Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis (STEMALS)

NCT06344260 | Recruiting Phase 2 DMC

• 1 other identifier: hNSCALSII
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Neural Stem Cells; ALS; Biomarkers; ICV Surgery

Outcome Measures

Primary Outcomes (1)

• Safety of treatment

  safety assessed with respect to the incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) over the whole study period

  From date of enrollment until 12 month.

Secondary Outcomes (1)

• Biological Endpoints

  Samples for biological endpoints will be taken at treatment, 1, 3, and 6 months after treatment

Study Arms (3)

hNSC 20*10^6

EXPERIMENTAL

Inoculation of 20\*10\^6 neural stem cells into the right lateral ventricle through a silicone catheter

Procedure: human Neural Stem Cells (hNSC)

hNSC 40*10^6

EXPERIMENTAL

Inoculation of 40\*10\^6 neural stem cells into the right lateral ventricle through a silicone catheter

Procedure: human Neural Stem Cells (hNSC)

Saline Solution (placebo)

PLACEBO COMPARATOR

Inoculation of saline (placebo) into the right lateral ventricle through a silicone catheter 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 (period of time considered the minimum for a correct clinical evaluation that does not risk having to exclude patients treated with placebo from subsequent treatment with cells due to excessive physical decline), 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

Procedure: Saline (Placebo)

Interventions

human Neural Stem Cells (hNSC) PROCEDURE

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.

Also known as: Injection of human neural stem cells into brain lateral ventricle

hNSC 20*10^6; hNSC 40*10^6

Saline (Placebo) PROCEDURE

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.

Also known as: Injection of saline into brain lateral ventricle

Saline Solution (placebo)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient provides written informed consent, informed consent signature collection prior to any study procedure (patient has good acceptance and understanding of the informed consent);
• Definite, probable diagnosis according to the revised El Escorial criteria;
• Age: 18-65 years;
• FVC \>70%;
• Onset ≤ 24 months;
• 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;
• 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;
• 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;
• Patient is medically able to tolerate transient immunosuppression regimen;
• Presence of a willing and able caregiver who understands the need to attend all follow-up visits, even if mobility declines.

You may not qualify if:

• Psychiatric disease or other neurological diseases different from ALS;
• 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;
• Cancer within the previous 10 years;
• Immunosuppressive therapy within 12 weeks of screening; active autoimmune disease or infection (including hepatitis B, hepatitis C, or HIV);
• Cognitive impairment;
• Contraindications to perform MRI scans, CSF withdrawal and Skin biopsy;
• Patient unable to understand informed consent form;
• Pregnancy and breast feeding;
• Patient has been treated previously with any stem cell or somatic cells therapy;
• 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.

Sponsors & Collaborators

• Casa Sollievo della Sofferenza IRCCS: lead
• Ministry of Health, Italy: collaborator

Study Sites (4)

Casa Sollievo Della Sofferenza IRCCS

San Giovanni Rotondo, Foggia, 71013, Italy

NOT YET RECRUITING

Centro SLA Azienda Ospedaliera Università Maggiore della Carità

Novara, 28100, Italy

RECRUITING

Azienda Ospedaliera di Padova

Padua, 35128, Italy

NOT YET RECRUITING

Azienza Ospedaliera Universitaria - Policlinico "P. Giaccone" Università degli Studi di Palermo

Palermo, 90129, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Angelo L Vescovi, PhD

  Scientific Director Fondazione IRCCS "Casa Sollievo della Sofferenza"

  STUDY DIRECTOR

Central Study Contacts

Massimo Carella, PhD

CONTACT

+390882835928; m.carella@operapadrepio.it

CTO Clinical Trial Office

CONTACT

+390882410997; clinicaltrialoffice@operapadrepio.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In order to blind also the statistician that will analyse the results the protocol has been designed as a triple-blinded protocol. This means that both the researchers, which include neurologist, neurosurgeon and biologist, as well as the patients and the statisticians are unaware of whether the participant received the treatment or the placebo (only IMP Manufacturer QP is unblinded since release the cell drug to the use in the surgery room)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an approximate 24-months triple-blinded, randomized, controlled vs placebo, in three arms study (PHASE B). 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. In the phase B three arms will be: 1) hNSCs 20 milion cells 2) hNSCs 40 milion cells 3) Saline (comparator)

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: April 3, 2024
• Study Start: January 25, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 3, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)