A Study to Evaluate the Clinical Performance and Safety of an Intra-articular Hyaluronic Acid in Knee Osteoarthritis
- Conditions
- Knee Osteoarthritis
- Interventions
- Device: Placebo
- Registration Number
- NCT03200288
- Lead Sponsor
- IBSA Institut Biochimique SA
- Brief Summary
This is a study to evaluate the Clinical Performance and Safety of a single intra-articular (i.a.) injection of hyaluronic acid product (as HL-01) in the treatment of pain due to osteoarthritis (OA) of the knee.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 692
- Female and male subjects ≥40 to 80 years of age.
- Subjects with primary knee OA of the medial or lateral femoro-tibial compartment, documented according to ACR criteria with symptoms, at screening, from at least 3 months.
- Subjects with Kellgren & Lawrence (K-L) radiological grade 2-3.
- Subjects with at least one antero-posterior view X-Ray image of the target knee taken within 12 months prior to the screening.
- Subjects with OA pain intensity meeting the criteria below:
If unilateral knee OA: Subjects demonstrating at screening pain intensity in the target knee measured by Visual Analogue Scale (VAS) ≥40 mm VAS, and ≤ 20 mm in the contralateral knee and confirmed at randomization after wash-out from analgesics/NSAIDs.
If bilateral knee OA: definition of the most symptomatic joint at screening based on subject's evaluation and Investigator's clinical judgment with subjects demonstrating pain intensity in the target knee measured by Visual Analogue Scale (VAS) ≥40 mm VAS, and ≤ 20mm in the contralateral knee and confirmed at randomization after wash-out from analgesics/NSAIDs.
- Subjects are able to understand and are willing and able to comply with study procedures including usage of acetaminophen as the only analgesic.
- Subjects are able to provide informed consent.
- Any female subject of childbearing potential must agree to use adequate methods of contraception throughout the course of the study.
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Subjects with secondary (post-traumatic) knee OA of the target and non-target joints.
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Subjects with K-L radiological grade 4 knee OA.
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Subjects with a history of knee joint replacement/arthroplasty of the target knee.
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Subjects with a history of arthroscopy, osteotomy, or surgery of the target knee in the past 12 months.
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Subjects with any significant injury to the target knee in the last 6 months (as per Investigator judgment).
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Subjects with Body Mass Index (BMI) ≥32 kg/m2.
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Subjects with any musculoskeletal condition affecting the target knee that would impair proper assessment of the Investigational Medicinal Device (IMD) performance in the target knee as assessed by the Investigator and such as:
- severe varus/valgus deformity (>15°)
- predominantly patello-femoral pain/syndrome.
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Subjects with a history of symptomatic hip OA or other health condition i.e. associated with pain and interfering with adequate study endpoints evaluation.
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Subjects with a known history or present evidence of conditions which may affect the target knee assessments, like rheumatic disease and inflammatory, infective or metabolic joint diseases; recurrent clinical chondrocalcinosis; crystal arthropathies; osteo-articular pathologies differing from arthrosis; articular fracture; ochronosis; acromegaly; haemochromatosis; Wilson's disease; primary osteochondromatosis; heritable disorders; collagen gene mutations.
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Subjects with venous or lymphatic stasis in the relevant limb.
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Subjects with a history of the following treatments for knee OA:
a) I. a. knee corticosteroids: i. target knee - in the past 3 months ii. non-target knee/other joints - in the past 4 weeks b) Systemic (both oral and parenteral) and topical corticosteroids at the target knee in the past 3 months.
c) Topical anti-inflammatories and analgesics applied at the target knee in the past 48 hrs.
d) Viscosupplementation with hyaluronic acid or joint-lavage in the target knee in the past year.
e) Physical therapy started in the last 3 months in the target knee. f) Symptomatic Slow-Acting Drugs for OA (SYSADOA) such as glucosamine, chondroitin sulfate, diacerhein, or other medications like avocado/soya extracts, etc. in the past 3 months.
g) Chronic or recurrent use of narcotic analgesics. h) Use of analgesic (other than acetaminophen) and NSAIDs for a time of 5-half-lives before the screening.
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Subjects with a history of chronic or recurrent use of NSAIDs/analgesics/narcotics because of diseases different from OA of the target knee.
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Subjects treated with drugs having an influence on pain: hypnotics, muscle relaxants, anxiolytics if the intake has started less than 8 days before the screening.
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Subjects who currently use heparin or anti-vitamin K (e. g. crystalline warfarin) anticoagulant therapy.
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Subjects with the presence of infection, skin diseases, other disease or trauma in the area of the injection site or joint.
