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Pilot, Prospective, Comparative Multicentric Study Evaluating the Effects on the Arthrosis Biomarkers, the Clinical Effectiveness, the Tolerance of an Intra-articular Injection of Hyaluronic Acid KARTILAGE CROSS Versus Placebo in Patients Suffering From Knee Osteoarthritis (EPIKART)

Primary Purpose

Knee Osteoarthritis

Status

Completed

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

KARTILAGE CROSS

PLACEBO

About this trial

This is an interventional treatment trial for Knee Osteoarthritis

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Man or Women, aged from 45 to 80
Presenting a symptomatic femoro-tibial knee osteoarthritis responding to clinical and radiologic ACR (American College of Rheumatology) criteria,
Symptomatic since at least 6 months
Mean global knee pain determined on Visual Analog Scale for the last 24 hours over 40 mm (without any NSAIDs or analgesics for more than 48 hours).
Kellgren and Lawrence (K&L) radiological stage must have been II or III on pictures lasted less than 12 months
Requiring a treatment with hyaluronic acid after failure or intolerance to first line analgesics or NSAIDs
Having signed an informed consent after receiving comprehensive information
Capable to follow the study instructions
Benefiting from health insurance.

Exclusion Criteria:

Related to the osteoarthritis pathology:

Significant clinical knee effusion
Radiographical Kellgren and Lawrence grade I or IV
Osteoarthritis secondary to a microcrystalline arthropathy: chondrocalcinosis previously known or defined by a calcium border on at least one tibiofemoral spacing, gout ...
Isolated femoropatellar osteoarthritis
Presence of another joint (other than the evaluated knee) affected by osteoarthritis (known and symptomatic): collateral knee, hip, hand, shoulder, ankle or foot
Chondromatosis or villonodular synovitis of the knee
Paget disease
Recent trauma (< 1 month) of the evaluated knee
Pathologies interfering with the evaluation of osteoarthritis (microcrystalline inflammatory arthropathy, rheumatoid arthritis, radiculalgia in the lower limbs, arteritis. etc)
Acute inflammatory osteoarthritis (Kofus ≥ 7)

Related to previous and concomitant treatments

Corticosteroids injection in the last month before injection regardless the concerned joint
Hyaluronan injection in the last 6 months before injection regardless the concerned joint
Analgesics and NSAIDs intake during the last 48 hours before inclusion visit
Change in the dosage of slow-acting drugs against arthrosis i.e. chondroitin, glucosamine, diacerein or avocado-soybean unsaponifiables in the last 3 months before inclusion or planned during study
Arthroscopy or surgery in the target knee in the last 3 months before inclusion
Oral corticotherapy

Related to associated pathologies

Severe diseases (severe hepatic failure, renal failure, uncontrolled cardiovascular diseases….)
Dermatological infection at the site of injection
Anticoagulant treatment
Risk of hemorrhage according to the evaluator or injector assessment

Related to the patients

Known allergy to hyaluronan
Known allergy to acetaminophen
Known allergy to mannitol
Pregnant or breastfeeding women
Premenopausal women without contraception
Patient unable to read, and to write
Patient having participated in a clinical research investigation in the last 3 months
Patient under guardianship or judicial protection

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

KARTILAGE CROSS

Placebo

Arm Description

Kartilage® Cross (2.2 mL, 16 mg/g of hyaluronic acid)

Saline solution (2.2-2.5 mL, NaCl 9 mg/g)

Outcomes

Primary Outcome Measures

Percentage of patient with a reduction of at least 10 nmol/l of serum Coll2-1 between inclusion visit (10 days before injection) and 3 months after injection.

