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Plasma-lyte 148

One intrathecal (IT) administration of SCM-010 at baseline visit

SCM-010 is comprised of adipose derived expanded mesenchymal cells (ADSC), suspended in Plasma-Lyte and intended for intrathecal (IT) administration.

SCM-010

Arnon Karni, Dr.

Prospective, single center, open label, phase I/IIa escalating dose study. To evaluate the safety and efficacy of escalating doses of SCM-010 in subjects with SPMS.

Twelve (12) SPMS subjects will be enrolled in this study in two dose cohorts. Each subject will receive SCM- 010 by intrathecal (IT) administration at baseline and will be followed up for 24 weeks for efficacy and 48 weeks for safety.

Study to Assess the Safety and Efficacy of an IT Administration of SCM-010 in SPMS

A Prospective, Single Center, Open Label, Dose Escalation Phase I/IIa Study to Assess the Safety and Efficacy of an Intrathecal Administration of SCM-010 in Subjects With Secondary Progressive Multiple Sclerosis (SPMS)

Safety data will be collected following the one IT administration of SCM-010 at baseline visit

Changes in lesions from baseline MRI scan.

The Expanded Disability Status Scale (EDSS) will be measured during the study. range of the scale 0-10

CDP for an individual subject is defined as at least 3-months confirmed EDSS increase from baseline.

The Expanded Disability Status Scale (EDSS) will be measured during the study. range of the scale 0-10

Stem Cell Medicine Ltd.

Disease Progression

Lipid Regulating Agents

Simvastatin

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

* One (1 = 40mg) simvastatin tablet once daily at night for 1 month
* Two (2 = 80mg) simvastatin tablets once daily at night, for the next 35 months

* One (1) placebo tablet once daily at night for 1 month
* Two (2) placebo tablets once daily at night, for the next 35 months

Placebo

Jeremy Chataway

Multiple Sclerosis (MS) is a progressive neurological disorder of the brain and spinal cord. It affects approximately 120,000 people in the United Kingdom and 2.5 million people globally. Most people with MS experience two stages of the disease:

Early MS - Relapsing-Remitting MS (RRMS), which is partially reversible, and Late MS - Secondary Progressive MS (SPMS), which affects the majority of patients, usually after 10 to 15 years after diagnosis.

SPMS results from progressive neuronal degeneration that causes accumulating and irreversible disability affecting walking, balance, manual function, vision, cognition, pain control, bladder and bowel function. The pathological process driving the accrual of disability in SPMS is not known at present.

Immunomodulatory anti-inflammatory disease modifying therapies (DMTs) are increasingly effective in reducing relapse frequency in RRMS, however, they have been unsuccessful in slowing disease progression in SPMS. This is the overwhelming conclusion from an analysis of 18 phase 3 trials (n=8500), of which 70% of the population had SPMS, all performed in the last 25 years. There is no current disease modifying treatment (DMT) for SPMS.

In an earlier study (Multiple Sclerosis-Simvastatin 1; MS-STAT1), 140 people with SPMS were randomly assigned to receive either placebo or simvastatin for a period of two years. The investigators found that the rate of brain atrophy (loss of neurons - 'brain shrinkage'), as measured by magnetic resonance imaging (MRI), was reduced in patients receiving simvastatin compared to those taking placebo.

Several other long term studies have also reported that there might be a relationship between the rate of brain atrophy and the degree of impairment. The study is designed to test the effectiveness of repurposed simvastatin (80mg) in a phase 3 double blind, randomised, placebo controlled trial (1:1) in patients with secondary progressive MS (SPMS), to determine if the rate of disability progression can be slowed over a 3 year period.

The results generated from this trial may help to improve the treatment options of people with MS. In addition, taking part in this trial will mean regular review by an experienced neurologist regardless of the drug that patients are randomly allocated to receive.

Multiple Sclerosis-Simvastatin Trial 2

A Phase 3 Randomised, Double Blind, Clinical Trial Investigating the Effectiveness of Repurposed Simvastatin Compared to Placebo, in Secondary Progressive Multiple Sclerosis, in Slowing the Progression of Disability

The initial disability progression event is finalised as positive if disability is sustained and confirmed ≥6\* months later. Progression of disability defined as an increase of at least 1 point if EDSS baseline score \<6, or an increase of 0.5 point if baseline EDSS score is ≥6.

MSWS-12v2 is a12 item patient report measure on the impact of MS on the individual's walking ability over the previous 2 weeks. Each item will be summed to generate a total score and transformed to a scale with a range of 0 to 100 with high scores indicating greater impact on walking.

MS Impact Scale-29 version 2 (MSIS-29v2) - A psychometrically validated patient-reported outcome measure increasingly used for measuring the impact of MS on people's lives. The 29-item scale assesses the impact of MS on people's health related quality of life in terms of their physical and psychological well-being over the previous 2 weeks.

To estimate the incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon using the Client Client Services Receipt Inventory Form.

T25-FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk

The 9HPT is a brief, standardized, quantitative test of upper extremity function. Participants are instructed to pick up 9 pegs, one at a time, as quickly as possible and are required to insert them into 9 empty peg holes. Once all nine pegs have been inserted, the participant should immediately remove the pegs, one at a time. The total time taken to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged.

mRS is used to evaluate the degree of disability in daily activities of those with neurological disability.

