Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis (CLOCK-MS)

The Washington University

Status and phase: Active, not recruiting; Phase 4

Conditions: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Treatments: Drug: Cladribine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03963375

MS700568_0049-201906092

Details and patient eligibility

About

The purpose of this study is to better understand the mechanism of action (MoA) of cladribine tablets by exploring the effect on central nervous system (CNS) and blood biomarkers relevant in the relapsing forms of multiple sclerosis (RMS; to include relapsing-remitting MS [RRMS] or active secondary progressive MS).

Full description

This is an open label, randomized, multicenter collaborative research Phase 4 biomarker study, designed to generate hypotheses to better understand the MoA of cladribine tablets in RMS (to include RRMS or active secondary progressive MS). The study is designed to generate hypotheses regarding the impact and relevance of cladribine tablet activity in the CNS by assessing the cerebrospinal (CSF) levels of lymphocyte subsets, other immune cells, neuronal injury markers and soluble immunological markers in study participants with RMS before and during treatment with cladribine tablets, and the association of these CSF markers with corresponding blood markers and with clinical outcomes.

Enrollment: 47 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Have a relapsing form of multiple sclerosis (RMS; to include RRMS or active secondary progressive MS)
2. Are willing and able to receive at least 2 lumbar punctures
3. Have an EDSS of 0 to ≤ 5.5 during the screening period
4. Had at least 1 relapse or 1 gadolinium-enhancing or 1 new or enlarged T2 lesion in the last 12 months
5. Have absolute lymphocyte count (ALC) within normal range of the local laboratory or assessed as normal by the investigator within the 3 week screening period and meet all other eligibility criteria for cladribine tablet treatment
6. Capable of giving signed informed consent

Exclusion criteria

1. Have any contraindication for lumbar puncture
2. Have current malignancy
3. Are infected with human immunodeficiency virus (HIV)
4. Have active chronic infections (e.g. hepatitis or tuberculosis)
5. Have signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML) in MRI
6. Have history of hypersensitivity to cladribine or any of the excipients listed in the cladribine tablets US Prescribing Information
7. Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform a MRI
8. Have any other comorbid conditions that preclude participation
9. Have been previously treated with cladribine
10. Have previously been treated with ocrelizumab, alemtuzumab, rituximab, or daclizumab
11. Have received treatment with natalizumab during the last 6 months
12. Are currently receiving immunosuppressive or myelosuppressive therapy, e.g., methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic treatment with systemic corticosteroids
13. Have received treatment with immunosuppressive or myelosuppressive therapy during the last 6 months
14. Have received chronic treatment with systemic corticosteroids during the last 4 weeks
15. Have moderate or severe hepatic impairment (Child-Pugh score >6)
16. Have moderate or severe renal impairment (creatinine clearance <60 mL per minute)
17. Are pregnant or unwilling or unable to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course
18. Are intending to breastfeed on a cladribine tablet treatment day and/or during the 10 days after the last cladribine tablet dose.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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47 participants in 4 patient groups

Group 1: LP at Baseline and Week 5

Other group

Description:

Group 1: LP at Baseline and end of Week 5. Week 5 is the optimal time point for assessing cladribine concentrations in CSF

Treatment:

Drug: Cladribine

Group 2: LP at Baseline and Week 10

Other group

Description:

Group 2: LP at Baseline and end of Week 10. Week 10 is the expected "nadir" time for lymphocyte and monocyte levels in CSF

Treatment:

Drug: Cladribine

Group 3: LP at Baseline and End of Year 1

Other group

Description:

Group 3: LP at Baseline and end of Year 1. To assess if cladribine effects on CSF markers are maintained at the end of the first treatment cycle

Treatment:

Drug: Cladribine

Group 4: LP at Baseline and End of Year 2

Other group

Description:

Group 4: LP at Baseline and end of Year 2. To assess if cladribine effects on CSF markers are maintained at the end of the last treatment cycle

Treatment:

Drug: Cladribine