NCT06344260

Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis (STEMALS)

Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis: A Multicenter, Randomized Placebo Controlled and Biological Endpoints Clinical Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Casa Sollievo della Sofferenza IRCCS · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

A Not for Profit Phase II Study to Evaluate Safety, Efficacy and Biomarkers secondary endpoints of Human Neural Stem cell intracerebroventricular transplantation in amyotrophic lateral sclerosis patients: a randomized, placebo controlled, triple blind study. This is an approximate 24-months study (PHASE B) consisting, per patient, of a 30-day screening period, 12-month enrollment and follow up period. A preliminary 3+3 dose-escalation open-label phase (PHASE A) will be performed in order to test the toxicity of the two proposed cell doses. The study will be stopped when all the subjects included in the treatment period complete the study visits. The study uses an ATMP, for that reason all the patients follow up will be prosecuted long life.

Detailed description

Phase A: Open, monocentric safety, dose-finding study: The hNSCs will be produced by the UPTA (Unità Produttiva per Terapie Avanzate) of "Casa Sollievo della Sofferenza" according to GMP guidelines and injected using an Ommaya reservoir which will be removed immediately after the transplant procedure. The reservoir consists of an indwelling ventricular catheter with a dome-shaped collapsible silicone reservoir port positioned under the scalp. The distal end of the catheter is surgically positioned into the ipsilateral ventricle and connected to the reservoir. Six patients affected by ALS will be consecutively enrolled after pre- and screening visits. Thereafter, the first three patients will receive 20 million of hNSCs. If none of the three patients will present a serious adverse event classified as related to the study treatment, the dose level will be escalated up to 40 million of hNSCs for the next and last cohort of three patients. An Independent Data Safety Monitoring Board (DSMB) will oversee the safety of the Study Subjects on an ongoing basis, will review all safety data and issue a final recommendation at the end of this phase. Phase B: randomized, controlled vs placebo, in three arms, with two different doses of 20 and 40 \*10\^6 cells transplanted using an Ommaya reservoir. The reservoir will be placed to all recruited patients in a first surgical session, after randomization half of the subjects will receive the drug product (further randomized for doses) and half the placebo. After three months, patients that already received cells will also be infused with placebo while the others will be randomized and transplanted with one of the two cell doses previously mentioned. This secondary randomization will be performed to provide experimental treatment to all patients and is not intended as a second stage of a cross-over study. In the second surgical session the Ommaya reservoir will be removed and patients will be monitored for 3 months after that.

Conditions

• Amyotrophic Lateral Sclerosis

Interventions

Type	Name	Description
PROCEDURE	human Neural Stem Cells (hNSC)	The patient is placed on a regular operating room table with or without rigid head fixation. Procedure will be performed whether under general anesthesia or sedation and local anesthesia. Image guidance will be registered using the frameless stereotactic AxiEM system. Image guidance will be used to perform ventricular cannulation with the catheter passed over an electromagnetic-tipped stylet, which is recognized and tracked by the navigation system. The correct placement of the catheter is verified by the egress of CSF. Finally the electromagnetic stylet will be removed and a Rickam reservoir connect to ventricular catheter. Operative time will be about 30 minute. A post-operative CT scan will be obtained in all patients to confirm the catheter position.
PROCEDURE	Saline (Placebo)	The patient is placed on a regular operating room table with or without rigid head fixation. Procedure will be performed whether under general anesthesia or sedation and local anesthesia. Image guidance will be registered using the frameless stereotactic AxiEM system. Image guidance will be used to perform ventricular cannulation with the catheter passed over an electromagnetic-tipped stylet, which is recognized and tracked by the navigation system. The correct placement of the catheter is verified by the egress of CSF. Finally the electromagnetic stylet will be removed and a Rickam reservoir connect to ventricular catheter. Operative time will be about 30 minute. A post-operative CT scan will be obtained in all patients to confirm the catheter position.

Timeline

• Start date: 2024-01-25
• Primary completion: 2027-03-01
• Completion: 2027-09-01
• First posted: 2024-04-03
• Last updated: 2024-04-03

Locations

4 sites across 1 country: Italy