Amyotrophic Lateral SclerosisPhase 2STEMALSNCT06344260
Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis (STEMALS)
A Phase 2 study testing human Neural Stem Cells (hNSC) in people with Amyotrophic Lateral Sclerosis, run by Casa Sollievo della Sofferenza IRCCS at 4 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- human Neural Stem Cells (hNSC)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 4 sitesItaly
- Study dates
- 25 Jan 2024to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy4 sites, 4 recruiting
- Recruiting
Centro SLA Azienda Ospedaliera Università Maggiore della Carità
Novara, 28100
Letizia Mazzini, MD, +39 0321 3733962, ambulatorio.sla@maggioreosp.novara.it
- Not yet recruiting
Azienda Ospedaliera di Padova
Padua, 35128
Gianni Sorarù, MD, +39049-8213645/646, cl.neurologica@aopd.veneto.it
- Not yet recruiting
Azienza Ospedaliera Universitaria - Policlinico "P. Giaccone" Università degli Studi di Palermo
Palermo, 90129
Vincenzo La Bella, MD, +39 091 6555158, info@centroslapalermo.it
- Not yet recruiting
Casa Sollievo Della Sofferenza IRCCS
San Giovanni Rotondo, Foggia, 71013
About this study
Official title: Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis: A Multicenter, Randomized Placebo Controlled and Biological Endpoints Clinical Trial
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.
Read the 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
- Being tested
- human Neural Stem Cells (hNSC), Saline (Placebo)
- Keywords
- Neural Stem Cells, ALS, Biomarkers, ICV Surgery
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
human Neural Stem Cells (hNSC)Procedure or surgery
Also called Injection of human neural stem cells into brain lateral ventricle
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 (Placebo)Procedure or surgery
Also called Injection of saline into brain lateral ventricle
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.
| Study group | Role | What they receive |
|---|---|---|
| hNSC 20*10^6 | Experimental | Inoculation of 20*10^6 neural stem cells into the right lateral ventricle through a silicone catheter Receives: 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 Receives: 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 Receives: Procedure: Saline (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of treatment
safety assessed with respect to the incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) over the whole study period
Measured: From date of enrollment until 12 month.
Secondary outcomes (1)
Biological Endpoints
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 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.
disease
Measured: Samples for biological endpoints will be taken at treatment, 1, 3, and 6 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2024
- Study start25 Jan 2024
- Primary completionMar 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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)
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Casa Sollievo della Sofferenza IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Italy
- Responsible party
- Sponsor
- Investigators
- Angelo L Vescovi, PhD, Study director, Scientific Director Fondazione IRCCS "Casa Sollievo della Sofferenza"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06344260
- Sponsor's protocol ID
- hNSCALSII
- Acronym
- STEMALS
- Status last verified
- Mar 2024
- First submitted
- 18 Mar 2024
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis: A Multicenter, Randomized Placebo Controlled and Biological Endpoints Clinical Trial
- ClinicalTrials.gov ID
- NCT06344260
- Acronym / sponsor ID
- STEMALS / hNSCALSII
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Neural Stem Cells, ALS, Biomarkers, ICV Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Casa Sollievo della Sofferenza IRCCSUniversity, hospital or other
- Collaborators
- Ministry of Health, Italy
- Study start
- 25 Jan 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 3 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| hNSC 20*10^6 | Experimental | Procedure: human Neural Stem Cells (hNSC)Inoculation of 20*10^6 neural stem cells into the right lateral ventricle through a silicone catheter |
| hNSC 40*10^6 | Experimental | Procedure: human Neural Stem Cells (hNSC)Inoculation of 40*10^6 neural stem cells into the right lateral ventricle through a silicone catheter |
| Saline Solution (placebo) | Placebo comparator | Procedure: Saline (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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| human Neural Stem Cells (hNSC)Also: Injection of human neural stem cells into brain lateral ventricleThe 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 or surgery | hNSC 20*10^6, hNSC 40*10^6 |
| Saline (Placebo)Also: Injection of saline into brain lateral ventricleThe 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 or surgery | Saline Solution (placebo) |
Primary outcome
Safety of treatment
Time frame: From date of enrollment until 12 month.
safety assessed with respect to the incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) over the whole study period
1 secondary outcome
Biological Endpoints
Time frame: Samples for biological endpoints will be taken at treatment, 1, 3, and 6 months after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Angelo L Vescovi, PhD study director
Scientific Director Fondazione IRCCS "Casa Sollievo della Sofferenza"
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing human Neural Stem Cells (hNSC) in people with Amyotrophic Lateral Sclerosis, run by Casa Sollievo della Sofferenza IRCCS at 4 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Massimo Carella, PhD (+390882835928, m.carella@operapadrepio.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of treatment (time frame: From date of enrollment until 12 month.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.