Clinical trial NCT03200288: A Study to Evaluate the Clinical Performance and Safety of an Intra-articular Hyaluronic Acid in Knee Osteoarthritis
Official title: A Phase 3,Randomized,Double-blind,Placebo-controlled Study to Evaluate the Clinical Performance and Safety of an Intra-articular Solution of High and Low Molecular Weight Hyaluronic Acid (HL-01) in the Treatment of Pain in Symptomatic Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Knee Osteoarthritis
Lead sponsor: IBSA Institut Biochimique SA
Sponsor class: INDUSTRY
First posted: 2017-06-27
Enrollment: 692
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Subjects with secondary (post-traumatic) knee OA of the target and non-target joints.
* Subjects with K-L radiological grade 4 knee OA.
* Subjects with a history of knee joint replacement/arthroplasty of the target knee.
* Subjects with a history of arthroscopy, osteotomy, or surgery of the target knee in the past 12 months.
* Subjects with any significant injury to the target knee in the last 6 months (as per Investigator judgment).
* Subjects with Body Mass Index (BMI) ≥32 kg/m2.
* 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:

  1. severe varus/valgus deformity (\>15°)
  2. predominantly patello-femoral pain/syndrome.
* Subjects with a history of symptomatic hip OA or other health condition i.e. associated with pain and interfering with adequate study endpoints evaluation.
* 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.
* Subjects with venous or lymphatic stasis in the relevant limb.
* 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.
* Subjects with a history of chronic or recurrent use of NSAIDs/analgesics/narcotics because of diseases different from OA of the target knee.
* 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.
* Subjects who currently use heparin or anti-vitamin K (e. g. crystalline warfarin) anticoagulant therapy.
* Subjects with the presence of infection, skin diseases, other disease or trauma in the area of the injection site or joint.
* Subjects with a known history or suspected allergy or hypersensitivity to hyaluronic acid or to hyaluronate preparations.
* Subjects with a known history or suspected allergy or hypersensitivity to acetaminophen.
* Subjects with any major surgery scheduled in the next 6 months.
* Subjects who have participated in a clinical study / investigation in the last 3 months.
* Pregnant or lactating women and women of childbearing potential not willing to use adequate contraception.

Primary outcomes:
measure: Change in VAS (Visual Analogue Scale) pain score
timeFrame: Baseline-week 24
Secondary outcomes:
measure: Change in Lequesne's Algofunctional Index
timeFrame: Baseline-Week 24
measure: Change in global status assessed by subject (EQ-5D-5L EuroQol Group Health questionnaire)
timeFrame: Baseline-Week 24
measure: Change in global status assessed by physician
timeFrame: Baseline -Week 24
measure: Overall response rate according to OMERACT (Outcome Measures in Rheumatology)-OARSI (Osteoarthritis Research Society International) criteria
timeFrame: Week 6-Week 24
measure: Rescue medication usage
timeFrame: Week 6-Week 24
Other outcomes:
measure: Adverse Events
timeFrame: Screening -Week 24
measure: Level of treatment satisfaction
timeFrame: Baseline-Week 6
Locations:
city: Liège
country: Belgium
facility: CHU Centre Ville (Brull) - Bone Metabolism Unit
city: Bad Doberan
country: Germany
facility: Rheumazentrum Prof. Dr. med. Gunther Neeck
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Mitte GmbH
city: Eichstätt
country: Germany
facility: DGS Schmerzzentrum Eichstätt
city: Leipzig
country: Germany
facility: AmBeNet GmbHDas Ambulante BehandlungsNetz
city: Budapest
country: Hungary
facility: Revita Rendelő
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - Ortopediai Klinika
city: Budapest
country: Hungary
facility: Szent Margit Rendelőintézet
city: Debrecen
country: Hungary
facility: DEEK University
city: Kiskunfélegyháza
country: Hungary
facility: MEDIDEA Egeszsegugyi es Szolgaltato Beteti Tarsasag
city: Létavértes
country: Hungary
facility: Swan Med SMO
city: Milano
country: Italy
facility: Istituto Ortopedico Gaetano Pini
city: Napoli
country: Italy
facility: Fisiatria Policlinico di Napoli
city: Roma
country: Italy
facility: Ospedale San Pietro - FATEBENEFRATELLI
city: Bydgoszcz
country: Poland
facility: NZOZ VITAMED Gałaj i Cichomski Sp. j.
city: Chełm
country: Poland
facility: ETG Chełm
city: Chojnice
country: Poland
facility: Centrum Medyczne Lukamed
city: Elbląg
country: Poland
facility: Centrum Kliniczno-Badawcze
city: Gdańsk
country: Poland
facility: Gdańskie Centrum Zdrowia
city: Lublin
country: Poland
facility: ETG Lublin
city: Ostróda
country: Poland
facility: SOLB - Zbigniew Zegota
city: Siedlce
country: Poland
facility: ETG Siedlce
city: Sochaczew
country: Poland
facility: RCMed
city: Warszawa
country: Poland
facility: ETG Warszawa
city: Warszawa
country: Poland
facility: Europejskie Centrum Leczenia Chorób Cywilizacyjnych
city: Warszawa
country: Poland
facility: NZOZ Wilmed
city: Warszawa
country: Poland
facility: Wasilczyk Medical Clinic Indywidualna Praktyka Lekarska Cezary Wasilczyk
city: Zamość
country: Poland
facility: ETG Zamość
city: Łódź
country: Poland
facility: ETG Łódź
city: Łódź
country: Poland
facility: Klinika Zdrowej Kości
city: Świdnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne
Study officials:
References:
citation: Migliore A, Blicharski T, Plebanski R, Zegota Z, Gyula G, Rannou F, Reginster JY. Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial. Rheumatol Ther. 2021 Dec;8(4):1617-1636. doi: 10.1007/s40744-021-00363-3. Epub 2021 Aug 30.
citation: Bruyere O, Dardenne N, Donneau AF, Reginster JY. Responder Profile to Pharmaceutical-Grade Chondroitin Sulfate: An Analysis of the CONCEPT Trial. Adv Ther. 2020 Nov;37(11):4641-4648. doi: 10.1007/s12325-020-01484-x. Epub 2020 Sep 21.