POTASSIUM CHLORIDE PH. EUR., SODIUM CHLORIDE PH. EUR. for Amyotrophic lateral sclerosis

Inclusion criteria

• {"criterion_text":"- Patient provides written informed consent, informed consent signature collection prior to any study procedure (patient has good acceptance and understanding of the informed consent);\n- Presence of a willing and able caregiver who understands the need to attend all follow-up visits, even if mobility declines.\n- Definite, probable diagnosis according to the revised El Escorial criteria;\n- Age: 18-65 years;\n- FVC ≥ 70%;\n- Onset ≤ 24 months;\n- Patients with an ALSFRS-R score of at least 26; overall, including a score of at least 2 on each of the 1-9 ALSFRS-R individual component items and of at least 3 of the 10-12 individual components items;\n- Evidence of fast progression of the disease. We exclude slow progressors at the time of screening defined as Patient with an ALSFRS-R total score progression between onset of the disease and screening of < 0.3 per month. We document the fast progression of the disease defined as ALSFRS-R total score decrease of ≥ 1 point per month during a 12 week run-in period between screening and randomization;\n- Patient should be on a stable dose of Riluzole for > 30 days from pre-screening visit or not taking riluzole at all, nor plan to begin riluzole during the study period;\n- Patient is medically able to tolerate transient immunosuppression regimen;"}

Exclusion criteria

• {"criterion_text":"- Psychiatric disease or other neurological diseases different from ALS\n- Patient has participated in another clinical treatment trial or received other experimental medications outside of a clinical trial within 1 month prior to start of this study.\n- Evidence of any concurrent illness or treatments limiting the safety to participate or any condition that the neurosurgeon feels may pose complications for the surgery;\n- Cancer within the previous 10 years;\n- Immunosuppressive therapy within 12 weeks of screening; active autoimmune disease or infection (including hepatitis B, hepatitis C, or HIV);\n- Cognitive impairment;\n- Contraindications to perform MRI scans, CSF withdrawal and Skin biopsy\n- Patient unable to understand informed consent form;\n- Pregnancy and breast feeding;\n- Patient has been treated previously with any stem cell or somatic cells therapy;"}

Primary endpoints

• {"endpoint_text":"- Incidence of adverse events directly related to the IMP, infusion site reactions, clinically relevant changes in neurologic function, laboratory values, and vital signs","definition_or_measurement_approach":"Safety assessed with respect to the incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) over the whole study period. AEs are coded using MedDRA and reported to competent authorities if unexpected and related to intracerebroventricular administration of human Neural Stem Cells."}

Secondary endpoints

• {"endpoint_text":"- To compare the change in slopes in points per month (≥0.5 to ≥2.5 for responders) from the pre-transplantation period to the post transplantation period in ALSFRS-R between the treatment and placebo groups through 3 months post first transplantation","definition_or_measurement_approach":"Compare change in slopes (points/month) of ALSFRS-R from pre- to post-transplantation between treatment and placebo up to 3 months after first transplantation."}
• {"endpoint_text":"- To compare the change in slopes from the pre-transplantation period to the post transplantation period in FVC (≥25% to ≥100% change for responders) between the treatment and placebo groups through 3 months post first transplantation","definition_or_measurement_approach":"Compare change in slopes of FVC from pre- to post-transplantation between treatment and placebo through 3 months post first transplantation; responder thresholds defined as ≥25% to ≥100% change."}
• {"endpoint_text":"- To compare the slope of the rate of decline in the ALSFRS-R at 3 and 6 months following first transplantation relative to the 3-4 months baseline period before transplantation in all patients (both treatment and placebo groups).","definition_or_measurement_approach":"Compare slope of ALSFRS-R decline at 3 and 6 months post-first transplantation relative to 3-4 month baseline period; includes all patients."}
• {"endpoint_text":"- To compare the slope of the rate of decline in FVC at 3 and 6 months following first transplantation relative to the 3-4 months baseline period before transplantation in all patients (both treatment and placebo groups).","definition_or_measurement_approach":"Compare slope of FVC decline at 3 and 6 months post-first transplantation relative to 3-4 month baseline period; includes all patients."}
• {"endpoint_text":"- To collect data on the impact of hNSC transplantation on quality of life as measured by ALSAQ-40 scale","definition_or_measurement_approach":"Quality of life measured using ALSAQ-40 scale; data collected post-transplantation to assess impact."}
• {"endpoint_text":"- To evaluate the biological activity of hNSC treatment by measuring the levels of selected pharmacodynamics biomarkers in CSF and serum. Data will be statistically assessed for significance by either Student t test or analysis of variance as applicable. A p value of less than 0.05 will be considered statistically significant. Candidate markers include: lNf, GFAP, NF1, VEGF, Osteopontin, CXCL13, Cystatina, MCP-1 BDNF, YKL-40, IL-6, TNF-a, IL-17, TDP43 TAU.","definition_or_measurement_approach":"Pharmacodynamic biomarkers measured in CSF and serum; statistical analysis via Student t-test or ANOVA as applicable, significance threshold p<0.05. Candidate markers listed explicitly."}
• {"endpoint_text":"- In parallel to the clinical evaluation of hNSCs efficacy we will also develop patient-specific cell models in order to individuate molecular and cellular mechanisms supporting the putative therapeutic action of hNSCs treatment. These models will be derived from blood or skin cells of the patients recruited in the trial in order to produce iPS cells, then differentiated in NSCs.","definition_or_measurement_approach":"Development of patient-specific cellular models from patient blood or skin cells to produce iPS cells and differentiate into NSCs to investigate molecular/cellular mechanisms; descriptive and exploratory laboratory work."}

Italy

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

18-11-2024

Processing Time Days

38

Number Of Sites

4

Number Of Participants

30

Primary sponsor

Full Name

Casa Sollievo Della Sofferenza

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy