Intra-articular Administration of Med Device Made of Biological Vegetal Matrix for the Treatment of Knee Osteoarthritis

A Randomized, Parallel Group, Single Blind Clinical Trial Against Active Comparator to Evaluate the Efficacy and Safety of a Medical Device Made of a Vegetal Biological Matrix for the Treatment of Knee Osteoarthritis.

A pre-market randomized, parallel group, single-blind, clinical study with a Medical Device, made of vegetal material, to evaluate the efficacy and safety of one knee injection of the investigational device versus active comparator (Jonexa). The study population will consist of 150 patients diagnosed with primary knee osteoarthrosis. At present, the study is monocentric competitive.

Treatment period for each patient is 6 months.

Study Overview

• Status: Recruiting
• Conditions: the Treatment of Knee Osteoarthritis
• Intervention / Treatment: Device: Medical Device Iniettabile Ginocchio

Detailed Description

150 patients diagnosed with primary knee osteoarthritis will be enrolled by up to 3 centers.

The study includes 7 visits at the site center.

V-1 (eligibility assessment / screening visit):

• Collection of written informed consent
• Physical examination, including measurement of anthropometric parameters and vital signs (height, weight, diastolic / systolic pressure, heart rate)
• Diagnosed with radiologically confirmed primary osteoarthritis of the knee according to American College of Rheumatology criteria (i.e. one or more osteophytes and a measurable joint space on a plain radiograph taken within 3 months prior to screening).
• Blood tests: glycemia, creatinine, complete blood count with formula, ALT, AST, ALP, calcium, potassium, sodium, C reactive protein, total bilirubin. Urinalysis.
• Advice on daily diary writing to collect the number of concomitant medication before V0
• Recording of adverse events and concomitant therapies in the daily diary

V0 (confirmation of possession of selection criteria):

• Physical examination, including measurement of anthropometric parameters and vital signs (height, weight, diastolic / systolic pressure, heart rate)
• Randomization 1:1 to Investigational device or active comparator Jonexa
• Intra-articular administration
• Observation of the patient for 30 minutes post injection
• Compliance with daily diary completion
• Administration of questionnaires: WOMAC Pain and Function, SF-36 and global symptom relief questionnaire (CGI- I).
• Recording of any changes in concomitant therapies and any adverse events.

V1(Day 3): safety visit (3 days after V0)

• Objective examination, including measurement of vital parameters (weight, diastolic/systolic blood pressure, heart rate).
• Safety evaluation and AEs recording and Concomitant Therapies
• Checking the completion of the daily diary.

V2 (V2, week 2 ± 2 days) follow-up visit:

• Objective examination, including measurement of vital parameters (weight, diastolic/systolic blood pressure, heart rate).
• Checking the completion of the daily diary.
• Administration of the global symptom relief questionnaire (CGI- I).
• Administration of the WOMAC Pain questionnaire.
• Recording of adverse events and concomitant therapies.
• Instruction to fill in the daily diary via web app (smart phone) to report the use of all concomitant therapies. If patient is not able to use web app, a paper copy will be given.

V3 (V3, week 4 ± 2 days): follow-up visit:

• Objective examination, including measurement of vital parameters (weight, diastolic/systolic blood pressure, heart rate).
• Checking the completion of the daily diary.
• Administration of the global symptom relief questionnaire (CGI- I).
• Questionnaire administration: WOMAC Pain and Function, SF-36.
• Recording of adverse events and concomitant therapies.
• Instruction to fill in the daily diary via web app (smart phone) to report the use of all concomitant therapies. If patient is not able to use web app, a paper copy will be given.

V4 (V4, week 12 ± 2 days) follow-up visit:

• Physical examination, including measurement of anthropometric parameters and vital signs (height, weight, diastolic / systolic pressure, heart rate)
• Check of daily diary
• Administration of the global symptom relief questionnaire (CGI- I).
• Questionnaire administration: WOMAC Pain and Function, SF-36.
• Recording of adverse events and concomitant therapies.
• Instruction to fill in the daily diary via web app (smart phone) to report the use of all concomitant therapies. If patient is not able to use web app, a paper copy will be given.

V5 (V5, week 24 ± 3 days) end-of-study or premature discontinuation visit:

• Objective examination, including measurement of vital parameters
• Blood tests: blood glucose, creatinine, blood count with formula,AST, ALP, calcemia, potassium, sodium, C-reactive protein, total bilirubin. Urine examination.
• Check of completion of the daily diary.
• Administration of the global symptom relief questionnaire (CGI- I).
• Questionnaire administration: WOMAC Pain and Function, SF-36.
• Recording of adverse events and concomitant therapies.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caterina Fossi, PHD; Phone Number: +39 3351894461; Email: cfossi@aboca.it
• Study Contact Backup: Name: Laura Capone, PHD; Phone Number: +39 0575 745568; Email: lcapone@aboca.it

