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

November 15, 2021 updated by: IBSA Institut Biochimique SA

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
692

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Liège, Belgium
        • CHU Centre Ville (Brull) - Bone Metabolism Unit
  • Germany
      • Bad Doberan, Germany
        • Rheumazentrum Prof. Dr. med. Gunther Neeck
      • Berlin, Germany
        • Klinische Forschung Berlin-Mitte GmbH
      • Eichstätt, Germany
        • DGS Schmerzzentrum Eichstätt
      • Leipzig, Germany
        • AmBeNet GmbHDas Ambulante BehandlungsNetz
  • Hungary
      • Budapest, Hungary
        • Revita Rendelo
      • Budapest, Hungary
        • Semmelweis Egyetem - Ortopediai Klinika
      • Budapest, Hungary
        • Szent Margit Rendelointézet
      • Debrecen, Hungary
        • DEEK University
      • Kiskunfélegyháza, Hungary
        • MEDIDEA Egeszsegugyi es Szolgaltato Beteti Tarsasag
      • Létavértes, Hungary
        • Swan Med SMO
  • Italy
      • Milano, Italy
        • Istituto Ortopedico Gaetano Pini
      • Napoli, Italy
        • Fisiatria Policlinico di Napoli
      • Roma, Italy
        • Ospedale San Pietro - FATEBENEFRATELLI
  • Poland
      • Bydgoszcz, Poland
        • NZOZ VITAMED Gałaj i Cichomski Sp. j.
      • Chełm, Poland
        • ETG Chełm
      • Chojnice, Poland
        • Centrum Medyczne Lukamed
      • Elbląg, Poland
        • Centrum Kliniczno-Badawcze
      • Gdańsk, Poland
        • Gdanskie Centrum Zdrowia
      • Lublin, Poland
        • ETG Lublin
      • Ostróda, Poland
        • SOLB - Zbigniew Zegota
      • Siedlce, Poland
        • ETG Siedlce
      • Sochaczew, Poland
        • RCMed
      • Warszawa, Poland
        • ETG Warszawa
      • Warszawa, Poland
        • Europejskie Centrum leczenia Chorob Cywilizacyjnych
      • Warszawa, Poland
        • NZOZ Wilmed
      • Warszawa, Poland
        • Wasilczyk Medical Clinic Indywidualna Praktyka Lekarska Cezary Wasilczyk
      • Zamość, Poland
        • ETG Zamosc
      • Łódź, Poland
        • ETG Łódz
      • Łódź, Poland
        • Klinika Zdrowej Kości
      • Świdnik, Poland, 21-040
        • Lubelskie Centrum Diagnostyczne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: HL-01
Single 2 ml intra-articular injection of HL-01 (solution of high and low molecular weight hyaluronic acid (HA))
Device: HL-01: high and low molecular weight hyaluronic acid
2 ml intra-articular single injection
Other Names:
  • Sinovial HL®
Placebo Comparator: Placebo
Single 2 ml intra-articular injection of Placebo (physiological solution)
Device: Placebo
2 ml intra-articular single injection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in VAS (Visual Analogue Scale) pain score
Time Frame: 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.
Baseline-week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Lequesne's Algofunctional Index
Time Frame: Baseline-Week 24
Change from baseline in Lequesne's Algofunctional Index at 6, 12, 18 and 24 weeks.
Baseline-Week 24
Change in global status assessed by subject (EQ-5D-5L EuroQol Group Health questionnaire)
Time Frame: Baseline-Week 24
Change from baseline in global status assessed by subject at 6, 12, 18 and 24 weeks (EQ-5D-5L)
Baseline-Week 24
Change in global status assessed by physician
Time Frame: 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'
Baseline -Week 24
Overall response rate according to OMERACT (Outcome Measures in Rheumatology)-OARSI (Osteoarthritis Research Society International) criteria
Time Frame: Week 6-Week 24
Overall response rate according to OMERACT-OARSI criteria at 6, 12, 18 and 24 weeks (this is a statistical analysis)
Week 6-Week 24
Rescue medication usage
Time Frame: Week 6-Week 24
Rescue medication usage assessed at 6, 12, 18 and 24 weeks.
Week 6-Week 24

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: Screening -Week 24
Incidence and frequency of AEs (adverse events)
Screening -Week 24
Level of treatment satisfaction
Time Frame: Baseline-Week 6
Level of treatment satisfaction - assessed by subject at baseline (within 15 minutes after the i. a. injection), in 24 hours (+/- 1 hour) after the injection, at week 1 and week 6
Baseline-Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IBSA Institut Biochimique SA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 29, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 27, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 23, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 16, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16EU-Hai13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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