Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis: A Phase 1b Randomised, Double-blind, Placebo-controlled Trial.
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.
• \- Each participant must meet all of the following inclusion criteria to be enrolled in the study:
• Male and female patients 18 to 65 years old at screening
• Must have a diagnosis of MS, and:
‣ 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
• OCB positive CSF either from a previous CSF analysis or from the screening CSF analysis
• Able and willing to give written informed consent and comply with protocol requirements with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Agree to the use of effective contraception as follows:
• Female patients must:
⁃ Be postmenopausal for at least 1 year before the screening visit (postmenopausal status confirmed by serum Follicle Stimulating Hormone (FSH) and oestrogen levels at screening or from a historical sample), OR
⁃ Surgically sterile, OR
⁃ If they are of childbearing potential, must agree to practice two effective methods of contraception concurrently from the time of signing the informed consent form until 90 days after the last dose of study drug, OR
⁃ Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception
• Male patients must:
⁃ Even if surgically sterilized (post-vasectomy with documentation of azoospermia), agree to practice effective barrier contraception during the entire study treatment period and through to 90 days after the last dose of study drug, OR
⁃ Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception
• Clinical laboratory values:
∙ Absolute neutrophil count (ANC) ≥ 1 x 109/L
‣ Platelet count ≥ 100 x 109/L
‣ Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN)
‣ Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3 × ULN.
‣ Calculated creatinine clearance ≥ 30 mL/min