Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis: A multicenter, randomized placebo controlled and biological endpoints clinical Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Casa Sollievo Della Sofferenza

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Diseases [C] - Nervous System Diseases [C10]

Trial duration

24 Jan 2024 → ongoing

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministry of Health

External identifiers

EU CT number

2024-518888-35-00

EudraCT number

2018-002373-22

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary trial outcome is 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 they should be reported to competent authorities only if unexpected and related to Intracerebroventricular administration of human Neural Stem Cells.

Secondary objectives 1

1. The secondary aim is to measure the effects of the treatment on the progression of the disease

Conditions and MedDRA coding

amyotrophic lateral sclerosis patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 10

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of adverse events directly related to the IMP, infusion site reactions, clinically relevant changes in neurologic function, laboratory values, and vital signs

Secondary endpoints 7

1. 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
2. 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
3. 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).
4. 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).
5. To collect data on the impact of hNSC transplantation on quality of life as measured by ALSAQ-40 scale
6. 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.
7. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Casa Sollievo Della Sofferenza

Sponsor organisation

Casa Sollievo Della Sofferenza

Address

Viale Convento Cappuccini 1

City

San Giovanni Rotondo

Postcode

71013

Country

Italy

Scientific contact point

Organisation

Casa Sollievo Della Sofferenza

Contact name

Massimo Carella

Public contact point

Organisation

Casa Sollievo Della Sofferenza

Contact name

Massimo Carella

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications