Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Immune System Diseases

Rare Diseases

Neoplasm Metastasis

Sclerosis

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Autoimmune Diseases

Atrophy

Autoimmune Diseases of the Nervous System

Disease Progression

Demyelinating Autoimmune Diseases, CNS

Demyelinating Diseases

Neoplastic Processes

Disease Attributes

Chronic Disease

Chronic Graft Versus Host Disease

All Drugs and Chemicals

Immunomodulating Agents

30-45 x 10E6 total cells in 2 ml. Subjects receive two annual courses of 5 subcutaneous doses each year (at 0, 4, 8, 12 and 24 weeks).

Tcelna inactive ingredients (without cells) totaling 2 ml per dose. Administered subcutaneously with same two year treatment regimen as experimental treatment arm.

Autologous pool of myelin reactive T-cells (MRTC) expanded ex vivo with immunodominant epitopes selected from the three myelin antigens, MBP, PLP and MOG on a per subject basis. Attenuated by irradiation to prevent further proliferation before releasing product for administration.

Tcelna

2 ml of Tcelna excipients, prepared daily as individual doses and irradiated before releasing product for administration.

Placebo

Jessica Jackson

The purpose of this study is to determine whether Tcelna (imilecleucel-T, autologous T-Cell Immunotherapy) is effective in the treatment of secondary progressive multiple sclerosis (SPMS).

Subjects whose myelin reactive T-cell can be identified by EPA will are randomized and provide blood to manufacture Tcelna. Approximately 5 weeks after receipt of the subject's whole blood procurement, the subjects will receive either Tcelna or placebo and will complete baseline assessments and will receive study treatments at Weeks 0, 4, 8, 12, and 24 (Visits 3-7), totaling 5 doses in year one.

Approximately one month prior to the Week 52 visit a second blood procurement will be performed and the subject will receive the second series of treatments as received in the first year study schedule. Subjects will be evaluated for changes in disability and cognitive function every 3 months, and radiographic changes annually.

Study of Tcelna (Imilecleucel-T) in Secondary Progressive Multiple Sclerosis

A Phase 2 Double-Blind, Placebo Controlled Multi-Center Study to Evaluate the Efficacy and Safety of Tcelna in Subjects With Secondary Progressive Multiple Sclerosis

The percentage of brain volume change (atrophy) as measured on 24 month MRIs calculated by the central MRI facility.

The percentage of subjects with sustained progression with definitions of sustained effect at 3 months and 6 months.

Opexa Therapeutics, Inc.

Channel Blockers

Natriuretic Agents

Psychotropic Drugs

Anticonvulsants

Neuroprotective Agents

Amiloride

Fluoxetine

Riluzole

Selective Serotonin Reuptake Inhibitors

Serotonin

Neurotransmitter Agents

Antidepressive Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Excitatory Amino Acid Antagonists

Protective Agents

Diuretics

Sodium Channel Blockers

Diuretics, Potassium Sparing

Amiloride 5 mg twice per day (5 mg once per day for first 4 weeks) for 96 weeks

Riluzole 50 mg twice per day (50 mg once per day for first 4 weeks) for 96 weeks

Fluoxetine 20 mg twice per day (20 mg once per day for first 4 weeks) for 96 weeks

Matched placebo 1 capsule twice per day (1 capsule a day for first 4 weeks) for 96 weeks

Jeremy Chataway

Siddharthan Chandran

Multiple sclerosis (MS) is a disabling and progressive neurological disease that affects approximately 100,000 people in the UK. Many patients with MS experience two phases of disease; early MS (also called relapsing remitting MS, RRMS) and late MS (also called secondary progressive MS (SPMS). Early MS is due to inflammation of the nerves and the insulation (called myelin) that surrounds the nerves. Early MS is often characterised by periods of "attacks" interspersed with periods of "remission" with no or low disease symptoms. Late or progressive MS, which affects the majority of patients and typically emerges after 10-15 years of disease, results from actual nerve death (also called neurodegeneration). The progressive stage of disease results not in individual attacks but slow, cumulative and irreversible disability affecting walking, balance, vision, cognition, pain control, bladder and bowel function. Critically, and unlike early disease, there is no proven treatment for the late stage of MS. This is therefore an urgent and major unmet health need. MS-SMART directly addresses this need and will evaluate in this clinical trial three drugs (fluoxetine, riluzole or amiloride), all of which have shown some promise in MS, and in particular in SPMS. The trial is randomised and blinded. Randomisation means patients can get any one of the three active drugs or the inactive placebo/dummy; blinded means that neither patients nor the doctors will know which drug or placebo patients are receiving. Randomisation and blinding are standard approaches in clinical trials to ensure unbiased testing of drugs. All patients in MS-SMART will have periodic MRI (magnetic resonance imaging) brain scans and after 96 weeks these will be analysed. We will then compare the scans of each drug to the placebo or dummy to see if any of the drugs slow the rate of brain shrinkage that normally occurs in SPMS. This measured change in brain size is the primary (major) outcome of MS-SMART.

