA Endoprosthesis of Synovial Fluid NOLTREX™ in Knee Osteoarthritis

The OLE was aimed to assess long-term safety and efficacy of one and two courses of IA HBISA in patients with knee osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Device: Hydrous biopolymer with silver ions "Argiform" (HBISA) endoprosthesis of synovial fluid NOLTREX™

Detailed Description

HBISA (polyacrylamide hydrogel) endoprosthesis of synovial fluid NOLTREX™ is intended for the symptomatic treatment of adult patients with osteoarthritis (OA) reducing pain and improving mobility.

The aim of the 6-month OLE was to evaluate the long-term safety and efficacy of one and two courses of IA Polyacrylamide hydrogel with silver ions in patients with knee osteoarthritis who had received at least one IA injection of NOLTREX™ and completed the visit 5 in the IA/PAAG-SI/OA/2019 study.

In OLE patients who had received a course of treatment (one or two weekly intra-articular injections of 4.0 NOLTREX™ depending on the stage of OA and the clinical response to treatment) in the parent study might receive a single repeat course of NOLTREX™ at the visits 1/2 or 3/4 when clinically indicated. The WOMAC was the primary outcome measure.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Non-budgetary healthcare facility "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
  • Omsk, Russian Federation
    • "Clinical Diagnostic Center "Ultramed", LLC
  • Saint Petersburg, Russian Federation
    • Private Healthcare Facilty "Clinical hospital "RZHD-Medicina" of the city Saint-Petersburg
  • Yaroslavl, Russian Federation
    • State budgetary healthcare facility of Yaroslavl Region "Clinical hospital №3"

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women over 50 years of age;
• Provision of signed informed consent form;
• Patients met ACR classification criteria for knee osteoarthritis (pain in the knee and at least three of the following: age >50 years, stiffness <30 min, crepitus, bony tenderness, bony enlargement and no palpable warmth);
• OA grades 2 and 3 on the Kellgren-Lawrence scale with the predominant involvement of the medial tibiofemoral region of the knee joint;
• Patients from the NOLTREX™ group of the parent study (IA/PAAG-SI/OA/2019) who completed all (5) study visits

Exclusion Criteria:

1. Pregnancy and breastfeeding;
2. History of trauma or surgery on the target knee joint;
3. Instability of the target knee joint;
4. Microcrystalline arthropathies (according to the history and taking into account clinical manifestations);
5. History of systemic inflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.);
6. Seronegative spondyloarthritis and reactive arthritis;
7. Increased rheumatoid factor;
8. Increased uric acid > 360 µmol/l;

9. Intra-articular injection into the target knee joint:

   • hyaluronates - within 12 months prior to patient enrollment in the study;
   • other synovial fluid endoprostheses (except for NOLTREX™ in the IA/PAAG- SI/OA/2019 study) within 24 months;
   • glucocorticoids - within 1 month before enrollment in the study;
   • NSAIDs - intra-articular injection at any time in the history.
10. Systemic pain medications (NSAIDs, opioid analgesics) within 1 week prior to Visit 0;
11. Effusion in the target joint;
12. The presence of inflammation or infection in the target joint, synovitis;
13. The need for continuous use of glucocorticoids in any dosage form;
14. Use of paracetamol within 48 hours prior to Visit 0;
15. A positive blood test result for one or more of the following infections: HIV, hepatitis B and C, syphilis;
16. Severe liver disease, defined as an increase in one of the following: ALT, AST, alkaline phosphatase, total bilirubin, GGT more than 3 times the upper limit of normal;
17. Kidney disease with a glomerular filtration rate as assessed by the Cockcraft-Gault formula less than 60 mL/min/1.73 m2 (stages III-V chronic kidney disease [CKD]);
18. Clinical manifest coxarthrosis;
19. Severe decompensated chronic or acute diseases and other conditions or other causes that, in the investigator's opinion, may prevent the patient from participating in the study or affect the study results ;
20. Participation in any other clinical trial except that IA/PAAG-SI/OA/2019 within 90 days prior to enrollment in the OLE.

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

Other: Medical Device: HBISA (polyacrylamide hydrogel) synovial fluid endoprosthesis NOLTREX™; Sixty-five (65) patients were included in the study and divided into three groups based on the number of NOLTREX™ courses received: Group A consisted of 5 patients who received 2 NOLTREX™ courses, the first course in the IA/PAAG-SI/OA/2019 study and the second one at Visits 1/2 of OLE (IA/PAAG-SI/OA/2020) study.; Group B comprised 43 patients who received 2 NOLTREX™ courses, the first course in the IA/PAAG-SI/OA/2019 study and the second one at Visits 3/4 of OLE.; Group C consisted of 17 patients who had received only 1 NOLTREX™ course in the parent study.

