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

Knee Osteoarthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03200288
• Other study ID #: 16EU-Hai13
• Status: Completed
• Phase: Phase 3
• Start date: June 29, 2017
• Est. completion date: October 30, 2018

Study information

• Verified date: February 2019
• Source: IBSA Institut Biochimique SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 692
• Est. completion date: October 30, 2018
• Est. primary completion date: June 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Device:
• HL-01: high and low molecular weight hyaluronic acid
2 ml intra-articular single injection
• Placebo
2 ml intra-articular single injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
IBSA Institut Biochimique SA

Countries where clinical trial is conducted

Belgium,  Germany,  Hungary,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events	Incidence and frequency of AEs (adverse events)	Screening -Week 24
Other	Level of treatment satisfaction	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
Primary	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.	Baseline-week 24
Secondary	Change in Lequesne's Algofunctional Index	Change from baseline in Lequesne's Algofunctional Index at 6, 12, 18 and 24 weeks.	Baseline-Week 24
Secondary	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)	Baseline-Week 24
Secondary	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'	Baseline -Week 24
Secondary	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)	Week 6-Week 24
Secondary	Rescue medication usage	Rescue medication usage assessed at 6, 12, 18 and 24 weeks.	Week 6-Week 24