ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis

• Status: Not yet recruiting
• Trial end date: 2024-07-04
• Target enrollment: 0
• Participant gender: All

Summary

MS is a chronic inflammatory and degenerative disease of the central nervous system (CNS) affecting more than 120,000 people in the UK.and 2.5 million people worldwide.

Without disease modifying treatment (DMT),the majority of people with MS (pwMS) will develop significant disability within 10 years of onset, and 50% will require wheelchair assistance within 20 years. convenient, highly effective and CNS penetrant DMT for patients with relapsing multiple sclerosis (pwRMS) administered in short (8-10 days/year over 2 years) treatment courses.

It effectively depletes B cells, particularly Memory B cells, a likely key mechanism of disease control in MS. Cladribine is the investigational product in this study as it not currently used to treat patients with an EDSS of 6.5 - 8.5. This is a multi-centre, randomised double-blind placebo-controlled phase IIb to test cladribine tablets (MAVENCLAD®) (3.5mg/kg over 24 months) for safety, efficacy, and cost effectiveness, and to advance mechanistic understanding of its action in people with advanced MS (pwAMS).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen Mary University of London
• Collaborators: The Leeds Teaching Hospitals NHS Trust; University College, London; University of Edinburgh; University of Leeds; University of Plymouth
• Treatments: Cladribine

Criteria

Inclusion Criteria:

1. pwAMS aged 18+ years with an EDSS of 6.5-8.5 (inclusive)

2. History of bowel cancer screening for men and women and cervical and breast cancer screening for women as per NHS recommended guidelines. https://www.nhs.uk/conditions/nhs-screening/

3. Ability to complete the 9HPT with either upper limb within 180 seconds. The average score of both attempts for each hand should be used to assess eligibility.

4. Confirmation of MS diagnosis according to the McDonald Criteria (2017) Thompson et al. 2018)

5. In the judgement of the investigator, evidence of deterioration of upper limb function during the 2 years running up to the screening date

Exclusion Criteria:

1. Participants with known hypersensitivity to Cladribine of any grade (as per CTCAE grading system) should be excluded

2. Any uncontrolled diabetes, arterial hypertension and hypercholesterolaemia as determined by PI or delegated sub-investigator

3. A history of stroke, deep vein or sinus venous thrombosis and/or myocardial infarction

4. Moderate to severe renal impairment (creatinine clearance <60 ml/min)

5. Moderate to severe hepatic impairment (Child-Pugh score >6)

6. Significant comorbidity, e.g. cardiac failure, renal failure, malignancy, or other health condition that in the view of the PI or delegated sub-investigator precludes participation

7. Pregnancy including planning to father a child or breastfeeding

8. Body weight less <40kg

9. Unwillingness to use effective contraception throughout the trial period until at least six months after the last administration of IMP. This is not applicable for post-menopausal women

10. Acute infection

11. Infection with Human Immunodeficiency Virus 1 and/or 2

12. Active chronic infection (Syphilis, Tuberculosis, Hepatitis)

13. Precancerous condition or previous diagnosis of cancer

14. Total lymphocyte count <1.0*109/mL

15. Seronegativity for varicella zoster IgG, rubella, measles, mumps. Potential participants who fall in this category may undergo vaccination and can be screened (again) once full course has been completed.

16. Relapse within six months before screening

17. Inability to complete an MRI (contraindications for MRI, including but not limited to, MRI non- compatible pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry in the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, severe anxiety or claustrophobia etc.) or contraindication to Gd administration.

18. Treatment with steroids due to MS relapse/progression within three months of screening.

pwAMS who fall in this category may undergo a further screening visit once the three months' window has expired and may be included if no steroid treatment has been administered in the intervening period.

19. Treatment with any interferon-beta, glatiramer acetate, teriflunomide or dimethyl-fumarate within three months before screening.

20. Treatment with natalizumab, fingolimod, siponimod, ponesimod, ozanimod (or other Sphingosine-1-phosphate receptor modulators) within three months of screening.

21. Treatment with azathioprine, methotrexate, or cyclosporine within six months before screening.

22. pwAMS treated with teriflunomide will need to undergo accelerated elimination of the compound before being considered (Research and Case Medical Research 2019).

23. Treatment with haematopoietic stem cell transplantation (HSCT), mitoxantrone, cyclophosphamide, cladribine, alemtuzumab or another B cell depleting compound, such as rituximab, ocrelizumab, ublitiuximab, ofatumumab, or biosimilars, unless the participant concerned has a memory B cell level of ≥20% of the CD19+ population in the peripheral blood. Such a level would normally not be expected earlier than a minimum of six months after the last drug administration. Participants who underwent such treatment will therefore have to be tested for their CD19+/CD27+ memory B cell level at screening.

24. Treatment with fampridine: If they are already on treatment for at least six months, participants should continue throughout the trial. However, starting continuous fampridine treatment after signing the consent sheet will lead to exclusion from treatment with IMP/placebo.

25. Concurrent participation or previous participation within the last 6 months in another clinical trial of an IMP or medical device.

26. Unable to swallow tablets