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

Primary Purpose

Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Status

Active

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Cladribine

About this trial

This is an interventional basic science trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have a relapsing form of multiple sclerosis (RMS; to include RRMS or active secondary progressive MS)
Are willing and able to receive at least 2 lumbar punctures
Have an EDSS of 0 to ≤ 5.5 during the screening period
Had at least 1 relapse or 1 gadolinium-enhancing or 1 new or enlarged T2 lesion in the last 12 months
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
Capable of giving signed informed consent

Exclusion Criteria:

Have any contraindication for lumbar puncture
Have current malignancy
Are infected with human immunodeficiency virus (HIV)
Have active chronic infections (e.g. hepatitis or tuberculosis)
Have signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML) in MRI
Have history of hypersensitivity to cladribine or any of the excipients listed in the cladribine tablets US Prescribing Information
Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform a MRI
Have any other comorbid conditions that preclude participation
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 received treatment with immunosuppressive or myelosuppressive therapy during the last 6 months
Have received chronic treatment with systemic corticosteroids during the last 4 weeks
Have moderate or severe hepatic impairment (Child-Pugh score >6)
Have moderate or severe renal impairment (creatinine clearance <60 mL per minute)
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.

Sites / Locations

Washington University School of Medicine
Oklahoma Medical Research Foundation
University of Pennsylvania
University of Texas Southwestern Medical Center
Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Arm Label

Group 1: LP at Baseline and Week 5

Group 2: LP at Baseline and Week 10

Group 3: LP at Baseline and End of Year 1

Group 4: LP at Baseline and End of Year 2

Arm Description

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

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

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

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

Outcomes

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03963375

First Posted

May 23, 2019

Last Updated

July 10, 2023

Sponsor

Washington University School of Medicine

Collaborators

EMD Serono

1. Study Identification

Unique Protocol Identification Number

NCT03963375

Brief Title

Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis

Acronym

CLOCK-MS

Official Title

Cladribine Tablets: Collaborative Study to Evaluate the Impact On Central Nervous System Biomarkers in Multiple Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 28, 2019 (Actual)

Primary Completion Date

May 30, 2025 (Anticipated)

Study Completion Date

May 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

Collaborators

EMD Serono

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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).

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: LP at Baseline and Week 5

Arm Type

Other

Arm Description

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

Arm Title

Group 2: LP at Baseline and Week 10

Arm Type

Other

Arm 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

Arm Title

Group 3: LP at Baseline and End of Year 1

Arm Type

Other

Arm 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

Arm Title

Group 4: LP at Baseline and End of Year 2

Arm Type

Other

Arm 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

Intervention Type

Drug

Intervention Name(s)

Cladribine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Changes in the CSF levels of lymphocyte subtypes and markers of neuronal injury during treatment with cladribine tablets in patients with RMS

Description

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

Time Frame

5 weeks, 10 weeks, 1 year, or 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have a relapsing form of multiple sclerosis (RMS; to include RRMS or active secondary progressive MS) Are willing and able to receive at least 2 lumbar punctures Have an EDSS of 0 to ≤ 5.5 during the screening period Had at least 1 relapse or 1 gadolinium-enhancing or 1 new or enlarged T2 lesion in the last 12 months 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 Capable of giving signed informed consent Exclusion Criteria: Have any contraindication for lumbar puncture Have current malignancy Are infected with human immunodeficiency virus (HIV) Have active chronic infections (e.g. hepatitis or tuberculosis) Have signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML) in MRI Have history of hypersensitivity to cladribine or any of the excipients listed in the cladribine tablets US Prescribing Information Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform a MRI Have any other comorbid conditions that preclude participation 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 received treatment with immunosuppressive or myelosuppressive therapy during the last 6 months Have received chronic treatment with systemic corticosteroids during the last 4 weeks Have moderate or severe hepatic impairment (Child-Pugh score >6) Have moderate or severe renal impairment (creatinine clearance <60 mL per minute) 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gregory Wu

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Oklahoma Medical Research Foundation

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Facility Name

Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis

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