Evaluation of Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stem Cells (BP CC 001) in Cartilage Defect of the Knee Joint

The primary objective of this Phase I/IIa study is the **evaluation of the safety** of the investigational product BP CC 001, which consists of 10 x 10⁶ mesenchymal stem cells (MSC) derived from umbilical cord tissue, suspended in 1 ml of cell culture medium, and applied to a collagen support structure (Chondro-Gide®). This is clinically relevant as it aims to determine the safety profile of this novel cell therapy approach for treating cartilage defects in the knee joint, potentially offering a new therapeutic option for patients with this condition.

Secondary objectives include the evaluation of the **efficacy** of the investigational medicinal product. This aspect of the study seeks to assess the therapeutic potential and clinical benefits of BP CC 001 in improving cartilage repair and function in the affected knee joint.

The clinical trial involves participants diagnosed with a **cartilage defect of the knee joint**. The study population includes individuals of any gender, aged between 18 and 60 years. Participants are required to have a symptomatic grade III/IV cartilage defect or an osteochondral defect with a maximum depth of 3 mm. The defect size should be between 2 and 6 cm², located on the femoral condyles, patella, or trochlea. The general health status of participants is assessed with a BMI of less than 35 kg/m², and they must have a KOOS pain sub-score of ≤ 70 in the affected knee joint and > 80 in the contralateral knee joint, measured without analgesics within the last 24 hours. The trial includes both male and female subjects, and the population is considered vulnerable. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, including the requirement for written informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, and **controlled** study to evaluate the safety and efficacy of the investigational product BP CC 001, a suspension of stem cells derived from umbilical cord tissue, for the treatment of cartilage defects in the knee joint. The trial is structured in two phases, Phase I and Phase IIa, and aims to assess both safety and efficacy endpoints. The primary endpoint is the proportion of patients experiencing a serious adverse event within 24 months post-surgery. Secondary endpoints include the regeneration of damaged cartilage, changes in knee joint pain, quality of life, symptoms, stiffness, activities of daily life, and physical resilience during sporting activities, all measured at 12 and 24 months after surgery.

The trial is expected to commence recruitment on April 1, 2025, and conclude by April 1, 2028. Participants will be involved in the study for a duration of up to 24 months. The study will include several key visits: an initial **screening** visit to determine eligibility based on criteria such as age, cartilage defect characteristics, and overall health status; a baseline visit for pre-surgery assessments; and follow-up visits at 12 and 24 months post-surgery to evaluate the primary and secondary endpoints. The end-of-study visit will mark the completion of the participant's involvement in the trial.

Inclusion criteria require participants to be between 18 and 60 years of age, with a symptomatic grade III/IV cartilage defect or an osteochondral defect requiring treatment. Exclusion criteria are not specified in the provided data. Participants may be terminated early from the study if they experience severe adverse events or if they no longer meet the study's inclusion criteria. The investigational product is administered via **intraarticular use**, and the trial will adhere to rigorous safety and efficacy assessments throughout its duration.

The clinical trial involves the administration of the investigational product **BP CC 001**, which is a **suspension** containing stem cells derived from umbilical cord tissue. The active substance, **BP CC 001**, is classified as a structurally diverse substance used in cell therapy. The product is manufactured by BIONCART GMBH and is not formulated for pediatric use. The suspension is administered via **intraarticular use**, specifically targeting cartilage damage in the knee joint. The dosage consists of 10 x 10⁶ umbilical cord-derived mesenchymal stem cells (UC-MSC) in a 1 ml cell culture suspension, applied to a collagen support structure known as Chondro-Gide®.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on evaluating the safety and efficacy of the investigational product, BP CC 001, in the context of cartilage repair. Participant compliance with the treatment regimen will be monitored throughout the trial to ensure adherence to the dosing schedule and administration protocol. The trial does not include any additional pharmaceutical forms or routes of administration beyond those specified for BP CC 001.

Efficacy in this clinical trial will be assessed through a series of predefined endpoints. The primary endpoint focuses on the safety profile, specifically the proportion of patients experiencing a serious adverse event within 24 months post-surgery. Secondary endpoints are designed to evaluate the efficacy of the investigational product, BP CC 001, in regenerating damaged cartilage and improving knee function. These include the **MOCART score** to measure cartilage regeneration, and various subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS) to assess changes in knee joint pain, quality of life, symptoms and stiffness, activities of daily living, and physical resilience during sporting activities. These parameters will be measured at 12 and 24 months after surgery, compared to baseline values obtained before surgery. The trial will also document all adverse events, including adverse reactions and serious adverse events, within 24 months post-surgery, with severity assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V 5.0). The data collection and analysis will be conducted using validated scales and methodologies to ensure the reliability and accuracy of the efficacy assessments.