Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis (STEMALS)

NCT ID: NCT06344260

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-25
• Study Completion Date: 2027-09-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

hNSC 20*10^6

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

Group Type: EXPERIMENTAL

human Neural Stem Cells (hNSC)

Intervention Type: 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.

hNSC 40*10^6

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

Group Type: EXPERIMENTAL

human Neural Stem Cells (hNSC)

Intervention Type: 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.

Saline Solution (placebo)

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

Group Type: PLACEBO_COMPARATOR

Saline (Placebo)

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Other Intervention Names

Injection of human neural stem cells into brain lateral ventricle; Injection of saline into brain lateral ventricle

Eligibility Criteria

Inclusion Criteria

1. Patient provides written informed consent, informed consent signature collection prior to any study procedure (patient has good acceptance and understanding of the informed consent);

2. Definite, probable diagnosis according to the revised El Escorial criteria;

3. Age: 18-65 years;

4. FVC >70%;

5. Onset ≤ 24 months;

6. 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;

7. 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;

8. 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;

9. Patient is medically able to tolerate transient immunosuppression regimen;

10. Presence of a willing and able caregiver who understands the need to attend all follow-up visits, even if mobility declines.

Exclusion Criteria

1. Psychiatric disease or other neurological diseases different from ALS;

2. 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;

3. Cancer within the previous 10 years;

4. Immunosuppressive therapy within 12 weeks of screening; active autoimmune disease or infection (including hepatitis B, hepatitis C, or HIV);

5. Cognitive impairment;

6. Contraindications to perform MRI scans, CSF withdrawal and Skin biopsy;

7. Patient unable to understand informed consent form;

8. Pregnancy and breast feeding;

9. Patient has been treated previously with any stem cell or somatic cells therapy;

10. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Italy

OTHER_GOV

Sponsor Role: collaborator

Casa Sollievo della Sofferenza IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angelo L Vescovi, PhD

Role: STUDY_DIRECTOR

Scientific Director Fondazione IRCCS "Casa Sollievo della Sofferenza"

Locations

Casa Sollievo Della Sofferenza IRCCS

San Giovanni Rotondo, Foggia, Italy

Site Status: NOT_YET_RECRUITING

Centro SLA Azienda Ospedaliera Università Maggiore della Carità

Novara, , Italy

Site Status: RECRUITING

Azienda Ospedaliera di Padova

Padua, , Italy

Site Status: NOT_YET_RECRUITING

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

Palermo, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

Massimo Carella, PhD

Role: CONTACT

m.carella@operapadrepio.it

+390882835928

CTO Clinical Trial Office

Role: CONTACT

clinicaltrialoffice@operapadrepio.it

+390882410997

Facility Contacts

Letizia Mazzini, MD

Role: primary

ambulatorio.sla@maggioreosp.novara.it

+39 0321 3733962

Gianni Sorarù, MD

Role: primary

cl.neurologica@aopd.veneto.it

+39049-8213645/646

Vincenzo La Bella, MD

Role: primary

info@centroslapalermo.it

+39 091 6555158

Other Identifiers

hNSCALSII

Identifier Type: -

Identifier Source: org_study_id