Evaluation of Intra-Discal Allogeneic Bone Marrow Stromal Mesenchymal Cell Therapy in Lumbar Degenerative Disc Disease-Related Chronic Low Back Pain

The primary objective of this study is to assess the efficacy of **intradiscal injection** of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) in reducing chronic low back pain due to lumbar **degenerative disc disease** (DDD). This is evaluated using the visual analog scale (VAS) and the Oswestry Disability Index (ODI) after 12 months of treatment. A responder is defined as a patient with at least a 20% improvement and a 20 mm decrease in VAS for pain or a 20% improvement in ODI between baseline and month 12. Additionally, the study aims to evaluate the efficacy of this treatment in increasing disc fluid content, as measured by quantitative Magnetic Resonance Imaging (MRI), between baseline and month 12. These objectives are clinically relevant as they address the potential of BM-MSCs to provide a therapeutic option for patients with chronic low back pain unresponsive to conventional therapy, potentially improving pain management and functional outcomes.

Secondary objectives include: - Evaluating the efficacy of intradiscal injection of allogeneic BM-MSCs using VAS and ODI after 3, 6, and 24 months, defining responders as those with at least a 20% improvement in VAS or ODI compared to baseline. - Assessing the efficacy of allogeneic stem cell treatments for DDD on VAS modification between baseline and 3, 6, 12, and 24 months. - Evaluating changes in disability (ODI) and quality of life (SF-36 scores) between baseline and 3, 6, 12, and 24 months. - Evaluating modification of the affected disc by quantitative MRI signal measurements in T2 and T1rho weighted images between baseline, 6, 12, and 24 months. - Assessing changes in employment and work status between baseline and months 12 and 24. - Assessing safety and tolerability, measured by the nature and severity of adverse events, including procedure-related events such as infections, bleedings, nerve irritations, and injuries. - Evaluating the consumption of medications for pain relief, including type and dose of analgesics. - Assessing the immune response associated with allogeneic cell injection, including quantification of anti-HLA. - Assessing the safety of local MSC injection on the systemic immune system. - Evaluating medical and non-medical costs.

The clinical trial focuses on participants diagnosed with **Degenerative Disc Disease** (DDD), specifically targeting individuals experiencing chronic low back pain. The study population includes both male and female subjects, aged between 18 and 60 years, who have not responded to conservative therapy for at least three months. Participants are required to have a Pfirrmann's score of 4 to 7 at one level, with the possibility of a second adjacent level having a score of 1 to 4. The trial does not involve a vulnerable population. Lifestyle considerations include a washout period for NSAIDs of at least two days and for painkillers of at least 24 hours before screening. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy of intradiscal injection of allogeneic bone marrow stromal mesenchymal cells (BM-MSCs) in patients with chronic low back pain due to lumbar **degenerative disc disease** (DDD) unresponsive to conventional therapy. The trial is structured as a phase 2/3 study and aims to compare the therapeutic effects of BM-MSCs with sham-treated controls. The primary objectives are to assess pain reduction and functional improvement over a 12-month period, using the visual analog scale (VAS) and the Oswestry Disability Index (ODI), as well as to evaluate changes in disc fluid content through quantitative Magnetic Resonance Imaging (MRI).

The trial is expected to span from February 2019 to May 2026, with participant involvement lasting approximately 12 months. The study includes several key visits: an initial screening visit to confirm eligibility, baseline assessments, and follow-up visits at 12 and 24 months to monitor progress and collect data on primary and secondary endpoints. The inclusion criteria require participants to be aged between 18 and 60 years, with symptomatic chronic low back pain unresponsive to conservative therapy for at least three months, and a specific grading of DDD. Exclusion criteria are not specified in the provided data.

Participants will be randomly assigned to receive either the BM-MSC therapy or a sham treatment, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the trial. The primary endpoints focus on clinical response, defined as a significant reduction in pain and improvement in functional status, as well as an increase in disc fluid content. Secondary endpoints include assessments of disability, quality of life, pain medication usage, and safety outcomes.

Conditions that may lead to early termination from the study include adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial is not classified as low intervention, indicating a more intensive monitoring and data collection process. The investigational product, MSV Allogenic bone marrow stromal mesenchymal cells, is administered as a suspension for injection via intradiscal use, with a maximum daily dose of 2 ml. The study is conducted under the sponsorship of the University Hospital of Montpellier.

The clinical trial involves the administration of **MSV Allogenic bone marrow stromal mesenchymal cells**, a **suspension for injection**. This experimental medication is designed for **intradiscal use** and is classified as a somatic cell therapy. The active substance, identified as MSV/AS, originates from a structurally diverse substance used in cell therapy. The maximum daily and total dose is 2 ml, administered once during the treatment period, which spans a maximum of one day. The formulation is not specifically designed for pediatric use. The product is developed and provided by the University Hospital of Montpellier.

In addition to the experimental treatment, the study includes a comparator group receiving sham treatment. This group serves as a control to evaluate the efficacy of the MSV Allogenic bone marrow stromal mesenchymal cells in reducing chronic low back pain due to lumbar degenerative disc disease. The sham treatment is designed to mimic the procedure without delivering the active therapeutic agent, ensuring the study remains double-blind. Participant compliance with the treatment protocol is monitored throughout the trial to ensure adherence to the dosing schedule and to maintain the integrity of the study results.

The efficacy of the clinical trial will be assessed through two co-primary objectives. The first objective is to evaluate the efficacy of intradiscal injection of allogeneic bone marrow stromal mesenchymal cells (BM-MSCs) in reducing chronic low back pain due to lumbar degenerative disc disease (DDD). This will be measured using the Visual Analog Scale (VAS) for pain and the Oswestry Disability Index (ODI) for functional status. A responder is defined as a patient with an improvement of at least 20% and 20 mm on the VAS for pain, or a 20% improvement on the ODI, between baseline and month 12. The second objective is to assess the efficacy of the treatment in increasing disc fluid content, which will be measured by quantitative Magnetic Resonance Imaging (MRI) between baseline and month 12.

Primary endpoints include clinical response, defined as pain relief of at least 20% and a 20 mm decrease on the VAS scale, or a 20% improvement in the ODI at month 12 compared to baseline. The fluid content of the discs will be determined from T2-weighted sagittal images, with measurements taken in the affected disc segment and contiguous segments. The change in fluid content will be expressed as the ratio of fluid content at month 12 versus baseline. Secondary endpoints will assess disability and quality of life evolution using Short Form (SF)-36 scores, global assessments by the patient and physician, changes in rescue painkiller medication usage, drug consumption, employment and work status, medical and non-medical costs, immune response, and safety outcomes.