Post Marketing Clinical Follow up Study to Evaluate the Performance and Safety of ORTHIX PLUS

Post Marketing Clinical Follow up Study to Evaluate the Performance and Safety of ORTHIX PLUS for Pain Relief in Patients Suffering From Osteoarthritis or Degenerative Joint Diseases

This trial is a post marketing clinical follow up study, aiming to evaluate the performance and safety of ORTHIX PLUS for pain relief in patients suffering from osteoarthritis or degenerative joint diseases.

The study will involve 54 subjects, who will be enrolled in 2 centers in Turkey. The primary objective is to evaluate the overall performance of ORTHIX PLUS in providing relief in patients suffering from painful knee ostearthritis or degenerative joint diseases when used according to indications for use.

The first secondary objective is to evaluate the overall performance of ORTHIX PLUS in providing relief when used according to indications for use, at different time points. The other secondary objective is to evaluate the overall safety during the study period.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoarthritis, Knee; Degenerative Joint Disease of Knee

Detailed Description

Design:

Open, non-randomised, non-comparative, single group assignment, multicentre study.

Chronogram of visits:

The study foresees the following visits per patient:

Visit 1 day -3 to day -1: Screening. Visit 2 day 0: Baseline visit (1st injection). Visit 3 day 7 (± 1 day): Follow up visit and, 2nd injection. Visit 4 day 14 (± 2 days): Follow up visit and, 3rd injection. Visit 5 day 21 (± 2 days): Follow up visit. Visit 6 day 56 (± 2 days): Follow up visit. Visit 7 day 98 (± 2 days): Follow up visit. Visit 8 day 194 (± 4 days): Final visit.

Patient enrollment and allocation:

After informed consent signature, the patient is considered enrolled. Once the eligibility is established according to inclusion/exclusion criteria the patient will receive a unique patient code and will be allocated to ORTHIX PLUS® (the tested medical device). The Investigator must also complete a patient screening log, which reports on all patients who were seen to determine eligibility for inclusion in the study.

Statistical Analysis:

The protocol outlines that a two-sided p-value of 0.05 or less will be used to declare statistical significance for all analyses. Similarly, all confidence intervals will be calculated at the 95% level.

No adjustment for multiplicity will be made to adjust type 1 error rate for secondary endpoints. If necessary, relevant results from other studies already reported in the literature will be considered in the interpretation of results.

The final analysis will be completed after all patients have been exited the study, all queries resolved, and the database have been locked.

If a patient is missing information for one or more variables, the missing data will not be replaced. Quantitative variables (i.e., demographic) if normally distributed will be described through media, standard deviation (SD); variables non-normally distributed will be described using median and range of interquartile.

Considering this clinical trial's design as a longitudinal cohort study, the focus of the performed statistical assessments will be the longitudinal (statistical) analysis.

Primary endpoint, change in Knee injury and Osteoarthritis Outcome Score(KOOS) pain sub-scale score from baseline to 14 weeks visit, will be analysed by performing a Student's t-test for paired data, or a Wilcoxon signed rank test if major deviations from former's test assumptions are recorded. As no missing data imputation on the primary outcome is planned, if such cases arise, a Linear Mixed Model analysis will be performed, to make use of the complete ITT(Intention to treat) population.

Secondary endpoints, all continuous variables in nature, will be assessed by performing ANOVA for repeated measures tests, or ANCOVA for repeated measures tests (if considering covariates like age, sex, BMI, etc.), assuming completeness of data (no missing data). If missingness of data drastically reduces the sample size (e.g., > 5% of patients will be eliminated), a robust statistical analysis method will be employed instead. Such a method, Linear Mixed Models analysis, has the main advantage of making use of the complete ITT population.

The safety analysis will be done on the ITT population.

• Study Type: Observational
• Enrollment (Anticipated): 54

Contacts and Locations

• Study Contact: Name: Franco Barattini, MD; Phone Number: +39 335 5437574; Email: franco.barattini@tigermedgrp.com
• Study Contact Backup: Name: Ioana Gâlcă, CPM; Phone Number: +40 741 107 508; Email: ioana.galca@tigermedgrp.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients from the two Turkish primary care clinics

Description

Inclusion Criteria:

• Patients older than 18 years old(inlcusive≥18years).
• Men or women.
• Patients suffering from painful chronic idiopathic symptomatic degenerative joint diseases(clinical evidence) OR knee osteoarthritis (as defined by the American College of Rheumatology (ACR) criteria); for patients with osteoarthritis at both knees, only the most painful one will be included in the study.
• VAS knee pain≥40mm at screening and 30 days before.
• Patients willing and able to comply with study terms.
• Patients willing to discontinue all other degenerative joint diseases or knee osteoarthritis treatments.

Exclusion Criteria:

• Patients that are unable or unwilling to provide informed consent and/or patients participating in a concurrent clinical trial and/or patients that have participated in a similar clinical trial within the last 30 days.
• Patients with known hypersensitivity to any components of investigational product.
• Patients with infected or severely inflamed joints
• Patients with skin diseases or infections in the area of the injection site.
• Patients with hepatic failure or history thereof.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KOOS for Pain at 12 weeks	• Functional assessment of HYALEXO® by KOOS (Knee Injury and Osteoarthritis Outcome score) for Pain subscale at 12 weeks after the last administration of the investigational product, compared to the baseline. This was the endpoint used for the sample size calculation.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KOOS for Symptoms, Activity of Daily Living, Sport and Recreation and knee related Quality of life	Functional Assessment of HYALEXO® by KOOS for other Symptoms, Activity of Daily Living (ADL), Sport and Recreation (Sport/Rec) function and knee related Quality of life (QoL) at 1, 6, 12 weeks and 6 months after the last administration of the investigational product, compared to baseline	1,6,12 weeks and 6 months
KOOS for Pain at 1, 6 weeks and 6 months	Functional Assessment of HYALEXO® by KOOS for Pain subscale at 1, 6 weeks and 6 months after the last administration of the investigational product, compared to baseline.	1, 6 weeks and 6 months
Weight-bearing pain using a Visual Analogue Scale(VAS)	Changes in the weight-bearing pain using a Visual Analogue Scale (100 mm - VAS) at 1, 6, 12 weeks and 6 months after the last administration, compared to the baseline.	1,6,12 weeks and 6 months
Changes is rest pain(VAS)	Changes in the rest pain (100 mm - VAS) at 1, 6, 12 weeks and 6 months after the last administration, compared to the baseline.	1,6,12 weeks and 6 months
Changes in motion pain(VAS)	Changes in the motion pain (pain after 15 m walk) (100 mm - VAS) at 1, 6, 12 weeks and 6 months after the last administration, compared to the baseline.	1,6,12 weeks and 6 months
Global Pain Assessment	Patient Global Pain Assessment (100 mm - VAS) at 1, 6, 12 weeks and 6 months after the last administration, compared to the baseline.	1,6,12 weeks and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Safety endpoints	Safety checklist for local reactions at the injection site (i.e. discomfort, transient pain) at baseline and at all follow up visits	baseline(day0), all follow up visit(day7,14,21,56,98)
Secondary Safety endpoints	AE/ADE/SAE/SADE/USADE/DD searching and assessment at all visits	all visit(screening, baseline, day7,14,21,56,98,194)

Collaborators and Investigators

• Sponsor: Yooyoung Pharmaceutical Co., Ltd.
• Collaborators: Opera CRO, a TIGERMED Group Company
• Investigators: Principal Investigator: Yüksel Ersoy, Dr, İnönü University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation; Principal Investigator: Serpil Tuna, Dr, AKDENİZ University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

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

Drug and device information, study documents

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