MS-SMART will test the efficacy and mechanism of action of three repurposed drugs (fluoxetine, riluzole and amiloride). All three drugs are in human use and have a good safety record. Critically for the purpose of MS-SMART they all have shown promise in early phase human MS clinical trials and target one or more of the pivotal neurodegenerative causing pathways implicated in SPMS. This is a Type B trial, as the IMPs are all in human use, have a good safety profile but are not currently used for this patient population.

The major need for patients with established and progressive MS is neuroprotective or disease modifying treatments that will slow or even stop disease progression. This study will evaluate three highly promising putative neuroprotective drugs as well as comprehensively address several of the current knowledge gaps related to the understanding of neuroprotection and neurodegeneration in SPMS through MRI and CSF examination.

MS-SMART is a multicentre, multi-arm, double blind, placebo-controlled phase IIb randomised controlled trial. A total of 440 patients with SPMS, with an entry criteria of an EDSS score of 4.0-6.5 will be equally randomised to receive placebo or one of the three active agents (fluoxetine 20mg bd, amiloride 5mg bd or riluzole 50mg bd). Patients will be followed up for 96 weeks with outcome-data collected after 0, 24, 48 and 96 weeks. That is, the duration of the trial for a trial participant is 96 weeks (a telephone assessment at week 100, 4 weeks post completion will be conducted). This is standard practice for phase II trials in SPMS.

MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial

A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.

Persistent new T1 hypointense lesion count to assess neuroprotection in new lesions.

Grey matter volume change to assess cortical neuroprotection.

MR spectroscopy (MRS) to measure N-acetyl aspartate (reversal of neuronal mitochondrial dysfunction), myoinositol (prevention of glial cell inflammation) and glutamate (prevention of excitotoxicity).

Magnetic Transfer Ratio (MTR) to evaluate myelination.

Cervical cord imaging to assess cord neuroprotection.

Composite MRI/disability scores to increase sensitivity and study interaction of treatment mechanisms.

Quantification of Cerebrospinal fluid (CSF) neurofilament levels to measure neuroprotection.

Optical Coherence Tomography (OCT) measured Retinal Nerve Fibre Layer (RNFL) thickness as a measure of neuroprotection.

To establish whether a drug, from a panel of 3 leading candidate neuroprotective drugs, slows the rate of brain volume loss in SPMS over 96 weeks using MRI-derived percentage brain volume change (PBVC).

To establish that a multi-arm trial strategy is an efficient way of screening drugs in SPMS and can become the template for future work.

To explore any anti-inflammatory drug activity using the count of new and enlarging T2 lesions.

Examining for evidence of pseudo-atrophy (to ensure reliability of the primary outcome measure).

To examine the clinical effect of neuroprotection as measured by clinician - EDSS, MSFC, SDMT, SLCVA, relapse rate and patient reported outcome measures - MSIS29 v2, MSWS v2, Pain - NPRS and BPI and Fatigue - NFI.

To collect basic health economic data (EQ-5D) to inform future phase III trials.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Tcelna (Imilecleucel-T) in Secondary Progressive Multiple Sclerosis	NCT01684761	Autoimmune Dise... Multiple Sclero... Secondary Progr... Disease Progres... Brain Atrophy	Tcelna Placebo	18 Years - 60 Years	Opexa Therapeutics, Inc.
MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial	NCT01910259	Secondary Progr...	Amiloride Riluzole Fluoxetine Placebo	25 Years - 65 Years	University College, London

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