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Knee OsteoarthritisPhase 3NCT03200288

A Study to Evaluate the Clinical Performance and Safety of an Intra-articular Hyaluronic Acid in Knee Osteoarthritis

A Phase 3 study testing HL-01: high and low molecular weight hyaluronic acid in people with Knee Osteoarthritis, run by IBSA Institut Biochimique SA at 31 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Knee Osteoarthritis
What is being tested?
HL-01: high and low molecular weight hyaluronic acid
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
692 participants
Where
31 sitesin 5 countries
Study dates
29 Jun 2017to 30 Oct 2018
Phase
Phase 3
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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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.
  • 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:
  • 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.
  • Topical anti-inflammatories and analgesics applied at the target knee in the past 48 hrs.
  • Viscosupplementation with hyaluronic acid or joint-lavage in the target knee in the past year.
  • 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.
  • 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.

Trial locations and contacts

31 sites in 5 countries.

31 sites in 5 countries

Poland17 sites

  • NZOZ VITAMED Gałaj i Cichomski Sp. j.

    Bydgoszcz

  • ETG Chełm

    Chełm

  • Centrum Medyczne Lukamed

    Chojnice

  • Centrum Kliniczno-Badawcze

    Elblag

  • Gdańskie Centrum Zdrowia

    Gdansk

  • ETG Łódź

    Lodz

  • Klinika Zdrowej Kości

    Lodz

  • ETG Lublin

    Lublin

  • SOLB - Zbigniew Zegota

    Ostróda

  • ETG Siedlce

    Siedlce

  • RCMed

    Sochaczew

  • Lubelskie Centrum Diagnostyczne

    Świdnik, 21-040

  • ETG Warszawa

    Warsaw

  • Europejskie Centrum Leczenia Chorób Cywilizacyjnych

    Warsaw

  • NZOZ Wilmed

    Warsaw

  • Wasilczyk Medical Clinic Indywidualna Praktyka Lekarska Cezary Wasilczyk

    Warsaw

  • ETG Zamość

    Zamość

Other trials in Poland

Hungary6 sites

  • Revita Rendelő

    Budapest

  • Semmelweis Egyetem - Ortopediai Klinika

    Budapest

  • Szent Margit Rendelőintézet

    Budapest

  • DEEK University

    Debrecen

  • MEDIDEA Egeszsegugyi es Szolgaltato Beteti Tarsasag

    Kiskunfélegyháza

  • Swan Med SMO

    Létavértes

Other trials in Hungary

Germany4 sites

  • Rheumazentrum Prof. Dr. med. Gunther Neeck

    Bad Doberan

  • Klinische Forschung Berlin-Mitte GmbH

    Berlin

  • DGS Schmerzzentrum Eichstätt

    Eichstätt

  • AmBeNet GmbHDas Ambulante BehandlungsNetz

    Leipzig

Other trials in Germany

Italy3 sites

  • Istituto Ortopedico Gaetano Pini

    Milan

  • Fisiatria Policlinico di Napoli

    Naples

  • Ospedale San Pietro - FATEBENEFRATELLI

    Roma

Other trials in Italy

Belgium1 site

  • CHU Centre Ville (Brull) - Bone Metabolism Unit

    Liège

Other trials in Belgium

About this study

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

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.

Being tested
HL-01: high and low molecular weight hyaluronic acid, Placebo
Medical subject headings
Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HL-01: high and low molecular weight hyaluronic acidDevice

    Also called Sinovial HL®

    2 ml intra-articular single injection

  • PlaceboDevice

    2 ml intra-articular single injection

Study groups in NCT03200288
Study groupRoleWhat they receive
HL-01ExperimentalSingle 2 ml intra-articular injection of HL-01 (solution of high and low molecular weight hyaluronic acid (HA))
Receives: Device: HL-01: high and low molecular weight hyaluronic acid
PlaceboPlacebo comparatorSingle 2 ml intra-articular injection of Placebo (physiological solution)
Receives: Device: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in VAS (Visual Analogue Scale) pain score

    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.

    Measured: Baseline-week 24

Secondary outcomes (5)

  1. Change in Lequesne's Algofunctional Index

    Change from baseline in Lequesne's Algofunctional Index at 6, 12, 18 and 24 weeks.

    Measured: Baseline-Week 24

  2. Change in global status assessed by subject (EQ-5D-5L EuroQol Group Health questionnaire)

    Change from baseline in global status assessed by subject at 6, 12, 18 and 24 weeks (EQ-5D-5L)

    Measured: Baseline-Week 24

  3. Change in global status assessed by physician

    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'

    Measured: Baseline -Week 24

  4. Overall response rate according to OMERACT (Outcome Measures in Rheumatology)-OARSI (Osteoarthritis Research Society International) criteria

    Overall response rate according to OMERACT-OARSI criteria at 6, 12, 18 and 24 weeks (this is a statistical analysis)

    Measured: Week 6-Week 24

  5. Rescue medication usage

    Rescue medication usage assessed at 6, 12, 18 and 24 weeks.

    Measured: Week 6-Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2017
  2. Study start29 Jun 2017
  3. Primary completion27 Jun 2018
  4. Study completion30 Oct 2018

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
692 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03200288
Sponsor's protocol ID
16EU-Hai13
Status last verified
Feb 2019
First submitted
21 Jun 2017
Last updated
16 Nov 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34462887

  • 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.

    PubMed 32954487

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing HL-01: high and low molecular weight hyaluronic acid in people with Knee Osteoarthritis, run by IBSA Institut Biochimique SA at 31 sites in 5 countries.

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 10 inclusion and 27 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 16 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Poland, Hungary, Germany, Italy, Belgium. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Change in VAS (Visual Analogue Scale) pain score (time frame: Baseline-week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03200288, which also lists 2 linked publications.

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 16 Nov 2021.

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