Secondary Outcome Measures

Variation in Coll2-1 between inclusion and 1 month or 6 months;

Variation of Lequesne index (LI) between inclusion visit and further visits

Variation in the global assessment of pain with visual analog scale (0-100 mm) between inclusion visit and further visits,

Percentage of responders according to OMERACT/OARSI (Outcome Measures in Rheumatoid Arthritis Clinical Trials/Osteoarthritis Research Society International) at 3 months and 6 months

Acetaminophen and Nonsteroidal anti-inflammatory drugs (NSAID) consumption during the study

Patient's global assessment of the disease activity

Monitoring of adverse events

Full Information

NCT ID

NCT02951585

First Posted

October 28, 2016

Last Updated

October 28, 2016

Sponsor

Laboratoires Vivacy

Collaborators

Artialis

1. Study Identification

Unique Protocol Identification Number

NCT02951585

Brief Title

Pilot, Prospective, Comparative Multicentric Study Evaluating the Effects on the Arthrosis Biomarkers, the Clinical Effectiveness, the Tolerance of an Intra-articular Injection of Hyaluronic Acid KARTILAGE CROSS Versus Placebo in Patients Suffering From Knee Osteoarthritis

Acronym

EPIKART

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Completed

Study Start Date

May 2013 (undefined)

Primary Completion Date

September 2014 (Actual)

Study Completion Date

October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Laboratoires Vivacy

Collaborators

Artialis

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Intra-articular hyaluronic acid injections, also known as viscosupplementation, are a treatment option for knee osteoarthritis that serves to restore the decreasing rheological properties of synovial fluid. KARTILAGE® CROSS is a visco-elastic gel of highly purified reticulated hyaluronic acid. It contains mannitol to provide an anti-oxidative action and to avoid hyaluronic acid depolymerization. Reticulation and mannitol increase the residency time of the product in the joint cavity then allowing a single injection in painful knee osteoarthritis patients. The US food and drugs administration (FDA) and European medicine agency (EMA), have recently published guidelines recommending a higher level of integration of biomarkers in the development and testing of new drugs to advance decision-making on dosing, time and treatment effect, trial design, and risk/benefit analysis. Biomarkers can be used not only in the process of drug development, but also in the future in assessment of individual patient's response to treatment. Several soluble biomarkers have been identified as potential candidates to predict or monitor the efficacy of intervention. Coll2-1, a degradation product of type II collagen, and Coll2-1NO2, a nitrated form of the Coll2-1 peptide have been studied in human osteoarthritis and entered the qualification process. Evidences demonstrated them to be pertinent and to be foresee as markers used for the diagnosis, the prognosis, the burden of disease and the monitoring of a treatment efficacy. The aim of this study was to provide with the first kinetic data regarding biomarkers in painful knee osteoarthritis patients treated with a new reticulated hyaluronic acid. The effects of the treatment were compared to those of saline solution. The primary endpoint was a specific osteoarthritis biomarker, Coll2-1. The secondary endpoints were the effects of the treatment or placebo on other biomarkers of osteoarthritis, its clinical efficacy and tolerance

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Knee Osteoarthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

81 (Actual)

8. Arms, Groups, and Interventions

Arm Title

KARTILAGE CROSS

Arm Type

Experimental

Arm Description

Kartilage® Cross (2.2 mL, 16 mg/g of hyaluronic acid)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Saline solution (2.2-2.5 mL, NaCl 9 mg/g)

Intervention Type

Device

Intervention Name(s)

KARTILAGE CROSS

Intervention Description

Intra-articular injection of Kartilage Cross

Intervention Type

Device

Intervention Name(s)

PLACEBO

Intervention Description

Intra-articular injection of physiological serum (saline solution)

Primary Outcome Measure Information:

Title

Percentage of patient with a reduction of at least 10 nmol/l of serum Coll2-1 between inclusion visit (10 days before injection) and 3 months after injection.

