The study seeks to investigate safety and efficacy of ixazomib (NINLARO), a proteasome inhibitor, in multiple sclerosis (MS). Participants will receive either ixazomib capsules or placebo capsules for up to 24 months.
Male and female patients 18 to 65 years old at screening
Patients with RRMS must be on DMT
Patients with progressive MS must not be on DMT
Participants with RRMS must be on stable DMT (i.e. must not have had a relapse within 1 month prior to the screening visit). Patients on tecfidera, cladribine, ocrelizumab, alemtuzumab, fingolimod or natalizumab must be enrolled with caution, at Chief Investigator's (CI) discretion because of the lymphopenia caused by these drugs and the risk of thrombocytopenia in 1-2 % of people after alemtuzumab
EDSS > 8.5 at screening
MS relapse within 1 month prior to screening
Female patients who are lactating or have a positive serum pregnancy test at screening
Major surgery within 14 days before baseline
Parallel
Ixazomib (NINLARO®) capsules / Matching placebo capsules
DrugParticipants will be treated for a maximum of 24 months
Safety - Adverse events (AE) will be compared between active and placebo arm
1. Proportion of AEs in the Ixazomib versus placebo arm in subjects with Relapsing Remitting Multiple Sclerosis (RRMS) 2. Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in subjects with RRMS 3. Proportion of AEs in the Ixazomib versus placebo arm in subjects with progressive MS 4. Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in subjects with progressive MS 5. Proportion of AEs in the Ixazomib versus placebo arm in all subjects (subjects with RRMS and subjects with progressive MS) 6. Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in all subjects (subjects with RRMS and subjects with progressive MS)
Efficacy - the proportion of OCB IgG negative subjects will be compared between active and placebo arm
1. Proportion of all subjects (Relapsing Remitting Multiple Sclerosis and progressive Multiple Sclerosis subjects) negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months 2. Proportion of subjects negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months in subjects with Relapsing Remitting Multiple Sclerosis (RRMS) 3. Proportion of subjects negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months in subjects with progressive Multiple Sclerosis
Magnetic Resonance Imaging (MRI)
Change in T2 lesion load and gadolinium enhancing lesions on brain MRI with Ixazomib versus placebo arm at 24 months
Change In Expanded Disability Status Scale (EDSS) with Ixazomib versus placebo arm at 24 months. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist
Change in EDSS with ixazomib versus placebo at 24 months.
Exploratory endpoint - IgG FLC
a. Proportion of all subjects who show reduction in total levels of Immunoglobulin G Free Light Chain (IgG FLC) in Cerebrospinal Fluid (CSF) at 24 months in the Ixazomib versus placebo arm.
Exploratory endpoint - CD19
b. Proportion of all subjects who show change in levels of Cluster of Differentiation antigen 19 (CD 19) at 24 months in the Ixazomib versus placebo arm.
Exploratory endpoint - soluble CD 138
c. Proportion of all subjects who show change in levels of soluble CD 138 at 24 months in the Ixazomib versus placebo arm
Exploratory endpoint - CD 27
d. Proportion of all subjects who show change in levels of soluble CD 27 at 24 months in the Ixazomib versus placebo arm
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Queen Mary University of London
Lead sponsor
Takeda Pharmaceuticals International, Inc.
Collaborator
