Clinical trial NCT05978180: Safety of Use and Efficacy of Pandora for Patients Suffering from Gonarthrosis (PANDORA2)
Official title: Prospective, Multicenter, Randomized, Parallel Groups Study Comparing the Safety and the Efficacy of the Administration of One Intra-articular Injection of 4.8 Ml (HO-1) or Three Intra-articular Injections of 2.2 Ml (HS-3) of Pandora Gel to One Intra-articular Injection of 2.5 Ml (SINOVIAL®ONE), in Symptomatic Gonarthrosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: Osteoarthritis
Viscosupplementation
Hyaluronic acid
Knee
Intra-articular injection
Tranexamic acid
Lead sponsor: Labrha
Sponsor class: INDUSTRY
Collaborators: name: Statitec
First posted: 2023-08-07
Enrollment: 252
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, controlled, single blind, randomized in parallel groups Clinical Investigation.

Subjects will receive one of three viscosupplementations depending on the randomization.

The study includes two periods :

* The first period (26 weeks) : prospective, multicenter, randomized in three parallel groups study, comparing the two forms of Pandora gel (HO-1 and HS-3) to SINOVIAL® ONE. The comparison between HO-1 and SINOVIAL® ONE is realized in single blind and the comparison between HS-3 and SINOVIAL® ONE is realized without masking.
* The second period (26 weeks) is an exploratory, prospective, multicenter phase comparing these same devices without masking.
Primary purpose: TREATMENT

Brief summary: The knee osteoarthritis is a frequent degenerative condition that mainly affects subjects over 60, population often weakened by numerous comorbidities and concomitant treatments, justifying the development of new therapies.

The viscosupplementation is a symptomatic treatment for knee osteoarthritis ; the objective of this intra-articular injection of hyaluronic acid is to reduce knee pain and improve mobility. In practice, there are two protocols to administer viscosupplementation : in a single injection or in three injections performed weekly.

The present clinical investigation has the objective to evaluate the safety and efficacy of use of Pandora, a hyaluronic acid associated with tranexamic acid, in a single injection (HO-1) or in three injections performed weekly (HS-3), compared to a referred and commercialized medical device.

Detailed description: This clinical investigation is a prospective, multicenter, randomized, parallel groups study of a class III Medical Device.

This study is designed to compare the safety of use and the efficacy of Pandora in its two forms : in a single injection (HO-1) or in three injections (HS-3) to a single intra-articular injection of 2.5 ml (SINOVIAL®ONE)

A descriptive analysis will be carried out to characterize the demographic data, the history of the disease and its treatments, the clinical and radiological data of the patients at inclusion.

The efficacy of Pandora will be demonstrated by describing the variation of WOMAC A1 score "walking pain" of target knee in repeated measures.

In total, 252 participants will be enrolled across 40 study centers in France and Monaco.

The total duration of subjects' participation is 12 months ; overall study duration including the enrollment period is expected to take approximately 24 months.

Eligibility criteria: Inclusion Criteria :

* Patient aged between 35 and 85 years.
* Body mass index (BMI) \< 35 kg.m2.
* Medial or lateral femoro-tibial knee osteoarthritis, diagnosed according to the American College of Rheumatology criteria, radiological stage 2 and 3 according to the Kellgren-Lawrence criteria modified by Felson on an X-ray, of the knee in extension, less than 6 months old.
* Knee osteoarthritis responsible for walking pain in the target knee, assessed between 4 and 8 inclusive on an 11 points numerical scale (0 = none to 10 = extreme).
* Unilateral or bilateral knee osteoarthritis if the walking pain in the contralateral knee is \< 3 based on 11 points numerical scale (0-10).
* Ambulatory patient able to walk 50 meters without a cane, crutch or walker.
* Patient giving his informed consent.
* Patient agreeing to follow-up study visits.
* Patient affiliated to the health social security system or beneficiary of such plan.
* Patient requiring viscosupplementation according to the investigator.

