Smart-Ms

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 May 2024 → ongoing

Decision date (initial)

2024-04-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

KLINBEFORSK

External identifiers

EU CT number

2023-510228-63-00

EudraCT number

2020-002373-95

ClinicalTrials.gov

NCT04749667

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

The primary objective of the study is to investigate neuroregenerative efficacy (proof of concept) of intrathecal treatment with autologous MSCs as measured by neurophysiological parameters in patients with progressive MS.

Secondary objectives 1

1. Secondary objectives are to assess neuroregenerative efficacy as measured by other neurophysiological, opthalmological and MRI modalities and to assess safety.

Conditions and MedDRA coding

Multiple sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥18 to ≤55, both genders
2. Diagnosis of secondary progressive or primary progressive MS using revised McDonald criteria of clinically definite MS
3. An EDSS score of 4 to 7
4. Disease duration 2 - 18 years
5. Signed, written informed consent

Exclusion criteria 25

1. Treatment with cytotoxic medications during the last 3 months prior to inclusion
2. Any illness or prior/ongoing treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate autologous stem cell treatment
3. Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity
4. Current immunomodulatory/immunosuppressive treatment
5. Immunomodulatory/immunosuppressive treatment within 6 months prior to inclusion. This includes, but is not restricted to treatment with natalizumab, fingolimod, dimetylfumurat, glatiramer acetate, interferon beta medications, teriflunomide, and siponimod.
6. Treatment with kladribin, ocrelizumab, rituximab, and alemtuzumab within 12 months prior to inclusion
7. Treatment with hematopoietic stem cell therapy within 12 months prior to inclusion
8. Treatment with glucocorticoids or ACTH within three months prior to start of inclusion
9. Having experienced an MS relapse within 2 years prior to study inclusion
10. History of malignancy, other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year within the last 10 years
11. Severely limited life expectancy by another co-morbid illness
12. History of previous diagnosis of myelodysplasia or previous hematologic disease (including lymphoproliferative disease, bone marrow insufficiency or previous lymphoid irradiation) or current clinically relevant abnormalities of white blood cell counts
13. Immunocompromised patients
14. Estimated glomerular filtration rate <60 ml/min/1.73 m2 or known renal failure
15. Bleeding or clotting diathesis or the use of antithrombotic or anticoagulative treatment
16. Platelet (thrombocyte) count <100 x 10*9/L
17. Participation in another experimental clinical study with administration of another IMP within the preceding 12 months
18. Contraindications to MRI
19. Prior or current major depression
20. Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
21. Pregnancy or risk of pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study), breastfeeding or lactation
22. Known hypersensitivity against paracetamol, codein or xylocain
23. Diagnosis or strong suspicion of polyneuropathy
24. Prior or current alcohol or drug dependencies
25. Inability to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in CEP (VEP+SEP+MEP) at 6 months as compared to baseline between MSCs treatment vs. placebo (arm A vs. arm B)

Secondary endpoints 32

1. Difference in CEP at 12 months (study treatment 1 vs. study treatment 2)
2. Difference in VEP at 6 months (arm A vs. arm B)
3. Difference in VEP at 12 months (study treatment 1 vs. study treatment 2)
4. Difference in SEP at 6 months (arm A vs. arm B)
5. Difference in SEP at 12 months (study treatment 1 vs. study treatment 2)
6. Difference in MEP at 6 months (arm A vs. arm B)
7. Difference in MEP at 12 months (study treatment 1 vs. study treatment 2)
8. Difference in EDSS at 6 months (arm A vs. arm B)
9. Difference in EDSS at 12 months (study treatment 1 vs. study treatment 2)
10. Difference in MRI T2-weighted hyperintense lesion volume at 6 months (arm A vs. arm B)
11. Difference in MRI T2-weighted hyperintense lesion volume at 12 months (study treatment 1 vs. study treatment 2)
12. Difference in MRI T1-weighted hypointense lesion volume at 6 months (arm A vs. arm B)
13. Difference in MRI T1-weighted hypointense lesion volume at 12 months (study treatment 1 vs. study treatment 2)
14. Difference in brain volume at 6 months (arm A vs. arm B)
15. Difference in brain volume at 12 months (study treatment 1 vs. study treatment 2)
16. Difference in visual function (visual acuity, visual field, color vision and contrast sensitivity) at 6 months (arm A vs. arm B)
17. Difference in visual function (visual acuity, visual field, color vision and contrast sensitivity) at 12 months (study treatment 1 vs. study treatment 2)
18. Difference in retinal thickness measured with OCT at 6 months (arm A vs. arm B)
19. Difference in retinal thickness measured with OCT at 12 months (study treatment 1 vs study treatment 2)
20. Difference in Nine-Hole-Peg Test (9-HPT) score at 6 months (arm A vs. arm B)
21. Difference in Nine-Hole-Peg Test (9-HPT) score at 12 months (study treatment 1 vs. study treatment 2)
22. Difference in Timed 25 Foot Walk (T25FW) score at 6 months (arm A vs. arm B)
23. Difference in Timed 25 Foot Walk (T25FW) score at 12 months (study treatment 1 vs. study treatment 2)
24. Difference in the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), European Quality of Life 5 dimensions (EQ-5D-5L), Multiple Sclerosis Impact Scale (MSIS) and Fatigue severity scale (FSS) score at 6 months (arm A vs. arm B)
25. Difference in the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), European Quality of Life 5 dimensions (EQ-5D-5L), Multiple Sclerosis Impact Scale (MSIS) and Fatigue severity scale (FSS) score at 12 months (study treatment 1 vs. study treatment 2)
26. Difference in serum neurofilament light chain and GFAP at 6 months (arm A vs. arm B)
27. Difference in serum neurofilament light chain and GFAP at 12 monhts (study treatment 1 vs. study treatment 2)
28. Intraindividual CEP (longitudinal) between study treatment 1 vs. study treatment 2 in each patient
29. Rate and nature of adverse- and serious adverse events during 18 months of follow up
30. Clinical relevant changes in vital signs during 18 months of follow up
31. Clinical relevant changes on physical examinations during 18 months of follow up
32. Clinical relevant changes in clinical laboratory results during 18 months of follow up

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Haukelandsveien 22

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Christopher Elnan Kvistad

Public contact point

Organisation

Helse Bergen HF

Contact name

Christopher Elnan Kvistad

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

Application history

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