Osteoarthritis, KneeENKORENCT03762408
Efficacy and Safety of a Intra-articular Injection, ENKO1, in Patients With Symptomatic Knee Osteoarthritis.
A study testing ENKO 1 and Durolane in people with Osteoarthritis, Knee, run by OPKO Health, Inc. at 18 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- ENKO 1 and Durolane
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 175 participants
- Where
- 18 sitesSpain
- Study dates
- 15 Dec 2017to 29 May 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
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- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Spain18 sites
Instituto Médico Arriaza
A Coruña, 15009
Hospital del Mar
Barcelona, 08003
Instituto POAL del Reumatología
Barcelona, 08022
Hospital Sant Rafael
Barcelona, 08035
Hospital Clínic de Barcelona
Barcelona, 08036
Clínica Novo Sancti Petri
Chiclana de la Frontera, Cádiz, 11139
Clínica Diagonal
Esplugues de Llobregat, Barceloma, 08950
Consell calatà de l'Esport
Esplugues de Llobregat, Barcelona, 08950
BiClinic
Madrid, 28027
AMS Centro Médico del Ejercicio
Málaga, 29004
Clínica Dr. Casermeiro
Mijas Costa, Málaga, 29651
Clínica ISMEC
Seville, 41001
Consorci Sanitari de Terrassa
Terrassa, Barcelona, 08227
Clínica IQTRA
Torrejón de Ardoz, Madrid, 28002
Hospital de Torrelodones
Torrelodones, Madrid, 28250
Clínica Gastaldi
Valencia, 46015
Clínica Traumatológica Dr. Baró
Valladolid, 47004
Hospital Vithas San José
Vitoria-Gasteiz, 01008
About this study
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.
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.
- Conditions
- Osteoarthritis, Knee
- Being tested
- ENKO 1, Durolane
- Keywords
- Osteoarthritis, Knee, Chondroitin Sulfate, Hyaluronic Acid, Intra-articular Injection, Viscosupplementation, Pain Relief, Biomarkers
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENKO 1Device
50 mg of HA/ 50 mg of CS in 5 ml
DurolaneDevice
60 mg HA crosslinked in 3 ml
| Study group | Role | What they receive |
|---|---|---|
| ENKO 1 | Experimental | ENKO 1 administered by single intra-articular injection. Receives: Device: ENKO 1 |
| Durolane | Active comparator | Durolane administered by single intra-articular injection. Receives: Device: Durolane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Relief
Assessed using VAS (Visual Analogue Scale) Huskisson 0-100mm
Pain relief scored on a scale of 0 to 10.
0 means No pain and 10 means worst possible pain.
Measured: Change from baseline pain relief at 6 months.
Secondary outcomes (11)
Pain Relief
Assessed using VAS (Visual Analogue Scale) Huskisson 0-100mm
Pain relief scored on a scale of 0 to 10.
0 means No pain and 10 means Worst possible pain.
Measured: 0, 1, 6 and 12 weeks.
Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Pain subscale)
Validated questionnaire for patients with osteoarthritis of the knee. 5 items: during walking, using stairs, in bed, sitting or lying, and standing upright.
The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4).
The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Usually a sum of the scores for all three subscales gives a total WOMAC score.
Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Measured: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Stiffness subscale)
Validated questionnaire for patients with osteoarthritis of the knee. 2 items: after first waking and later in the day. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4).
The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Usually a sum of the scores for all three subscales gives a total WOMAC score.
Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Measured: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Functional capacity subscale)
Validated questionnaire for patients with osteoarthritis of the knee. 17 items): using stairs, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy domestic duties, light domestic duties.
The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4).
The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Usually a sum of the scores for all three subscales gives a total WOMAC score.
Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Measured: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of percentage of patients who respond to treatment
Evaluation of percentage of patients who respond to treatment according to the OMERACT-OARSI criteria.
Measured: 0, 1, 6, 12 and 24 weeks.
Global evaluation of the activity of the disease and of the respond to treatment by patient.
Global evaluation of the activity of disease by the patient (VAS (Visual Analogue Scale) from 0-100mm).
Scale from 0 to 10, which correspond to: Mild (0-2), Moderate (3-7) and Intense (8-10).
where 0 is better outcome and 10 is the worst outcome.
Measured: 0, 1, 6, 12 and 24 weeks.
