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出境医 / 临床实验 / Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis (CLOCK-MS)
Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis (CLOCK-MS)
Study Description
Brief Summary:
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting | Drug: Cladribine | Phase 4 |
Detailed Description:
This will be 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.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 50 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | All patients will receive cladribine treatment per standard of care. Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures (LP) according to 1 of the 4 following schedules: Group 1: Baseline and end of Week 5; Group 2: Baseline and end of Week 10; Group 3: Baseline and end of Year 1; Group 4: Baseline and end of Year 2 . Patients in Groups 1-3 will have the option to undergo a third LP at the end of Year 2. |
| Masking: | None (Open Label) |
| Primary Purpose: | Basic Science |
| Official Title: | Cladribine Tablets: Collaborative Study to Evaluate the Impact On Central Nervous System Biomarkers in Multiple Sclerosis |
| Actual Study Start Date : | October 28, 2019 |
| Estimated Primary Completion Date : | June 2023 |
| Estimated Study Completion Date : | June 2023 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Group 1: LP at Baseline and Week 5
Group 1: LP at Baseline and end of Week 5. Week 5 is the optimal time point for assessing cladribine concentrations in CSF
|
Drug: Cladribine
All participants will receive cladribine 10 mg tablets at a cumulative dosage of 3.5 mg/kg divided into 2 treatment courses as per the United States Prescribing Information (USPI) (1.75 mg/kg per treatment course; Year 1 and Year 2 treatment). Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures at specific time points during the treatment cycle.
|
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Group 2: LP at Baseline and Week 10
Group 2: LP at Baseline and end of Week 10. Week 10 is the expected "nadir" time for lymphocyte and monocyte levels in CSF
|
Drug: Cladribine
All participants will receive cladribine 10 mg tablets at a cumulative dosage of 3.5 mg/kg divided into 2 treatment courses as per the United States Prescribing Information (USPI) (1.75 mg/kg per treatment course; Year 1 and Year 2 treatment). Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures at specific time points during the treatment cycle.
|
|
Group 3: LP at Baseline and End of Year 1
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
|
Drug: Cladribine
All participants will receive cladribine 10 mg tablets at a cumulative dosage of 3.5 mg/kg divided into 2 treatment courses as per the United States Prescribing Information (USPI) (1.75 mg/kg per treatment course; Year 1 and Year 2 treatment). Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures at specific time points during the treatment cycle.
|
|
Group 4: LP at Baseline and End of Year 2
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
|
Drug: Cladribine
All participants will receive cladribine 10 mg tablets at a cumulative dosage of 3.5 mg/kg divided into 2 treatment courses as per the United States Prescribing Information (USPI) (1.75 mg/kg per treatment course; Year 1 and Year 2 treatment). Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures at specific time points during the treatment cycle.
|
Outcome Measures
Primary Outcome Measures :
- Changes in the CSF levels of lymphocyte subtypes and markers of neuronal injury during treatment with cladribine tablets in patients with RMS [ Time Frame: 5 weeks, 10 weeks, 1 year, or 2 years ]Change in CSF levels of CD3+ T lymphocytes, CD19+ B lymphocytes, and NfL in the CSF from baseline to second LP using quality-controlled flow cytometry and assays
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Have a relapsing form of multiple sclerosis (RMS; to include RRMS or active secondary progressive MS)
- Have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS
- Are willing and able to receive at least 2 lumbar punctures
- Capable of giving signed informed consent
Exclusion Criteria:
- Have any contraindication for lumbar puncture or any other comorbid conditions that preclude participation
- Are infected with human immunodeficiency virus (HIV)
- Have active chronic infections (e.g. hepatitis or tuberculosis)
- Have been previously treated with cladribine
- Have previously been treated with ocrelizumab, alemtuzumab, rituximab, or daclizumab
- Have received treatment with natalizumab during the last 6 months
- Are currently receiving immunosuppressive or myelosuppressive therapy, e.g., methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic treatment with systemic corticosteroids
- Have moderate or severe hepatic or renal impairment
- 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
- Are intending to breastfeed on a cladribine tablet treatment day and/or during the 10 days after the last cladribine tablet dose.
Contacts and Locations
Contacts
| Contact: Gregory F Wu, MD, PhD | 314-362-3293 | gfwu@wustl.edu | |
| Contact: Dana Perantie | dperantie@wustl.edu |
Locations
| United States, Missouri | |
| Washington University School of Medicine | Recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| Contact: Gregory Wu, MD, PhD 314-362-3293 clockms@wustl.edu | |
| Contact: Dana Perantie dperantie@wustl.edu | |
| Principal Investigator: Gregory Wu, MD, PhD | |
| Sub-Investigator: Anne Cross, MD | |
Sponsors and Collaborators
Washington University School of Medicine
EMD Serono
Investigators
| Principal Investigator: | Gregory Wu | Washington University School of Medicine |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 23, 2019 | ||||||||
| First Posted Date ICMJE | May 24, 2019 | ||||||||
| Last Update Posted Date | May 22, 2020 | ||||||||
| Actual Study Start Date ICMJE | October 28, 2019 | ||||||||
| Estimated Primary Completion Date | June 2023 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Changes in the CSF levels of lymphocyte subtypes and markers of neuronal injury during treatment with cladribine tablets in patients with RMS [ Time Frame: 5 weeks, 10 weeks, 1 year, or 2 years ] Change in CSF levels of CD3+ T lymphocytes, CD19+ B lymphocytes, and NfL in the CSF from baseline to second LP using quality-controlled flow cytometry and assays
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis | ||||||||
| Official Title ICMJE | Cladribine Tablets: Collaborative Study to Evaluate the Impact On Central Nervous System Biomarkers in Multiple Sclerosis | ||||||||
| Brief Summary | 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). | ||||||||
| Detailed Description | This will be 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. | ||||||||
| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 4 | ||||||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: All patients will receive cladribine treatment per standard of care. Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures (LP) according to 1 of the 4 following schedules: Group 1: Baseline and end of Week 5; Group 2: Baseline and end of Week 10; Group 3: Baseline and end of Year 1; Group 4: Baseline and end of Year 2 . Patients in Groups 1-3 will have the option to undergo a third LP at the end of Year 2. Masking: None (Open Label)Primary Purpose: Basic Science |
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| Condition ICMJE |
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| Intervention ICMJE | Drug: Cladribine
All participants will receive cladribine 10 mg tablets at a cumulative dosage of 3.5 mg/kg divided into 2 treatment courses as per the United States Prescribing Information (USPI) (1.75 mg/kg per treatment course; Year 1 and Year 2 treatment). Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures at specific time points during the treatment cycle.
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
50 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | June 2023 | ||||||||
| Estimated Primary Completion Date | June 2023 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 65 Years (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | United States | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03963375 | ||||||||
| Other Study ID Numbers ICMJE | MS700568_0049 | ||||||||
| Has Data Monitoring Committee | Yes | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Washington University School of Medicine | ||||||||
| Study Sponsor ICMJE | Washington University School of Medicine | ||||||||
| Collaborators ICMJE | EMD Serono | ||||||||
| Investigators ICMJE |
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| PRS Account | Washington University School of Medicine | ||||||||
| Verification Date | May 2020 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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