OCTOPUS - Optimal Clinical Trials Platform for Progressive Multiple Sclerosis
Primary progressive multiple sclerosis and secondary progressive multiple sclerosis
Participants will be randomised at each site via the OCTOPUS eDC System, a centrally managed system hosted by MRC CTU, accessible to authorised members of the research teams at recruiting site using a web-based interface. Eligibility and consent will be verified before each participant is randomised and is then confirmed within the system at the time of randomisation. If participants are ineligible for an arm, they can be assessed for eligibility and randomised to other open arms. Participants will be allocated using an eDC system into one of the three arms in a 1:1:1 ratio utilising minimisation based on key prognostic factors and a random element. OCTOPUS is a blinded trial therefore all participants have the same dosing and assessment schedule. Following randomisation, participants will initially be asked to take the “low dose” of 2 capsules a day in the evening shortly after a meal (called the low dose) for 4 weeks. If the participant is tolerating this dose and they are happy to do so, they will then have their dosage increased to the high dose of 2 capsules twice a day shortly after meals (a total of 4 capsules). Participants will be asked to visit your study doctor at one month; have a telephone call at three months, and then another visit at six months. After this you will be asked to visit the hospital every 6 months for up to 5 years. Between the 6 monthly visits you will be asked to do a urine test and have a telephone call with the research nurse to report the result. At each visit to the hospital, participants will have the physical assessments to test the neurological system, and fill in questionnaires on pain, fatigue, mobility, and quality of life. Further tests will be done to check their progress and if they have any problems with the treatment. Depending on side effects and tolerability dose may be modified accordingly in accordance with the protocol.
Current key inclusion criteria as of 05/06/2026: CORE INCLUSION CRITERIA 1. Participants with a confirmed diagnosis of MS 2. A diagnosis of Secondary Progressive MS (SPMS) or Primary Progressive MS (PPMS). 3. Steady progression as assessed by the treating clinician, rather than relapse (as defined in protocol section 6.5.6), must be the major cause of increasing disability in the preceding 2 years. Progression can be evident from either an increase of at least 1 point if on the Expanded Disability Status Scale (EDSS) score <5.5, or an increase of at least 0.5 point if EDSS score ≥5.5, and/or clinical documentation of increasing disability 4. EDSS 4.0 – 8.0 (inclusive) as assessed at the time of randomisation by the assessor 1. Aged 25 - 70 years old inclusive on the day of randomisation 2. Adequate renal function at screening, defined as eGFR ≥60ml/min/1.73m2 (as per local method) 3. Normal liver function at screening consisting of all the following: a. Serum bilirubin <1.5 x ULN (except for participants with Gilbert’s disease, for whom the upper limit of serum bilirubin is 51.3 µmol/l or 3mg/dl) b. Either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x ULN; (it must be stated whether one or both tests were performed. Where both results are available, both must confirm eligibility) c. Alkaline phosphatase <3 x ULN 4. Must be able and willing to comply with the treatment and assessment schedule and requirements including being able to start trial treatment ≤ 2 weeks after randomisation. 5. Written informed consent provided 6. [Please note no longer core inclusion criteria in Analysis Stage 2 - Must have a QC approved (as defined in MRI guide) MRI ≤ 4 weeks before randomisation] 7. [Please note no longer core inclusion criteria in Analysis Stage 2 - Willing and able to have MRI scans in accordance with the assessment schedule and no contraindication to MRI (please refer to MRI Procedures and Protocol for further detail)] _____ Previo
Current key exclusion criteria as of 05/06/2026: CORE EXCLUSION CRITERIA 1. Relapse (as defined in protocol section 6.5.6) ≤ 12 weeks before randomisation 2. Significant comorbidity (as confirmed by treating clinician) that includes but not limited to the following: a. Cardiac failure (clinical diagnosis) b. Significant Respiratory comorbidity c. Renal failure d. Malignancy (except if in complete remission) – e.g. solid organ or haematological or melanoma e. Uncontrolled thyroid disease f. Significant non-MS neurological comorbidity g. Hepatic impairment 3. [Please note this number is no longer core exclusion criteria: moved to Metformin exclusion criteria only - Rare hereditary problems of galactose intolerance or glucose-galactose] 4. Active partial or total malabsorptive disease (e.g. coeliac disease) 5. Alcohol use disorder or illicit drug use within the last 5 years (excluding cannabis for symptomatic relief) 6. Female participants that are pregnant or breast-feeding. 7. Women of child-bearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception (see protocol Appendix 1) whilst on trial treatment and up to 12 weeks after the last dose of study drug. 8. Use of an investigational medicinal product or investigational medical device ≤ 26 weeks before randomisation. 9. Men with a partner of child-bearing potential unwilling to use an acceptable method of contraception during the trial and for 12 weeks after the last dose of trial treatment. 10. Male participants unwilling to desist from sperm donation during the trial and for 12 weeks after the last dose of trial treatment. 11. Been treated with steroids (intravenous and/or oral) for MS relapse or progression ≤ 12 weeks before randomisation* Note: Participants on steroids for another medical condition may be included in the trial provided the steroid prescription is not for any aspects of their MS. 12. Current or previous treatment with OCTOPUS IMPs ≤ 26 weeks before rand