Study Locations

• Italy
  • Perugia, Italy, 06156
    • Recruiting
    • Azienda Ospedaliera di Perugia
    • Contact: Francesco Manfreda, MD; Email: francesco.manfreda@libero.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed Informed Consent
2. Patient of both sexes over 40 years of age
3. Diagnosis of primary osteoarthritis of the knee according to the criteria of the American College, radiologically confirmed, i.e., one or more osteophytes and a measurable joint space on a standard radiograph taken within 3 months prior to screening.
4. Score ≥2 in the target knee on a Likert scale at WOMAC pain question 1 (i.e. pain while walking on a flat surface) at the V-1 screening visit (to be confirmed at the V0 baseline visit). The target knee is defined as the knee with osteoarthritis in the case of unilateral pathology or the only one with this criterion in the case of bilateral pathology.
5. Severity grade of arthrosis 2 or 3 according to Kellgren & Lawrence classification.
6. Be willing to maintain stable eating habits and lifestyle throughout the study period

Exclusion Criteria:

1. Intake of analgesics, NSAIDs or opioids within 5 days prior to the start of the run-in (i.e. prior to V-1).
2. Body Mass Index (BMI) ≥ 30 kg/m2 .
3. Pregnant women.
4. Intra-articular visco supplementation in the target knee in the preceding 9 months.
5. Cycle of treatment with systemic corticosteroids or intra-articular corticosteroid injection in any joint in the 3 months prior to screening.
6. Symptomatic arthrosis of the contralateral knee with a score ≥3 on a Likert scale to WOMAC pain question 1 (pain while walking on a flat surface) at V-1 (to be confirmed at V0), or severe symptomatic hip arthrosis.
7. Significant deformity: genu varum, ligament laxity or meniscus instability.
8. Presence of autoimmune diseases (excluding chronic autoimmune thyroiditis) or other chronic inflammatory processes (e.g. rheumatoid arthritis, ongoing infections, gout).
9. Ongoing infections.
10. Established or presumed allergy to hyaluronic acid, echinacea or centella.
11. Patients with malignant neoplasms of any kind, or with a history of malignant neoplasms except for patients with a positive history of a malignant neoplasm that has been surgically removed and has not recurred within five years prior to study participation.
12. Abuse of alcohol, narcotics or psychotropic drugs that can alter the state of vigilance and physical perception.
13. Dementia of any kind or other possible causes of progressive deterioration of the mental soundness, or any psychological or physical disability that reduces the ability to take the treatment under study as intended.
14. Inadequate reliability or presence of conditions that may lead to non- compliance/adherence of the patient to the protocol.
15. Previous participation in a clinical study within the last 30 days.

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: Experimental Arm; Arm: Medical Device Iniettabile Ginocchio	Device: Medical Device Iniettabile Ginocchio; Knee injection of the investigational device( MD Iniettabile Ginocchio) versus active comparator (Jonexa).
Active Comparator: Comparator Arm; Arm: Medical Device Jonexa (active comparator medical device from the market )	Device: Medical Device Iniettabile Ginocchio; Knee injection of the investigational device( MD Iniettabile Ginocchio) versus active comparator (Jonexa).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change at 2 weeks from baseline in WOMAC Pain	To the patient will be asked to answer 5 questions about the pain experienced in the previous 48 hours, during different activities, using a 5-point Likert scale (0 to 4) for each answer. The total score (minimum 0; maximum 20) is given by the sum of the 5 answers given.	[Time Frame: 14 days]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in WOMAC function	To the patient will be asked to answer 16 questions about the function in the previous 48 hours, during different activities, using a 5-point Likert scale (0 to 4) for each answer. The total score	Time Frame: 14 days
Change in WOMAC pain and function at 4, 12, 24 weeks from baseline	To the patient will be asked to answer " WOMAC pain and function" questions about the function in the previous 48 hours, during different activities, using a 5-point Likert scale at 4, 12, 24 weeks from baseline	Time Frame: baseline, 4, 12, 24 weeks
Change in SF-36 at 4, 12, 24 weeks from baseline	To the patient will be asked to answer " Change in SF-36 "at 4, 12, 24 weeks from baseline	Time Frame: baseline, 4, 12, 24 weeks
Adequate global relief of symptoms after treatment	Adequate global relief of symptoms after treatment, defined by a score of at least 3 on a 7-point Likert scale of weekly relief (Clinical Global Impression - Improvement, (CGI-I) scale): In order to assess adequate global relief, patients will be asked at each post-basal visit (from visit V2 onwards) to answer the question "Compared to how you usually felt before taking the study treatment, how would you rate your global symptom relief over the last 7 days?" Possible answers: 1, much improved; 2, improved; 3, slightly improved; 4, unchanged; 5, slightly worsened; 6, worsened; 7, much worsened.	Time Frame: 2, 4, 12, 24 weeks

Collaborators and Investigators

• Sponsor: Bios-Therapy, Physiological Systems for Health S.p.A
• Collaborators: Iqvia Pty Ltd
• Investigators: Principal Investigator: Auro Caraffa, MD, Azienda Ospedaliera di Perugia

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

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: NBM-KOA 05/21

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