Time Frame

3 months after injection

Secondary Outcome Measure Information:

Title

Variation in Coll2-1 between inclusion and 1 month or 6 months;

Time Frame

1 month and 6 months

Title

Variation of Lequesne index (LI) between inclusion visit and further visits

Time Frame

1 month, 3 months and 6 months

Title

Variation in the global assessment of pain with visual analog scale (0-100 mm) between inclusion visit and further visits,

Time Frame

1 month, 3 months and 6 months

Title

Percentage of responders according to OMERACT/OARSI (Outcome Measures in Rheumatoid Arthritis Clinical Trials/Osteoarthritis Research Society International) at 3 months and 6 months

Time Frame

3 months and 6 months

Title

Acetaminophen and Nonsteroidal anti-inflammatory drugs (NSAID) consumption during the study

Time Frame

1 month, 3 months and 6 months

Title

Patient's global assessment of the disease activity

Time Frame

1 month, 3 months and 6 months

Title

Monitoring of adverse events

Time Frame

1 month, 3 months and 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Man or Women, aged from 45 to 80 Presenting a symptomatic femoro-tibial knee osteoarthritis responding to clinical and radiologic ACR (American College of Rheumatology) criteria, Symptomatic since at least 6 months Mean global knee pain determined on Visual Analog Scale for the last 24 hours over 40 mm (without any NSAIDs or analgesics for more than 48 hours). Kellgren and Lawrence (K&L) radiological stage must have been II or III on pictures lasted less than 12 months Requiring a treatment with hyaluronic acid after failure or intolerance to first line analgesics or NSAIDs Having signed an informed consent after receiving comprehensive information Capable to follow the study instructions Benefiting from health insurance. Exclusion Criteria: Related to the osteoarthritis pathology: Significant clinical knee effusion Radiographical Kellgren and Lawrence grade I or IV Osteoarthritis secondary to a microcrystalline arthropathy: chondrocalcinosis previously known or defined by a calcium border on at least one tibiofemoral spacing, gout ... Isolated femoropatellar osteoarthritis Presence of another joint (other than the evaluated knee) affected by osteoarthritis (known and symptomatic): collateral knee, hip, hand, shoulder, ankle or foot Chondromatosis or villonodular synovitis of the knee Paget disease Recent trauma (< 1 month) of the evaluated knee Pathologies interfering with the evaluation of osteoarthritis (microcrystalline inflammatory arthropathy, rheumatoid arthritis, radiculalgia in the lower limbs, arteritis. etc) Acute inflammatory osteoarthritis (Kofus ≥ 7) Related to previous and concomitant treatments Corticosteroids injection in the last month before injection regardless the concerned joint Hyaluronan injection in the last 6 months before injection regardless the concerned joint Analgesics and NSAIDs intake during the last 48 hours before inclusion visit Change in the dosage of slow-acting drugs against arthrosis i.e. chondroitin, glucosamine, diacerein or avocado-soybean unsaponifiables in the last 3 months before inclusion or planned during study Arthroscopy or surgery in the target knee in the last 3 months before inclusion Oral corticotherapy Related to associated pathologies Severe diseases (severe hepatic failure, renal failure, uncontrolled cardiovascular diseases….) Dermatological infection at the site of injection Anticoagulant treatment Risk of hemorrhage according to the evaluator or injector assessment Related to the patients Known allergy to hyaluronan Known allergy to acetaminophen Known allergy to mannitol Pregnant or breastfeeding women Premenopausal women without contraception Patient unable to read, and to write Patient having participated in a clinical research investigation in the last 3 months Patient under guardianship or judicial protection

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28549430

Citation

Henrotin Y, Berenbaum F, Chevalier X, Marty M, Richette P, Rannou F. Reduction of the Serum Levels of a Specific Biomarker of Cartilage Degradation (Coll2-1) by Hyaluronic Acid (KARTILAGE(R) CROSS) Compared to Placebo in Painful Knee Osteoarthritis Patients: the EPIKART Study, a Pilot Prospective Comparative Randomized Double Blind Trial. BMC Musculoskelet Disord. 2017 May 26;18(1):222. doi: 10.1186/s12891-017-1585-2.

Results Reference

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