sAfety PerfoRmance chitOsan osteOarthritis ViscosupplEmentation (APROOVE)

KiOmed Pharma

Status: Unknown

Conditions: Knee Osteoarthritis

Treatments: Device: Investigational device coded KIO014; Device: Durolane(r) as control device

Study type: Interventional

Funder types: Industry

Identifiers

NCT03679208

KIO014-APROOVE

Details and patient eligibility

About

KIO014 is an innovative chitosan-based biomaterial intended for synovial fluid viscosupplementation indicated for the symptomatic treatment of knee osteoarthritis (OA). The study KIO014-APROOVE is aimed to evaluate the safety and performance of KIO014 in patients with symptomatic knee OA. A total of 100 patients will be enrolled. The study is divided in two stages. The Stage 1 cohort is the safety cohort where 10 patients will be enrolled. Stage 1 patients receiving two injections of KIO014 at day 0 and at month 3, and will be followed for 12 months post initial injection. The Stage 2 cohort is the performance cohort for 90 patients, and this stage will be randomized controlled and single-blind for the patient. In stage 2, 60 patients will receive an intra-articular injection of KIO014 (test group) and 30 patients will receive an intra-articular injection of Durolane® (control group). Patients will be followed for 6 months.

Enrollment: 100 estimated patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female with age ≥ 40 years and ≤ 85 years except in Stage 1 cohort where age is limited to ≤ 70 years.

• Body mass index (BMI) ≤ 35 kg/m².

• Uni- or bilateral femorotibial knee OA associated or not with femoropatellar knee OA.

• Primary knee osteoarthritis responding to the clinical and radiological criteria of the American College of Rheumatology (ACR)

• Radiological Kellgren and Lawrence (K&L) grade II to III from a standing knee radiograph taken less than 6 months previously.

• Symptomatic pain at least 6 months in the treatment knee not or poorly responding to first line non-opioid analgesics and non-steroidal anti-inflammatory drug in oral uptake.

• Pain criteria assessed prior to injection at visit 1 after mandatory 48-hour wash-out:

  • Treatment knee: 7-17 points of the 5-graded Likert WOMAC pain score and at least 2 points on the WOMAC pain subscore A1 in the most affected knee.
  • Non-treatment knee: not more than 6 points of the 5-graded Likert WOMAC pain score in the contralateral knee.

• Fully ambulatory patient for functional evaluation

• Willing NOT to take any pain medication for 48 hours prior to study visit.

• For female NOT surgically sterile (tubal ligation or hysterectomy) or NOT postmenopausal for at least one year, must have an effective contraception (pill, patch, ring, diaphragm, implant and intrauterine device).

• Able to understand and follow the instructions of the study.

• Having signed a written informed consent.

Exclusion criteria

• Related to the OA pathology and related symptoms:

  • Radiological K&L grade 0, I or IV from a standing knee radiograph taken less than 6 months previously.
  • Exclusively patellofemoral osteoarthritis where the symptoms, including pain, are principally of patellofemoral origin (Patellar syndrome).
  • Chondromatosis or villonodular synovitis of the knee.
  • Clinically-apparent knee effusion, inflammation or flare-up of the knee or abnormal synovial fluid macroscopy or volume upon arthrocentesis on the day of injection.
  • History of injury to the treatment knee during the 6 months before inclusion or recent trauma (<1 month) of the knee responsible of pain that is not directly related to OA symptoms.
  • Significant clinically-assessed or radiographic varus or valgus deformation of the selected knee at the judgment of the investigator.
  • Inflammatory disease.
  • Pathologies interfering with the evaluation of OA pain for the knee to be treated.

• Related to treatments:

  • Contraindications: hypersensitivity or allergy to the product components of KIO014, including chitosan, sorbitol and/or other mushroom-derived products, or to hyaluronic acid-based products.
  • Corticosteroids or Plasma Rich Platelet (PRP) or cell-based therapy injection in the treatment knee in the last 3 months before injection.
  • Hyaluronic acid injection in the treatment knee in the last 6 months before injection.
  • Arthroscopy and surgery in the treatment knee in the last 6 months before injection.
  • Oral corticotherapy ≥5 mg/day (in prednisone equivalent) in the last 3 months before injection.
  • Change in the dosage regimen of symptomatic slow-acting drugs (SYSAD) or dietary supplement in the last 3 months before injection.
  • Change in physiotherapy of the treatment knee in the last 3 months.
  • Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the treatment knee.
  • Anticipated need for any forbidden OA treatments during the trial except for rescue treatment as defined in the study protocol.
  • Anticoagulants: coumarin-based compounds or heparin.

• Related to associated diseases:

  • Any Investigator-assessed clinically significant condition that may represent a substantial risk to the patient or may have an impact on the study assessments.
  • History of recurrent bacterial infection, defined as at least 3 major infections resulting in hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years or history of synovial infection or infections or skin diseases in the area of the injection site.
  • History of symptomatic hip OA
  • History of autoimmune disease.
  • Severe, ongoing and uncontrolled diseases, or other major disease, or other severe uncontrolled conditions.
  • Subject addicted to alcohol or drugs or ongoing or recently recovered depression or psychiatric disorders or any other disorder and/or that may pose a health risk to the subject in the study and/or may have an impact on the study assessments.
  • Severe alteration of mobility preventing any functional evaluation.
  • High risk of hemorrhage.

• Related to patients:

  • Participation in a therapeutic clinical trial in the last 3 months before injection.
  • Patient under guardianship or judicial protection.
  • Pregnancy, breastfeeding, planned conception, or premenopausal women without effective contraception, tubal ligation or hysterectomy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 3 patient groups

Stage 1 Safety cohort

Experimental group

Description:

Two injections of the investigational device (KIO014) at 3-month interval in 10 patients and 12-month follow-up to establish long-term safety as primary endpoint.

Treatment:

Device: Investigational device coded KIO014

Stage 2 Performance (test group)

Experimental group

Description:

One injection of the investigational device (KIO014) in 60 patients to evaluate the reduction in pain at 3 months as primary endpoint. Additional follow-up at 6 months.

Treatment:

Device: Investigational device coded KIO014

Stage 2 Performance (control group)

Active Comparator group

Description:

One injection of the control device (Durolane(r)) in 30 patients to evaluate the reduction in pain at 3 months as control endpoint. Additional follow-up at 6 months.

Treatment:

Device: Durolane(r) as control device