Exclusion Criteria :

* Patient presenting knee osteoarthritis without impingement joint space narrowing of the femoro-tibial compartment (modified Kellgren stage 0-1) or with complete impingement joint space narrowing on the knee weight-bearing radiograph in extension (modified Kellgren stage 4).
* Patient with bilateral symptomatic gonarthrosis with walking pain of contralateral knee \> 3.
* Patient with stage 4 patello-femoral osteoarthritis associated with femoro-tibial osteoarthritis.
* Patient with a flare of osteoarthritis of the target or contralateral knee.
* Patient who received viscosupplementation or Platelet Rich Plasma (PRP) injection, in the target knee, in the 6 months prior to inclusion.
* Patient who received an intra-articular injection of corticosteroids in the target knee in the 2 months prior to inclusion.
* Patients with a skin condition or a wound next to or near the injection site.
* Patients refusing to discontinue treatment with NSAIDs or cox-2 inhibitors during the follow-up period.
* Patient receiving treatment with level III analgesics (strong opioids).
* Patients receiving treatment with diacerhein, avocado and soy unsaponifiables, glucosamine or chondroitin initiated less than 2 months prior to inclusion.
* Patient with hypersensitivity to hyaluronic acid or tranexamic acid.
* Patient with a history of seizures.
* Patient who had arthroscopy of the target knee or major trauma to the target knee during the 3 months preceding inclusion.
* Patient scheduled to undergo surgery, for any cause, of the target knee or other joint of the lower limbs, planned within 6 months of inclusion, likely to interfere with follow-up or evaluation of the patient in the study.
* Patient with Fibromyalgia.
* Patient with an active neurological or vascular musculoskeletal disorder (such as rheumatoid arthritis, lupus, psoriatic arthritis, spondyloarthritis or any other autoimmune disease, Paget's disease, gout, coxopathy, tendinopathy of the lower limb, sciatic or crural radiculalgia) which, in the opinion of the investigator, would be likely to disrupt regular monitoring and/or interfere with the measurement of evaluated knee treatment efficacy.
* Patient with serious hemostasis disorders, venous or lymphatic stenosis of the lower limbs, history of thromboembolic disease - phlebitis or pulmonary embolism - or a high risk of thromboembolism.
* Patients with renal insufficiency.
* Patients with all evolving general condition as cardiac, digestive, endocrine, haematological or broncho-pulmonary which, in the opinion of the investigator, would be likely to disrupt regular monitoring and/or interfere with the measurement of evaluated knee treatment efficacy.
* Breastfeeding patient, pregnant or wishing to be during the 12 months of the study.
* Patients of childbearing age, sexually active without contraception.
* Patients unable to give personal consent.
* Patients participating or having participated in interventional research and whose follow-up ended within 2 months prior to inclusion.