Device: Hydrous biopolymer with silver ions "Argiform" (HBISA) endoprosthesis of synovial fluid NOLTREX™; If clinically indicated patients received a repeat course of NOLTREX™ (one or two weekly intra-articular injections of 4.0 NOLTREX™ at the investigator's discretion depending on the stage of OA and clinical response to treatment).; Other Names: Polyacrylamide hydrogel with silver ions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Total WOMAC Score (WOMAC-T)	Mean change in WOMAC-T from baseline (visit 0 [screening] of OLE and visit 1 (week 1) of the parent study) to visit 3 (week 11) and visit 5 (week 23). Patients were asked to complete the questionnaire during the study visits. The Western Ontario and McMaster Universities Osteoarthritis Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100-mm VAS and consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The scores for each subscale are summed up, with a possible score range of 0-500 for Pain, 0-200 for Stiffness, and 0-1700 for Physical Function. Higher scores represent worse pain, stiffness, and functional limitations. A sum of the scores for all three subscales gives a total WOMAC score (0-2400), where 0 represents the best and 2400 the worst possible health status. The higher the score, the poorer the function. Therefore, an improvement was achieved by reducing the overall score.	baseline (OLE visit 0 and visit 1 study 1 [week 1]), OLE visits 3 (week 11) and 5 (week 23)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the WOMAC Pain Score (WOMAC-A)	Mean change in WOMAC-A from baseline (visit 1 (week 1) of the parent study AND visit 0 [screening] of OLE) to visit 3 (week 11) and visit 5 (week 23). Patients were asked to complete the questionnaire during the study visits. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a set of standardized questionnaires used by health professionals to evaluate pain, stiffness and physical functioning of the joints in patients with knee and/or hip osteoarthritis. The WOMAC Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS. The WOMAC pain scale consists of five items: (1) walking on flat ground; (2) going up or down stairs; (3) at night while in bed; (4) sitting or lying; and (5) standing upright. The scores for the Pain subscale are summed up, with a possible score range of 0-500. Higher scores represent worse pain.	baseline (OLE visit 0 and visit 1 study 1 [week 1]), OLE visits 3 (week 11) and 5 (week 23)
Change in the WOMAC Stiffness (WOMAC-B) Score	Mean change in WOMAC-B from baseline (visit 0 [screening] of the OLE and visit 1 [week 1] of the parent study) to visits 3 (week 11) and 5 (week 23). Patients were asked to complete the questionnaire during the study visits. The Western Ontario and McMaster Universities Osteoarthritis Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS and consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The scores for each subscale are summed up, with a possible score range of 0-200 for Stiffness, and 0-1700 for Physical Function. Higher scores represent worse stiffness and functional limitations. The higher the score, the poorer the function. Therefore, an improvement was achieved by reducing the overall score.	baseline (OLE visit 0 and parent study visit 1 [week 1]), visits 3 (week 11) and 5 (week 23)
Change in the WOMAC Physical Function (WOMAC-C) Score	Mean change in WOMAC-C from baseline (visit 0 [screening] of the OLE and visit 1 [week 1] of the parent study) to visits 3 (week 11) and 5 (week 23). Patients were asked to complete the questionnaire during the study visits. The Western Ontario and McMaster Universities Osteoarthritis Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS and consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The scores for each subscale are summed up, with a possible score range of 0-200 for Stiffness, and 0-1700 for Physical Function. Higher scores represent worse stiffness and functional limitations. The higher the score, the poorer the function. Therefore, an improvement was achieved by reducing the overall score.	baseline (OLE visit 0 and parent study visit 1 [week 1]), visits 3 (week 11) and 5 (week 23)
Change in the 100-mm VAS Pain Score Visual Analogue Scale (100 mm VAS)	Mean change in the VAS pain score from baseline (visit 0 [screening] of the OLE and visit 1 [week 1] of the parent study to visit 2 (week 1), visit 3 (week 11) and visit 5 (week 23). The 0 to 100 mm visual analogue scale (VAS) was used for measuring pain intensity. VAS ratings between 0 and 4 mm were interpreted as no pain, 5 to 44 mm, mild pain; 45 to 74 mm, moderate pain; and 75 to 100 mm, severe pain. The pain VAS was self-completed by the patients.	baseline (OLE visit 0 and study 1 visit 1 [week 1]), OLE visits 3 (week 11) and 5 (week 23)
Patient's Assessment of the Treatment Efficacy	Patient satisfaction with treatment was measured by a 6-point Likert scale (evident aggravation, aggravation, without changes, weak improvement, improvement, significant improvement) at the study visits 3 (week 11) and 5 (week 23).	visits 3 (week 13) and 5 (week 25)
Investigator's Assessment of the Treatment Efficacy	Investigator satisfaction with treatment was measured by a 6-point Likert scale (evident aggravation, aggravation, without changes, weak improvement, improvement, significant improvement) at the study visits 3 (week 11) and 5 (week 23).	visits 3 (week 13) and 5 (week 25)
Total Number of Paracetamol Tablets Taken	A patient diary was used to capture data about the number of paracetamol 500 mg tablets taken.	visits 3 (week 13) and 5 (week 25)
Total Number of NSAID Tablets Taken	A patient diary was used to capture data about the number of NSAID tablets taken. In case of paracetamol ineffectiveness and pain persistence patient was allowed to take protocol-permitted NSAID at certain doses.	visits 3 (week 11) and 5 (week 23)
The JSN in the Target Knee	Joint space narrowing (JSN) was scored by comparison of subsequent radiographs taken over time. An increase in the radiographic knee JSN is associated with osteoarthritis progression.	baseline (visit 1 of the parent study IA/PAAG-SI/OA/2019), visit 5 (week 23) of OLE

Collaborators and Investigators

• Sponsor: Research Centre BIOFORM
• Investigators: Principal Investigator: Vladimir V Popov, DSc, Non-budgetary HCF "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2020
• Primary Completion (Actual): December 28, 2020
• Study Completion (Actual): May 12, 2021

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: intra-articular; polyacrylamide hydrogel; PAAG; NOLTREX; HBISA (Hydrous biopolymer with silver ions "Argiform")
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis
• Other Study ID Numbers: IA/PAAG-SI/OA/2020

Drug and device information, study documents

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