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Knee OsteoarthritisAPROOVENCT03679208

sAfety PerfoRmance chitOsan osteOarthritis ViscosupplEmentation

A study testing Investigational device coded KIO014 in people with Knee Osteoarthritis, run by Kiomed Pharma.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 40 to 85 years
Conditions the study is for
Knee Osteoarthritis
What is being tested?
Investigational device coded KIO014
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
No sites listed yet
Study dates
15 Oct 2018to 15 Dec 2019
Phase
Interventional
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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

About this study

Official title: Safety and Performance of the Intra-articular Injection of Animal-free Chitosan Biomaterial (Viscosupplementation) in Patients With Symptomatic Knee Osteoarthritis: a Pre-market Study.

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.

Being tested
Investigational device coded KIO014, Durolane(r) as control device
Medical subject headings
Osteoarthritis, Knee

What participants receive

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

  • Investigational device coded KIO014Device

    Innovative chitosan-based biomaterial intended for intraarticular injection.

  • Durolane(r) as control deviceDevice

    Crosslinked hyaluronic acid-based biomaterial intended for intraarticular injection.

Study groups in NCT03679208
Study groupRoleWhat they receive
Stage 1 Safety cohortExperimentalTwo 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.
Receives: Device: Investigational device coded KIO014
Stage 2 Performance (test group)ExperimentalOne 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.
Receives: Device: Investigational device coded KIO014
Stage 2 Performance (control group)Active comparatorOne 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.
Receives: Device: Durolane(r) as control device

What is being measured

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

  1. Safety using 4-point numerical rating scale for local effects

    At each visit, the treatment knee is assessed for the occurrence of local effects (joint pain, effusion or swelling) using a 4-point numerical rating scale (NRS) graded 0-3 (none, mild, moderate or severe).

    Measured: All time points for up to 12 months

  2. Change in pain at 3 months versus pre-injection baseline using the 5-graded Likert self-administered WOMAC pain questionnaire (Stage 2 cohort only)

    The WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) is a self-administered questionnaire designed to assess pain, stiffness, and physical function through a series of 24 questions divided into 3 subscales. The WOMAC pain score consists of 5 questions. Each question is graded 0-4 on the 5-graded Likert scale (none, mild, moderate, severe or extreme) relating to how much pain the subject has experienced during the last 48 hours. The mean score is reported.

    Measured: 3 months

Secondary outcomes (5)

  1. Changes from baseline in total score, pain, stiffness, and physical functioning subscales of the treatment knee as measured using the 5-graded Likert WOMAC at the different time points over 6 months.

    The WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) is a self-administered questionnaire designed to assess pain, stiffness, and physical function through a series of 24 questions divided into 3 subscales. Each question is graded 0-4 on the 5-graded Likert scale (none, mild, moderate, severe or extreme) relating to how much pain, stiffness or daily physical activities the subject has experienced during the last 48 hours. The score of each dimension, namely pain, stiffness and physical function, is calculated by simply adding the score for each question using the 5-graded Likert scale from 0 to 4. For each dimension, the mean score is reported.

    Measured: 6 months

  2. Changes from baseline in subject's pain using an 11-point Numerical Rating Scale (NRS) at the different time points over 6 months.

    Pain at rest is evaluated using a self-administered 11-point numerical rating scale (NRS) from "no pain = 0" to "worst pain = 10". Subject's pain can be used as a criterion for evaluating the OMERACT-OARSI responders.

    Measured: 6 months

  3. Changes from baseline in subject's global assessment using an 11-point Numerical Rating Scale (NRS) at the different time points over 6 months.

    Subject's global assessment is evaluated using a self-administered 11-point numerical rating scale (NRS) from "very poor = 0" to "excellent = 10". Subject's global assessment can be used as a criterion for evaluating the OMERACT-OARSI responders.

    Measured: 6 months

  4. Response to treatment according to Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology (OMERACT) at the different time points over 6 months.

    The proportion of subjects meeting the OMERACT criteria for the response to treatment from the Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology (OMERACT).

    Measured: 6 months

  5. Treatment responders with >40% improvement in pre-injection pain (WOMAC Likert) at the different time points over 6 months.

    The proportion of subjects with a 40% improvement in pre-injection pain as evaluated by the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score using the 5-graded Likert scale from 0 to 4 (none, mild, moderate, severe or extreme) relating to how much pain the patient has experienced during the last 48 hours.

    Measured: 6 months

Timeline

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

  1. First posted20 Sep 2018
  2. Study start15 Oct 2018 (estimated)
  3. Primary completion15 May 2019 (estimated)
  4. Study completion15 Dec 2019 (estimated)

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03679208
Sponsor's protocol ID
KIO014-APROOVE
Acronym
APROOVE
Status last verified
Sep 2018
First submitted
9 Jul 2018
Last updated
21 Sep 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Investigational device coded KIO014 in people with Knee Osteoarthritis, run by Kiomed Pharma.

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 14 inclusion and 33 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: status not confirmed, as of the sponsor's last update on 21 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

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?

Safety using 4-point numerical rating scale for local effects (time frame: All time points for up to 12 months). The study lists 2 primary outcomes in all. 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 NCT03679208.

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 21 Sep 2018.

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