Evaluation of the Effect of the CR500 SINGLE-DOSE GEL Medical Device in Patients With Knee Osteoarthritis (KOA)

Study Overview
=================
Brief Summary
-----------------
Single arm clinical investigation, post-market confirmatory interventional to assess performance, safety and tolerability of CR500 SINGLE-DOSE GEL medical device in patients with knee osteoarthritis (KOA).

Detailed Description
-----------------
Subjects 26-83 years old will receive CR500 SINGLE-DOSE GEL given for the treatment of osteoarthritis of the knee over a 4-week time period. The primary objective of the study is to evaluate the effect of CR500 SINGLE-DOSE GEL in the treatment of KOA.

Official Title
-----------------
Evaluation of the Effect of the CR500 SINGLE-DOSE GEL Medical Device in Patients With Knee Osteoarthritis (KOA): a Post-market Confirmatory Interventional, Single Arm Clinical Investigation

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Device: CR 500™ SINGLE-DOSE GEL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Male or Female, aged ≥18 years at the time of the signature of ICF (Informed Consent Form). Patients with a diagnosis of primary or secondary KOA affecting only one knee (monolateral KOA) of mild (score 1 - 4) or moderate (score 5 - 7) severity according to the LKI score. Willing to follow all study procedures, including attending all site visits, tests and examinations. Willing to participate in the study and sign the ICF. Exclusion criteria Osteoarthritis (OA) in both knees (bilateral KOA). Other - different - clinical conditions of the knee. Infective or inflammatory processes near the area of treatment. Damaged skin in the area of treatment. Ongoing cutaneous allergies. Serious and chronical pathological skin conditions (i.e. rosacea, psoriasis, vitiligo) including diagnosticated cancer with/without ongoing antitumor therapy. Allergy to device components (Sodium hyaluronate; Synthetic Human (SH)-Polypeptide-85; SH-Polypeptide-93; Glycerin; Propylene glycol; Ethylhexylglycerin; Panthenol; Polyethylene Glycol (PEG)-40 hydrogenated castor oil; Sodium hydroxide; Xanthan gum; Phenoxyethanol; Benzoic Acid; Carbomer; Dehydroacetic Acid; Disodium EDTA). Any other systemic or local therapy for the treatment of KOA. Any other systemic or local therapy (e.g. NSAIDs, corticosteroids) for the treatment of other inflammatory diseases (e.g. dermatitis, acute or chronic bronchitis, gastroenteritis, etc.) or painful states (e.g. headache, dental abscess, etc.) that may interfere with the clinical course of KOA under treatment with the medical device CR500. Immune system illnesses. Uncontrolled systemic diseases. Known drug and/or alcohol abuse. Mental incapacity that precludes adequate understanding or cooperation. Participation in another investigational study. Pregnancy* or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CR500 single-dose gel<br>Interventional study on CR500 1.5 mL will be topically administered twice a week for four weeks | Device: CR 500™ SINGLE-DOSE GEL<br>* CR 500™ SINGLE-DOSE GEL is a hydrogel to be applied to intact skin, useful to attenuate the physiological degeneration of cartilage typical of osteoarthritic processes. The presence of sodium hyaluronate facilitates the movement of joints and tendons for greater mobility and flexibility<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OA evaluation, measured by Lequesne Knee Index (LKI) | The primary efficacy endpoint of the study will be the evaluation of the clinical performance of the CR 500™, used as intended in patients affected by KOA, in variation of symptoms related to the physiological degeneration of cartilage typical of osteoarthritic processes, in terms of difference in LKI score between the end study visit and baseline visit. Lequesne Knee Index Score: minimum index score: 0 maximum index score: 24 0 means none OA >= means extremely severe OA | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lequesne Knee Index (LKI) Score | To evaluate the clinical performance of the CR 500™ across the study by Lequesne Knee Index (LKI) score. Lequesne Knee Index Score: minimum index score: 0 maximum index score: 24 0 means none OA >= means extremely severe OA | 4 weeks | 
| Lequesne Knee Index (LKI) Subscore | To evaluate the clinical performance of the CR 500™ by each Lequesne Knee Index (LKI) subscore Lequesne Knee Index Score: minimum index score: 0 maximum index score: 24 0 means none OA >= means extremely severe OA | 4 weeks | 
| Symptoms Variation in terms of Lequesne Knee Index (LKI) score | To evaluate the clinical performance of the CR 500™ in the attenuation of symptoms in patients affected by KOA stratified by KOA severity as assessed by Lequesne Knee Index (LKI) score | 4 weeks | 
| Cluster of Subjective Symptoms evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire | To evaluate the different dimensions of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire Koos converted into a 0-100 Score 0 means worst level of OA 100 means best level of OA Subscores: Pain, Symptoms, Sports, Quality of Life, Activities of Daily Living | 4 weeks | 
| Number of participants with treatment-related adverse event as assessed by a questionnaire. | To evaluate the side effects of the product CR 500™ through a the completion of a specific questionnaire by the patient. | 4 weeks | 
| Product tolerability and patient satisfaction as assessed by a questionnaire using a five-points Likert scale | To evaluate the tolerability and patient satisfaction of the CR 500™ through a the completion of a specific questionnaire by the patient, the five-points Likert scale in which 1 means Strongly disagree with the assertion and 5 means Strongly agree | 4 weeks | 
| Evaluation of the status of the cartilage degradation by quantification of neoepitope of type II collagen (C2C) | Evaluation of the status of the cartilage degradation by quantification of neoepitope of type II collagen in synovial fluid by ELISA (ng/mL) | 4 weeks | 
| Evaluation of the status of the cartilage degradation by quantification of C-terminal telopeptide of type II collagen (CTX-II) | Evaluation of the status of the cartilage degradation by quantification of C-terminal telopeptide of type II collagen quantification (CTX-II) in synovial fluid by ELISA (pg/mL) | 4 weeks | 
| Evaluation of the status of the cartilage by quantification of type II collagen propeptide (CPII) quantification | Evaluation of the status of the cartilage by quantification of type II collagen propeptide (CPII) in synovial fluid by ELISA (ng/mL) | 4 weeks | 
| Evaluation of the status of the cartilage by quantification of hyaluronic acid (HA) quantification | Evaluation of the status of the cartilage by quantification of hyaluronic acid (HA) in synovial fluid by ELISA (mg/mL) | 4 weeks | 
| Evaluation of the inflammatory status of the knee joint by quantification of tumour necrosis factor (TNF) quantification | Evaluation of the status of the cartilage by quantification of tumour necrosis factor (TNF) in synovial fluid by ELISA (pg/mL) | 4 weeks | 
| Evaluation of the macrophages infiltration in the knee joint by quantification of Cluster of Differentiation 206 (CD206) | Evaluation of the macrophages infiltration in the knee joint by quantification of Cluster of Differentiation 206 (CD206) by Real Time Polymerase Chain Reaction (PCR) | 4 weeks | 
| Evaluation of the macrophages infiltration in the knee joint by quantification of Cluster of Differentiation 11c (CD11c) | Evaluation of the macrophages infiltration in the knee joint by quantification of Cluster of Differentiation 11c (CD11c) by Real Time PCR | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Knee osteoarthritis;, Hyaluronic acid, Peptides, Synovial fluid, Algofunctional scores, Biochemical markers, Macrophages infiltration