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Subjects with a known history or suspected allergy or hypersensitivity to hyaluronic acid or to hyaluronate preparations.
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Subjects with a known history or suspected allergy or hypersensitivity to acetaminophen.
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Subjects with any major surgery scheduled in the next 6 months.
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Subjects who have participated in a clinical study / investigation in the last 3 months.
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Pregnant or lactating women and women of childbearing potential not willing to use adequate contraception.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Single 2 ml intra-articular injection of Placebo (physiological solution)
- Primary Outcome Measures
Name Time Method Change in VAS (Visual Analogue Scale) pain score Baseline-week 24 The primary efficacy variable will be the change from baseline of the VAS pain score calculated as a VAS measure ranging from 0 to 100 mm. A four- step analysis will be followed in order to assess superiority of HL-01 versus Placebo after 6, 12, 18 and 24 weeks.
- Secondary Outcome Measures
Name Time Method Change in global status assessed by physician Baseline -Week 24 Change from baseline in global status assessed by physician at 6, 12, 18 and 24 weeks (5-point verbal Likert scale), dichotomised to 'Improvement' and 'No change/Worsening'
Change in global status assessed by subject (EQ-5D-5L EuroQol Group Health questionnaire) Baseline-Week 24 Change from baseline in global status assessed by subject at 6, 12, 18 and 24 weeks (EQ-5D-5L)
Change in Lequesne's Algofunctional Index Baseline-Week 24 Change from baseline in Lequesne's Algofunctional Index at 6, 12, 18 and 24 weeks.
Rescue medication usage Week 6-Week 24 Rescue medication usage assessed at 6, 12, 18 and 24 weeks.
Overall response rate according to OMERACT (Outcome Measures in Rheumatology)-OARSI (Osteoarthritis Research Society International) criteria Week 6-Week 24 Overall response rate according to OMERACT-OARSI criteria at 6, 12, 18 and 24 weeks (this is a statistical analysis)
Trial Locations
- Locations (31)
Ospedale San Pietro - FATEBENEFRATELLI
🇮🇹Roma, Italy
Klinische Forschung Berlin-Mitte GmbH
🇩🇪Berlin, Germany
NZOZ VITAMED Gałaj i Cichomski Sp. j.
🇵🇱Bydgoszcz, Poland
Istituto Ortopedico Gaetano Pini
🇮🇹Milano, Italy
Rheumazentrum Prof. Dr. med. Gunther Neeck
🇩🇪Bad Doberan, Germany
DGS Schmerzzentrum Eichstätt
🇩🇪Eichstätt, Germany
AmBeNet GmbHDas Ambulante BehandlungsNetz
🇩🇪Leipzig, Germany
Fisiatria Policlinico di Napoli
🇮🇹Napoli, Italy
ETG Lublin
🇵🇱Lublin, Poland
ETG Warszawa
🇵🇱Warszawa, Poland
ETG Zamość
🇵🇱Zamość, Poland
Wasilczyk Medical Clinic Indywidualna Praktyka Lekarska Cezary Wasilczyk
🇵🇱Warszawa, Poland
ETG Łódź
🇵🇱Łódź, Poland
Klinika Zdrowej Kości
🇵🇱Łódź, Poland
Lubelskie Centrum Diagnostyczne
🇵🇱Świdnik, Poland
SOLB - Zbigniew Zegota
🇵🇱Ostróda, Poland
Europejskie Centrum Leczenia Chorób Cywilizacyjnych
🇵🇱Warszawa, Poland
CHU Centre Ville (Brull) - Bone Metabolism Unit
🇧🇪Liège, Belgium
DEEK University
🇭🇺Debrecen, Hungary
Revita Rendelő
🇭🇺Budapest, Hungary
Semmelweis Egyetem - Ortopediai Klinika
🇭🇺Budapest, Hungary
Swan Med SMO
🇭🇺Létavértes, Hungary
Szent Margit Rendelőintézet
🇭🇺Budapest, Hungary
MEDIDEA Egeszsegugyi es Szolgaltato Beteti Tarsasag
🇭🇺Kiskunfélegyháza, Hungary
ETG Chełm
🇵🇱Chełm, Poland
ETG Siedlce
🇵🇱Siedlce, Poland
NZOZ Wilmed
🇵🇱Warszawa, Poland
Centrum Medyczne Lukamed
🇵🇱Chojnice, Poland
Centrum Kliniczno-Badawcze
🇵🇱Elbląg, Poland
RCMed
🇵🇱Sochaczew, Poland
Gdańskie Centrum Zdrowia
🇵🇱Gdańsk, Poland