Evaluation of Health status of patients
Evaluation of Health status by quality of life questionnaire 12-Item Short Form Survey (SF-12).
It consists of 12 items from the 8 dimensions of the SF-36 Physical Function, Social Function, Physical Role, Emotional Role, Mental Health, Vitality, Body Pain, General Health and evaluate intensity and frequency of each item.
Scale ranges: Minimum 12 and maximum 60 scores. When 12 means better and 60 is the worse outcome.
Measured: 0, 1, 6, 12 and 24 weeks.
Evaluation of concomitant medication intake
Daily intake of Paracetamol (maximum 3g/day)
Measured: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of synovitis
Clinical valoration of synovial joint swelling.
Measured: -7, 0, 1, 6, 12 and 24 weeks.
Biomarkers
Blood sample analysis of serum soluble biomarkers according to current validation by THE BIOMARKERS CONSORTIUM.
Pre-selected biomarkers: Concentration of Serum CTXI, Serum NTXI, Serum-HA, Serum-PIIANP and Serum CTXII.
Measured: -7 and 12 weeks
Adverse events
Number of Participants with any Adverse event.
Measured: 0, 1, 6, 12 and 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2018
- Study start15 Dec 2017
- Primary completion29 May 2020
- Study completion29 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- OPKO Health, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Osteoarthritis Foundation International (OAFI)
- Responsible party
- Sponsor
- Investigators
- Luisa Varela, Ph, MSc, Study chair, OPKO Health, Inc.Jordi Monfort, MD, PhD, Principal investigator, Hospital del Mar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03762408
- Sponsor's protocol ID
- OPK-ENK-2017-01
- Acronym
- ENKORE
- Status last verified
- Mar 2021
- First submitted
- 28 Nov 2018
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03762408
- Acronym / sponsor ID
- ENKORE / OPK-ENK-2017-01
- Conditions
- Osteoarthritis, Knee
- Keywords
- Osteoarthritis, Knee, Chondroitin Sulfate, Hyaluronic Acid, Intra-articular Injection, Viscosupplementation, Pain Relief, Biomarkers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- OPKO Health, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Osteoarthritis Foundation International (OAFI)
- Study start
- 15 Dec 2017 (actual)
- Primary completion
- 29 May 2020 (actual)
- Study completion
- 29 May 2020 (actual)
- First posted
- 3 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ENKO 1 | Experimental | Device: ENKO 1ENKO 1 administered by single intra-articular injection. |
| Durolane | Active comparator | Device: DurolaneDurolane administered by single intra-articular injection. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (34 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ENKO 150 mg of HA/ 50 mg of CS in 5 ml | Device | ENKO 1 |
| Durolane60 mg HA crosslinked in 3 ml | Device | Durolane |
Primary outcome
Pain Relief
Time frame: Change from baseline pain relief at 6 months.
Assessed using VAS (Visual Analogue Scale) Huskisson 0-100mm Pain relief scored on a scale of 0 to 10. 0 means No pain and 10 means worst possible pain.
11 secondary outcomes
Pain Relief
Time frame: 0, 1, 6 and 12 weeks.
Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Pain subscale)
Time frame: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Stiffness subscale)
Time frame: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of functional WESTERN ONTARIO AND MCMASTER OSTEOARTHRITIS INDEX (WOMAC) index score (Functional capacity subscale)
Time frame: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of percentage of patients who respond to treatment
Time frame: 0, 1, 6, 12 and 24 weeks.
Global evaluation of the activity of the disease and of the respond to treatment by patient.
Time frame: 0, 1, 6, 12 and 24 weeks.
Evaluation of Health status of patients
Time frame: 0, 1, 6, 12 and 24 weeks.
Evaluation of concomitant medication intake
Time frame: -7, 0, 1, 6, 12 and 24 weeks.
Evaluation of synovitis
Time frame: -7, 0, 1, 6, 12 and 24 weeks.
Biomarkers
Time frame: -7 and 12 weeks
Adverse events
Time frame: 0, 1, 6, 12 and 24 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luisa Varela, Ph, MSc study chair
OPKO Health, Inc.
Jordi Monfort, MD, PhD principal investigator
Hospital del Mar
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ENKO 1 and Durolane in people with Osteoarthritis, Knee, run by OPKO Health, Inc. at 18 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Relief (time frame: Change from baseline pain relief at 6 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2021.