Primary outcomes:
measure: To evaluate the efficacy of the two medical devices containing Pandora gel, HO-1 and HS-3, on walking pain in the target knee, compared to the SINOVIAL® ONE.
timeFrame: 6 months
Secondary outcomes:
measure: To evaluate the efficacy of viscosupplementation by HO-1 and HS-3 on walking pain of the target knee between day 1 and week 12.
timeFrame: 3 months
measure: To evaluate the efficacy of viscosupplementation by HO-1 and HS-3 on the pain of the target knee at weeks 4, 12 and 26 and week 12 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To evaluate the efficacy of viscosupplementation by HO-1 and HS-3 on the function of target knee at weeks 4, 12, 26 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To evaluate the efficacy of viscosupplémentation by HO-1 and HS-3 on the analgesic drug consumption at weeks 4, 12, 26 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To determine the number (and percentage) of patients "OMERACT-OARSI responsive" at weeks 4,12,26 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To determine the number (and percentage) of "highly responsive" patients at weeks 4, 12 and 26 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To determine the number (and percentage) of patients in whom target knee pain is considered acceptable according to the PASS criterion at weeks 4,12 and 26 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To determine the number (and percentage) of patients in whom the decrease of the target knee pain is considered important (MCII criterion) at weeks 4,12 and 26 as well as week 52 for patients who didn't require an injection at week 26.
timeFrame: 12 months
measure: To determine the number (and percentage) of patients requiring a new injection at S26.
timeFrame: 6 months
measure: To evaluate, at S52, the efficacy of the additional injection of HO-1 at S26 on pain and function of the target knee.
timeFrame: 12 months
measure: To evaluate, at S52, the benefit of the additional injection of HO-1 at S26 on analgesic drug consumption.
timeFrame: 12 months
measure: To measure the self-reported treatment efficacy by the patient at weeks 4, 12, 26 and 52.
timeFrame: 12 months
measure: To evaluate the local tolerability (at the target knee), after each injection of HO-1 and HS-3, compared to SINOVIAL® ONE.
timeFrame: 1 month
measure: To evaluate the global tolerability of HO-1 and HS-3 throughout the follow-up between day 1 and week 52 in comparison with SINOVIAL® ONE.
timeFrame: 12 months
measure: To assess patient's satisfaction regarding tolerability of HO-1 and HS-3 treatment between day 1 and week 4, compared to SINOVIAL® ONE.
timeFrame: 1 month
measure: To assess patient's satisfaction regarding the tolerability of HO-1 treatment at week 27 for patients who received an injection at week 26.
timeFrame: 6 months and one week (=27 weeks)
Other outcomes:
Locations:
city: Annecy
country: France
facility: Cabinet de Rhumatologie
city: Arnas
country: France
facility: Centre de Chirurgie Orthopédique du Beaujolais
city: Arnas
country: France
facility: Centre de Médecine du Sport du Beaujolais
city: Bagnols-sur-Cèze
country: France
facility: Cabinet de Rhumatologie
city: Belfort
country: France
facility: Cabinet de Rhumatologie La Savoureuse
city: Belfort
country: France
facility: Hôpital Nord Franche Comté
city: Besançon
country: France
facility: Cabinet de Rhumatologie de Palente
city: Bourgoin-Jallieu
country: France
facility: Centre de Rhumatologie Nord Isère
city: Castelnaudary
country: France
facility: Cabinet de Rhumatologie
city: Gap
country: France
facility: Polyclinique des Alpes du Sud
city: Gourdon
country: France
facility: Cabinet de Rhumatologie
city: La Ciotat
country: France
facility: Centre Médical Dulac
city: Lyon
country: France
facility: Cabinet Médical Tilsitt
city: Lyon
country: France
facility: Centre Orthopédique Santy
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Clinique Saint Charles
city: Mantes-la-Jolie
country: France
facility: Centre Médico-Social du Lac
city: Marseille
country: France
facility: Cabinet Médical Borely Mermoz
city: Montpellier
country: France
facility: Cabinet de Rhumatologie
city: Montpellier
country: France
facility: Centre Médical Saint Roch
city: Montélimar
country: France
facility: Cabinet Médical
city: Montélimar
country: France
facility: Groupe Médical Adhémar
city: Mulhouse
country: France
facility: Cabinet Médical Pluridisciplinaire Wallach
city: Mâcon
country: France
facility: Cabinet de Rhumatologie
city: Nîmes
country: France
facility: Cabinet de Rhumatologie
city: Ploemeur
country: France
facility: Clinique du Ter
city: Puyricard
country: France
facility: Cabinet Médical
city: Roanne
country: France
facility: Cabinet de Rhumatologie
city: Saint-Paul-lès-Dax
country: France
facility: Cabinet Médical
city: Strasbourg
country: France
facility: Groupe Médical Spécialisé - Le Premium
city: Vesoul
country: France
facility: Groupe Hospitalier de la Haute Saône - Hôpital de Vesoul
city: Villeurbanne
country: France
facility: Cabinet de Rhumatologie
city: Viry-Châtillon
country: France
facility: Cabinet de Rhumatologie
city: Vourles
country: France
facility: Pôle de santé des Sept Chemins
city: Monaco
country: Monaco
facility: IM2S
Study officials:
affiliation: Labrha
name: Patrick Sac-Epee
role: STUDY_DIRECTOR
affiliation: Hôpital Nord Franche-Comté, HNFC
name: Jean-Charles Balblanc, Dr
role: PRINCIPAL_INVESTIGATOR
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citation: Li J, Liu R, Rai S, Ze R, Tang X, Hong P. Intra-articular vs. intravenous administration: a meta-analysis of tranexamic acid in primary total knee arthroplasty. J Orthop Surg Res. 2020 Dec 2;15(1):581. doi: 10.1186/s13018-020-02119-1.
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