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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Autoimmune Diseases of the Nervous System, Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Disease Progression, Brain Atrophy

Intervention / Treatment
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* Biological: Tcelna
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with MS as defined by the modified McDonald criteria SPMS defined as relapsing-remitting disease with recent progression in MS-related neurological deficits EDSS score 3.0 - 6.0, inclusively Presence of myelin reactive T-cells Exclusion Criteria: Diagnosed with primary progressive MS Treatment with beta-interferon, glatiramer acetate or dimethyl fumarate 30 days prior to screening Treatment with ACTH, any over-the-counter or prescription corticosteroids 60 days prior to screening Treatment with IVIG, plasmapheresis or cytopheresis 90 days prior to screening Treatment with mitoxantrone, teriflunomide, fingolimod, natalizumab, azathioprine, cyclosporine, methotrexate or mycophenolate mofetil 1 year prior to baseline Any prior treatment with cladribine, cyclophosphamide, total lymphoid irradiation, T cell or T cell receptor products, or any therapeutic monoclonal antibody, except natalizumab Previous treatment with any other MS investigational drug 1 year prior to screening All non-MS investigational drugs must have a minimum washout of 30 days prior to screening or 5 half-lives, whatever is the longest period of time. HIV or hepatitis infection History of cancer Any other significant medical condition that, in the opinion of the investigator, could cause CNS tissue damage or limit its repair.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tcelna<br>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). | Biological: Tcelna<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Tcelna inactive ingredients (without cells) totaling 2 ml per dose. Administered subcutaneously with same two year treatment regimen as experimental treatment arm. | Biological: Placebo<br>* 2 ml of Tcelna excipients, prepared daily as individual doses and irradiated before releasing product for administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Atrophy | The percentage of brain volume change (atrophy) as measured on 24 month MRIs calculated by the central MRI facility. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Progression | The percentage of subjects with sustained progression with definitions of sustained effect at 3 months and 6 months. | 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multicenter Study, Randomized Controlled Trial, Individualized Medicine, Immunotherapy, Myelin Proteins, Biological Agents