Treatment of patellofemoral osteoarthritis with nasal chondrocyte-based engineered cartilage implantation in a randomized, controlled, multi-center phase II clinical trial
Description: Background: Knee osteoarthritis (OA) is one of the most common causes for pain and disability with over 260 million people affected worldwide. Due to raising life expectancy and obesity estimations, a further increase is expected, leading to a tremendous socio-economic burden. Recent studies found that knee OA often starts in the patello-femoral compartment of the knee (PFOA) and is diagnosed in ~39% of people with knee pain aged above 30 years. Thus, PFOA and progression to full OA plays a crucial role in the reduction of quality of life of many people and in the raise of healthcare costs. Due to a lack of high-level evidence studies, there is still no consensus for treatment recommendation for isolated PFOA in clinical guidelines. Moreover, current therapeutic approaches are limited to pain management, alleviation of symptoms or finally total knee replacement, but no regenerative approach or disease-modifying treatment is available. Even though results published for joint replacement are generally satisfactory, 10-15% of the patients are dissatisfied and report complications including, amongst others, progression of OA in the tibiofemoral joint and aseptic loosening. Therefore, a treatment option to delay artificial joint replacement with its potential drawbacks is desired. Nasal chondrocyte tissue engineered cartilage (N-TEC) has already been successfully introduced by the main applicant in clinical studies for the treatment of focal cartilage lesions, resulting in a publication in The Lancet and in an EU-funded trial (BIOCHIP 6681103: Clinicaltrials.gov NCT02673905, manuscript in preparation). Moreover, recently published data from in vitro experiments, pre-clinical studies in sheep and two clinical OA cases indicate the capacity of N-TEC to survive in inflammatory settings typical of OA environments, contribute to the repair tissue and elicit an anti-inflammatory effect.Design: We propose a randomized, controlled, multi-center, parallel-group, superiority trial for the treatment of PFOA with N-TEC to (i) evaluate the efficacy in comparison to an active comparator (Platelet Rich Plasma (PRP) injections) based on patients’ self-assessed outcome scores (Knee Osteoarthritis Outcome Score (KOOS Pain), and (ii) verify tissue regeneration as the postulated mode of action and thus the disease-modifying properties of the graft, as previously indicated in animal studies (x-ray, MRI). Both arms will receive targeted, standardized and as similar as possible physiotherapy treatment.Sample size and outcomes: 75 patients with a symptomatic PFOA grade 1-3 (Iwano classification) and a self-assessed KOOS Pain lower than 60 will be enrolled and randomized (1:1) to either surgical treatment or active comparator. The primary endpoint will be KOOS Pain at 24 months to judge treatment success. Secondary endpoints will include amongst others change in KOOS Pain from Baseline to 24 months, KOOS subscales (symptoms, activity of daily living (ADL), sports, Quality of Life (QOL)), Kujala Anterior Knee Pain Scale, WOMAC score and EQ-5d assessment at 6, 12 and 24 months compared to baseline. Further secondary endpoints will be the number of subjects non-responding to treatment (i.e., improvement in KOOS Pain below 13 units on a scale of 0-100) to evaluate efficacy. Adverse events will be recorded during the full course of the trial to assess safety. Furthermore, the experimental group will be compared with registry data of prosthetic treatment in a matched pair analysis.Expected Impact: The proposed randomized and controlled trial could pave the way towards an unprecedented cartilage regeneration paradigm in the treatment of osteoarthritic settings.
Amount: CHF 2,665,000
Funding type: research
Funder scheme: Investigator Initiated Clinical Trials (IICT)
Start date: 2023-09-01
End date: 2028-08-31
Investigator: Martin, Ivan
Institution: University of Basel – BS
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 214562
OpenAlex ID: G5272648787