A relapse will be defined as new or worsening neurological symptom(s) in the absence of fever, lasting for more than 24 hours, and have been preceded by a period of clinical stability of at least 30 days, with no other explanation than MS.

Sloan chart testing is a reliable, quantitative, and clinically practical measure of visual function that will be administered by trained assessors. The chart consists of rows of grey letters on a white background. Letters are displayed in decreasing order from the top of the chart to the bottom. Testing will be conducted at three different contrast levels (100%, 2.5% and 1.25%). The chart will be scored based on the number of letters correctly identified out of 60.

EQ-5D 5L is a 5 item questionnaire (assessing - mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and visual analogue scale (VAS) enables calculation of quality adjusted life years (QALY) to enable health economic analyses to be performed. Each dimension assessed has 5 response scales to select from: no problems, slight problems, moderate problems, severe problems, and extreme problems

A Modified Multiple Sclerosis Functional Composite (MSFC) score comprised of 3 components (T25FW, 9HPT, SDMT). The Symbol digit modalities test (SDMT) will replace the Paced Auditory Serial Addition Test (PASAT), one of the three components in the Standard MSFC.

BICAMS is a composite cognitive assessment tool comprising of the three components : Symbol Digit Modalities Test (SDMT) , California Verbal Learning Test-II (CVLT-II) and Brief visuospatial memory test- Revised (BVMT-R)

SDMT is a brief measure of cognitive processing speed. It measures information processing speed for visually presented stimuli, but is self-paced, with at least equal reliability and sensitivity to the presence of worsening cognitive impairment.

A secondary composite progression outcome measure defined as one or more of: ≥20% increase in time taken to complete the 25 Foot Walk (T25FW); or ≥20% increase in time to complete 9 Hole Peg Test (9HPT); or increase in EDSS (0.5 point increase if baseline ≥6 /1.0 point increase if baseline \<6). The initial disability progression event will be finalised as positive if it is sustained and confirmed ≥6 months later\*. The time to event analysis will be from randomisation until date of the initial disability progression (if subsequently confirmed)

A questionnaire measuring the severity of physical and mental fatigue. The total score range is minimum of 0 and maximum of 33.

For the subscales, physical fatigue score has a minimum of 0 and maximum of 21. The Mental fatigue score has a minimum of 0 and maximum of 12.

The CSRI is a questionnaire that collects information on service utilisation, income, accommodation and other cost-related variables. Its primary purpose is to allow resource use patterns in each of the two arms to be described, and support costs to be estimated for health economics purposes.

University of Edinburgh

Queen Mary University of London

London School of Hygiene and Tropical Medicine

University of Leeds

The Leeds Teaching Hospitals NHS Trust

Imperial College Healthcare NHS Trust

University College, London

Siponimod

Immunosuppressive Agents

Immunologic Factors

Patients administered Mayzent by prescription

There is no treatment allocation. Patients administered Mayzent by prescription that have started before inclusion of the patient into the study will be enrolled.

Mayzent

Novartis Pharmaceuticals

This study is a single cohort, central registration system, all-case, open-label, multicenter observational study in patients using Mayzent for the indication of secondary progressive multiple sclerosis.

This is a non-interventional study, and as such there is no binding treatment strategy, diagnosis/treatment procedures or visit schedule. The investigator should administer Mayzent as labelled. Routine medical practice will apply to visit frequency and evaluation variables, and only these data will be collected by the sponsor as part of the study procedures. The investigator should record data in the applicable CRFs at every visit if possible.

Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients

Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients (Prevention of Relapses and Delay of Progression of Physical Disability in Secondary Progressive Multiple Sclerosis)

A SAE is defined as an AE whose description suggests that it is serious or whose outcome is fatal.

An adverse reaction is defined as an adverse event that is suspected by the investigator to be causally related to Mayzent or whose causality is not recorded

Secondary Progressive Multiple Sclerosis (SPMS) symptom changes will be assessed an rated as "very much improved", "improved", "unchanged", "worsening" or "not assessable" in comparison with the symptoms at the start of Mayzent administration

EDSS assesses disability. An overall score ranging from 0 (normal) to 10 (death due to MS) will be calculated.

Disability progression is defined as an increase of 1.5 points or more in patients with an EDSS score of 0 at baseline, an increase of 1 point or more in patients with an EDSS score of 0.5 to 5 at baseline and an increase of 0.5 points or more in patients with an EDSS score of 5.5 or more at baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Assess the Safety and Efficacy of an IT Administration of SCM-010 in SPMS	NCT03696485	Secondary Progr...	SCM-010	18 Years - 60 Years	Stem Cell Medicine Ltd.
Multiple Sclerosis-Simvastatin Trial 2	NCT03387670	Secondary Progr...	Simvastatin Placebo	25 Years - 65 Years	University College, London
Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients	NCT04593927	Secondary Progr...	Mayzent	- 99 Years	Novartis
Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients	NCT04593927	Secondary Progr...	Mayzent	- 99 Years	Novartis

Spots Global Cancer Trial Database for secondary progressive multiple sclerosis (spms)