Clinical trial NCT03762408: Efficacy and Safety of a Intra-articular Injection, ENKO1, in Patients With Symptomatic Knee Osteoarthritis.
Official title: Comparative Study of the Efficacy and Safety of an Intra-articular Injection of ENKO 1 vs Durolane in Patients With Symptomatic Osteoarthritis of the Knee.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: Osteoarthritis
Knee
Chondroitin Sulfate
Hyaluronic Acid
Intra-articular Injection
Viscosupplementation
Pain Relief
Biomarkers
Lead sponsor: OPKO Health, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Osteoarthritis Foundation International (OAFI)
First posted: 2018-12-03
Enrollment: 175
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clinical trial with medical device, multicenter, single-blind (blind third party evaluation), randomized, comparative and in two paralell groups, to demonstrate the treatment according to usual clinical practice, of the combination of 50 mg Sodium Hyaluronate and 50 mg Chondroitin Sulfate (ENKO 1) in a single administration, has non-inferiority efficacy vs the comparator (Durolane; 60 mg HA crosslinked) in patients with symptomatic knee osteoarthritis after three months of follow-up.


Eligibility criteria: Inclusion Criteria:

* Medial femorotibial compartment knee OA.
* Fulfilment of ACR criteria for knee OA (knee pain + grinding + stiffness in the morning \< 30 minutes).
* Patients with a clinical course of disease longer than 6 months.
* Global pain score greater than 60 mm on a 0-100 mm VAS on the knee under study.
* Grade II or III according to the Kellgren and Lawrence classification system for the knee under study (on a posteroanterior X-ray performed under weight-bearing and for 6 months before randomisation).
* Patients taking analgesics for at least 3 months before randomisation and whom are dissatisfied with their current therapy.
* Patients who have given their consent in writing to take part in the study.
* Woman of childbearing age must take a urine pregnancy test which must be negative at the randomisation visit and be currently using an effective contraceptive method for at least 2 menstrual cycles (oral contraceptives, intrauterine device, tubal ligation or other effective procedures).

Exclusion Criteria:

* Isolated symptomatic patellofemoral osteoarthritis.
* Microcrystalline osteoarthritis.
* Prosthesis in knee under study.
* Joint lavage or arthroscopy or any surgery on the knee under study in the 6 months before randomisation.
* Paget's disease of bone, chondromatosis or villonodular sinovitis.
* Inflammatory, infectious or metabolic arthritis (rheumatoid arthritis, spondyloarthropathy or connective tissue diseases).
* Haemochromatosis, ochronosis or haemophilia.
* History of diseases that the investigator considers likely to interfere with the functional disability assessment.
* Knee surgery planned during the study period.

Other disease-related criteria:

* BMI greater than or equal to 30.
* Immunodeficiency or a serious or progressive disease (heart, lung, liver, kidney, haematological, neoplastic or infectious disease).
* Skin diseases or infections in the area of the injection site.
* Previous history of venous thromboembolism (including pulmonary embolism) or high risk of venous thromboembolism.
* Venous or lymphatic stasis of the leg under study.
* Severe acute or chronic disease that the investigator considers incompatible with the conduct of the study.
* Disease that the investigator considers likely to interfere with the study results or to expose the patient to an additional risk.
* Alcohol or drug abuse or dependence.

Previous or concomitant treatment-related criteria:

* Patients who have taken a SYSADOA, SERM or a drug/dietary supplement containing glucosamine, chondroitin sulfate, diacerein or avocado-soybean extracts in the 3 months before randomisation
* Patients who have taken paracetamol in the 24 hours before randomisation or any other symptomatic analgesic drug, including NSAIDs (except aspirin up to 325 mg/day for cardiovascular prophylaxis), in the 48 hours before randomisation
* Patients who have received any corticosteroid treatment by any route of administration (other than inhalers or the ocular or auricular routes) in the month before randomisation
* Patients who have received an intra-articular steroid injection in the knee under study in the month before randomisation or patients who have received intra-articular hyaluronic acid in the target knee in the 6 months before randomisation
* Patients who have received any local or topical treatment on the target knee in the 2 weeks before randomisation

Criteria related to concomitant medication:

* Hypersensitivity to paracetamol or NSAIDs

Study product-related criteria:

* Known allergy to the study treatments or to any of its ingredients.

Other criteria:

* Patients likely to be unable to comply with the protocol instructions and/or treatment, in the investigator's opinion
* Patients who have taken part in a clinical trial in the preceding 2 months or taking part in a trial at the time of randomisation
* Patients linguistically or mentally incapable of understanding the nature, objectives and possible consequences of the study; or who refuse to be subject to its limitations
* Patients who are family or colleagues (secretary, nurse, technician, etc.) of the investigator.
* Women: pregnant or breastfeeding

Primary outcomes:
measure: Pain Relief
timeFrame: Change from baseline pain relief at 6 months.
Secondary outcomes:
measure: Pain Relief
timeFrame: 0, 1, 6 and 12 weeks.
measure: Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Pain subscale)
timeFrame: -7, 0, 1, 6, 12 and 24 weeks.
measure: Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Stiffness subscale)
timeFrame: -7, 0, 1, 6, 12 and 24 weeks.
measure: Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Functional capacity subscale)
timeFrame: -7, 0, 1, 6, 12 and 24 weeks.
measure: Evaluation of percentage of patients who respond to treatment
timeFrame: 0, 1, 6, 12 and 24 weeks.
measure: Global evaluation of the activity of the disease and of the respond to treatment by patient.
timeFrame: 0, 1, 6, 12 and 24 weeks.
measure: Evaluation of Health status of patients
timeFrame: 0, 1, 6, 12 and 24 weeks.
measure: Evaluation of concomitant medication intake
timeFrame: -7, 0, 1, 6, 12 and 24 weeks.
measure: Evaluation of synovitis
timeFrame: -7, 0, 1, 6, 12 and 24 weeks.
measure: Biomarkers
timeFrame: -7 and 12 weeks
measure: Adverse events
timeFrame: 0, 1, 6, 12 and 24 weeks.
Other outcomes:
Locations:
city: Esplugues De Llobregat
country: Spain
facility: Clínica Diagonal
state: Barceloma
city: Esplugues De Llobregat
country: Spain
facility: Consell calatà de l'Esport
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Chiclana de la Frontera
country: Spain
facility: Clínica Novo Sancti Petri
state: Cádiz
city: Torrejón De Ardoz
country: Spain
facility: Clínica IQTRA
state: Madrid
city: Torrelodones
country: Spain
facility: Hospital de Torrelodones
state: Madrid
city: Mijas Costa
country: Spain
facility: Clínica Dr. Casermeiro
state: Málaga
city: A Coruña
country: Spain
facility: Instituto Médico Arriaza
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Instituto POAL del Reumatología
city: Barcelona
country: Spain
facility: Hospital Sant Rafael
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: BiClinic
city: Málaga
country: Spain
facility: AMS Centro Médico del Ejercicio
city: Sevilla
country: Spain
facility: Clínica ISMEC
city: Valencia
country: Spain
facility: Clínica Gastaldi
city: Valladolid
country: Spain
facility: Clínica Traumatológica Dr. Baró
city: Vitoria Gasteiz
country: Spain
facility: Hospital Vithas San José
Study officials:
affiliation: OPKO Health, Inc.
name: Luisa Varela, Ph, MSc
role: STUDY_CHAIR
affiliation: Hospital del Mar
name: Jordi Monfort, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: