Clinical trial NCT04358120: A Multicentre Clinical Investigation to Assess Efficacy and Safety of Intra-articular Injections of Hyaluronic Acid Combined With Chondroitin Sulfate in Knee Osteoarthritis
Official title: A Multicentre Clinical Investigation to Assess Efficacy and Safety of Intra-articular Injections of a New Viscosupplement Based on Hyaluronic Acid Combined With Chondroitin Sulfate in Patients With Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteo Arthritis Knee
Keywords: Hyaluronic Acid
Chondroitin sulfate
Lead sponsor: Fidia Farmaceutici s.p.a.
Sponsor class: INDUSTRY
First posted: 2020-04-24
Enrollment: 74
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicentre, prospective, sponsor initiated clinical investigation that aims to evaluate safety and efficacy of Hyaluronic Acid Combined With Chondroitin Sulfate in symptomatic patients with OA of the knee.


Eligibility criteria: Inclusion Criteria:

* At Screening

  * Male or female between the ages of 40 and 80
  * Body Mass Index (BMI) ≤ 30;
  * Mean knee pain score at rest over the last 24 hours evaluated on VAS (0-100) ≥ 40. The most painful knee is considered the target knee;
  * OA of the Knee radiologically and clinically confirmed responding to criteria of American College of Rheumatology (ACR): pain of the knee and crepitus on active motion or morning stiffness less than 30 minutes or age \>50 years
  * Symptomatic knee pain for more than 6 months;
  * Radiological Kellgren and Lawrence grade II or III confirmed by an X-ray not older than 12 months;
  * Willing to discontinue any systemic analgesic/NSAID therapy, opioids, systemic corticosteroids, skeletal muscle relaxants, and any other medication that would interfere with the study assessments, except for the rescue medication, with no intention to resume them during the clinical investigation (see Appendix 5 for wash out period);
  * Patient able to comply with the instructions of the clinical investigation and to maintain a Rescue Medication Diary during the study;
  * Having signed the study informed consent.
* at Baseline

  * Patient does not have chondromatosis or villonodular synovitis of the knee evaluated by Ultrasound;
  * Patient has complied with the requirements for rescue medication (no more than 6 tablets or 3 grams of paracetamol per day up to 4 days per week and paracetamol discontinued 24 hours before first IA injection);
  * Mean knee pain score at rest over the last 24 hours evaluated on VAS (0 - 100) ≥ 40 (with a washout period for Paracetamol of 24 hours);
  * Patient has discontinued prior to Baseline the use of all prohibited medications in accordance with the washout period defined in Appendix 5;
  * Patient continues to meet all Screening inclusion/exclusion criteria at the Baseline visit.

Exclusion Criteria:

* Related to the OA pathology

  * Recent trauma (\< 1 month) of the target knee responsible for the symptomatic knee pain;
  * Articular disease resulting from articular dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, haemophilia, hemochromatosis;
  * Inflammatory or autoimmune diseases (e.g., rheumatoid arthritis, gout and infectious arthritis, acute calcium pyrophosphate arthritis);
  * Pathologies interfering with the evaluation of OA. Related to treatments
  * Corticosteroids injection in the target knee in the last 3 months before first intra-articular (IA) injection;
  * Hyaluronan injection in the target knee in the last 6 months before first IA injection;
  * Arthroscopy and surgery in the target knee in the last 3 months before first IA injection;
  * Oral corticosteroid therapy ≥ 5mg/day (in Prednisone equivalent) in the last 3 months before first IA injection;
  * OA treatments based on curcuma extract in the last 3 months before first IA injection;
  * Change in the dosage of symptomatic slow-acting drugs (SYSADOA) e.g., chondroitin, glucosamine, diacerein or avocado-soya unsaponifiables in the last 3 months before first IA injection;
  * Contraindications to 4% GAG: hypersensitivity to the product components;
  * Infections or skin diseases in the area of the injection site;
  * Change in the dosage of ongoing non-pharmacologic therapy for the lower extremities (including physical therapy) initiated in the month before first injection;
  * Anticoagulant (coumarinic compound) and heparin. Related to associated diseases
  * Severe diseases (e.g., liver or renal failure, lung/heart disease, tumour, HIV);
  * Severe alteration of mobility interfering with the functional evaluation;
  * High risk of haemorrhage;
  * Patient with known allergy to paracetamol;
  * Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee.

Related to study subjects

* Participation to a therapeutic clinical trial in the last 3 months before first injection;
* Pregnancy, breastfeeding, planned conception and premenopausal women without contraception, tubal ligation or hysterectomy

Primary outcomes:
measure: Change in pain score measured by Visual Analogue Scale (VAS)
timeFrame: at week 6, 14 and 26
Secondary outcomes:
measure: Change in Patient's Global Assessment
timeFrame: at weeks 6, 14 and 26
measure: Change from baseline in knee pain and function up to 26 weeks
timeFrame: at weeks 6, 14 and 26
measure: Change from baseline up to 26 weeks after first treatment on knee functional disability on Clinical Observer Global Assessment (COGA)
timeFrame: at weeks 6, 14 and 26
measure: Number of patients Responder to treatment
timeFrame: Weeks 6, 14 and 26
measure: Change from baseline in Synovitis at 6 weeks
timeFrame: at week 6
measure: Change from baseline in Synovial hypertrophy at 6 weeks
timeFrame: at week 6
measure: Change from baseline in knee Effusion at 6 weeks
timeFrame: at week 6
measure: Change from baseline in popliteal cyst at 6 weeks
timeFrame: at week 6
measure: Change in Synovial Power Doppler signal at week 6
timeFrame: at week 6
measure: Safety of the treatment. Number of patient with treatment related adverse events
timeFrame: through study completion
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Revmacentrum MUDr. Mostera,
city: Brno
country: Czechia
facility: Rheumatology, Polyclinic Lesná
city: Prague
country: Czechia
facility: Institute of rheumatology
city: Prague
country: Czechia
facility: University Hospital Motol, Department of Rheumatology of Children and Adults
city: Uherské Hradiště
country: Czechia
facility: Medical Plus, s.r.o
Study officials:
References: