CLOCK-MS
What it found
The main measure showed a statistically significant benefit.
| Measure | Estimate | 95% CI | p |
|---|---|---|---|
| Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 10 | 0.01 | ||
| Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 10 | 0.01 | ||
| Change in CD19+ B Cells % From Baseline to Week 10 | 0.01 | ||
| Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 1 | 0.02 | ||
| Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 1 | 0.04 | ||
| Change in CD3+ T Cells % From Baseline to Year 1 | 0.04 | ||
| Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 1 | 0.08 | ||
| Change in CD3+ T Cells % From Baseline to Week 10 | 0.08 | ||
| Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 10 | 0.11 | ||
| Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 5 | 0.21 | ||
| Change in CD19+ B Cells % From Baseline to Year 1 | 0.34 | ||
| Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 2 | 0.50 | ||
| Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 5 | 0.72 | ||
| Change in CD3+ T Cells % From Baseline to Week 5 | 0.72 | ||
| Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 5 | 0.88 | ||
| Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 2 | 0.91 | ||
| Change in CD19+ B Cells % From Baseline to Year 2 | 0.91 | ||
| Change in CD19+ B Cells % From Baseline to Week 5 | 0.96 | ||
| Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 2 | 0.97 | ||
| Change in CD3+ T Cells % From Baseline to Year 2 | 0.97 |
Statistical analysis as posted on ClinicalTrials.gov.
What was tested
Treatment tested
- Cladribine
DNA inhibitor
Results by group
Change in CD3+ T Cells % From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 5 | 0.7 Percentage of CD3+ T cells | -5.8–10.5 | 8 |
p = 0.72
Change in CD3+ T Cells % From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 10 | -2.3 Percentage of CD3+ T cells | -8.6–-0.4 | 11 |
p = 0.08
Change in CD3+ T Cells % From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 1 | -7.6 Percentage of CD3+ T cells | -13.4–-0.5 | 12 |
p = 0.04
Change in CD3+ T Cells % From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 2 | 0.7 Percentage of CD3+ T cells | -6.2–31.1 | 4 |
p = 0.97
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 5
Baseline to Week 5
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 5 | -146.6 Cells/mL | -348.6–-28.3 | 8 |
p = 0.21
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 10 | -201.9 Cells/mL | -1775.1–-106.8 | 11 |
p = 0.01
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 1 | -121.9 Cells/mL | -445.5–-46.9 | 12 |
p = 0.02
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 2 | -0.3 Cells/mL | -1116.2–401.4 | 4 |
p = 0.97
Change in CD19+ B Cells % From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 5 | 0.0 Percentage of CD19+ B cells | -0.5–0.6 | 8 |
p = 0.96
Change in CD19+ B Cells % From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 10 | -1.8 Percentage of CD19+ B cells | -2.1–-0.6 | 11 |
p = 0.01
Change in CD19+ B Cells % From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 1 | -0.5 Percentage of CD19+ B cells | -1.3–0 | 12 |
p = 0.34
Change in CD19+ B Cells % From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 2 | 0.4 Percentage of CD19+ B cells | -0.7–1.5 | 4 |
p = 0.91
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 5 | -0.6 Cells/mL | -1.5–0.8 | 8 |
p = 0.72
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 10 | -11.8 Cells/mL | -62.6–-5.1 | 11 |
p = 0.01
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 1 | -4.3 Cells/mL | -14.2–0.4 | 12 |
p = 0.08
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 2 | -0.9 Cells/mL | -30.6–8.5 | 4 |
p = 0.91
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 5 | 7.0 pg/mL | -310–260 | 7 |
p = 0.88
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Week 10 | -91.0 pg/mL | -512–9 | 11 |
p = 0.11
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 1 | -294.0 pg/mL | -991–-129 | 11 |
p = 0.04
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Year 2 | -299.0 pg/mL | -609–-4 | 5 |
p = 0.50
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Group 1: LP at Baseline and Week 5 | 9 | 0 (0.0%) | 0 |
| Group 2: LP at Baseline and Week 10 | 15 | 1 (6.7%) | 0 |
| Group 3: LP at Baseline and End of Year 1 | 16 | 0 (0.0%) | 0 |
| Group 4: LP at Baseline and End of Year 2 | 7 | 0 (0.0%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Change in CD3+ T Cells % From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells % From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells % From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells % From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 5
Baseline to Week 5
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells % From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells % From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells % From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells % From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
Blood or spinal fluid markersImmune responseChange in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
Blood or spinal fluid markersImmune responseChange in the Neurofilament Light Chain (NfL) Level From Baseline to Week 5
Baseline to Week 5 (5 weeks after first cladribine dose)
Blood or spinal fluid markersChange in the Neurofilament Light Chain (NfL) Level From Baseline to Week 10
Baseline to Week 10 (10 weeks after first cladribine dose)
Blood or spinal fluid markersChange in the Neurofilament Light Chain (NfL) Level From Baseline to Year 1
Baseline to Year 1 (45 weeks after first cladribine dose)
Blood or spinal fluid markersChange in the Neurofilament Light Chain (NfL) Level From Baseline to Year 2
Baseline to Year 2 (45 weeks after last cladribine dose)
Blood or spinal fluid markers
Who could take part
Relapsing and progressive · 18 to 65
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.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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).
Papers
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Related trials
History
Started
Oct 2019
Main results due
May 2025
Finished
May 2025
Results posted
Jul 2026
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