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Multiple SclerosisPhase 4NCT04178005

Cladribine Tablets After Treatment With Natalizumab (CLADRINA)

A Phase 4 study testing Cladribine in people with Multiple Sclerosis, run by University of Texas Southwestern Medical Center at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to generate hypotheses regarding the safety, efficacy, and immunological impact of cladribine tablets after treatment with natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (active SPMS). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Cladribine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
19 Feb 2020to Dec 2026
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients who meet the following inclusion criteria will be eligible for enrollment in the study:
  • Age between 18 and 60 years, inclusive.
  • Diagnosis of relapsing forms of MS, to include RRMS and active SPMS, diagnosed with McDonald Criteria 2005, 2010, and/or 2017 (1-3)
  • EDSS 0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).
  • Has had a minimum of 12 months of continuous natalizumab therapy (300 mg/d), including patients receiving extended interval dosing of natalizumab (e.g., less frequently than every-4-week infusion).
  • Negative history for any relapses at least 28 days prior to enrollment.
Show all 12Show fewer
  • Weighing between 40 kilograms or more.
  • Female subjects of childbearing potential must use effective methods of contraception to prevent pregnancy for 4 weeks before initiation of cladribine tablets and must agree to continue to practice adequate contraception for at least 6 months after the last dose. Women using systemically acting hormonal contraceptives should add a barrier method during cladribine treatment and for at least 4 weeks after the last dose in each treatment year.
  • Female subjects must not be pregnant; female subjects must not be lactating or breast-feeding at least 10 days after the last dose.
  • Male subjects must be willing to use a condom during dosing and for six months after the last dose. Alternatively, their female partner must use another form of contraception (such as an intra-uterine device [IUD], barrier method with spermicide, or hormonal contraceptive [e.g., implant, injectable, patch or oral]) during dosing and for six months after last dose.
  • Understands and is capable of following through with study protocol requirements and assessments.
  • Willing to provide voluntary and informed consent based on the Health Insurance Portability and Accountability Act (HIPPA).

Who cannot join

  • Patients who meet any of the following exclusion criteria will not be eligible for enrollment in the study:
  • Natalizumab failure based on clinician's discretion.
  • Not active progressive MS (4).
  • A diagnosis of PML or any suspicion of PML.
  • A diagnosis of Clinically Isolated Syndrome
  • Known hypersensitivity to cladribine.
Show all 20Show fewer
  • Any prior exposure to cladribine.
  • Lymphocyte count not within normal limits of the local, hospital laboratory.
  • Previous or current exposure to mitoxantrone, azathioprine, methotrexate, cyclophosphamide, myelosuppressive treatments, total lymphoid irradiation.
  • Receiving oral or systemic corticosteroid treatments within the 28 days prior to enrollment.
  • Receiving cytokine base treatment, Intra Venous Immuno Globulin (IVIG) or Plasma pheresis, 3 months prior to enrollment in the study.
  • Having platelet count or neutrophil count below the lower limit of the normal range within the 28 days prior to enrollment in the study.
  • Positive for HIV, or positive hepatitis C antibody test or hepatitis B surface antigen test and/or core antibody test for IgG and/or IgM.
  • History of tuberculosis (TB), presence of active tuberculosis, or latent tuberculosis as detected by local standard of practice like imaging (e.g., chest X-ray, chest CT scan, MRI) and/or positive QuantiFERON-TB Gold test and/or skin test and/or clinical examination or has had latent TB disease at any time in the past.
  • Immunocompromised subjects, including subjects currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids.
  • Active malignancy or history of malignancy.
  • Received a live vaccine within 6 weeks prior to cladribine tablet administration or intends to receive a live vaccination during the trial. After the last dose of cladribine tablets, the subject should avoid live vaccine as long as the subject's white blood cell counts are not within normal limits.
  • Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform an MRI.
  • Has any renal condition that would preclude the administration of gadolinium (e.g. acute or chronic severe renal insufficiency (GFR < 30 mL/min/1.73m2)
  • -

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • UT Southwestern Medical center

    Dallas, Texas, 75390

  • College Park Family Care Center Physicians Group

    Overland Park, Kansas, 66212

Other trials in United States

About this study

The purpose of this study is to generate hypotheses regarding the safety, efficacy, and immunological impact of cladribine tablets after treatment with natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (active SPMS).

Read the detailed description

This will be an open label, single arm, multicenter, collaborative phase 4 research study, designed to generate hypotheses regarding the transition to cladribine tablets after treatment with natalizumab in patients with relapsing forms of multiple sclerosis MS, to include relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS).

The total duration of this interventional study will be 2 years, but patients who require additional time (up to 6 months) for recovery of Absolute lymphocyte count (ALC) to 800 cells/ul prior to the second treatment course will be followed for up to 6 additional months in order to have a full second year of follow up after initiation of the second year's treatment course (for a total study duration of up to 30 months in some patients). A total of 40 study participants with relapsing forms of MS, to include RRMS and active SPMS, who meet the criteria for treatment with cladribine tablets as per the approved United States Prescribing Information (USPI) are planned to be enrolled at up to three centers in the United States. All study participants will receive treatment with cladribine 10 mg tablets during year 1 and year 2 according to the approved USPI (EMD Serono, 2019). Cladribine 10 mg tablets will be provided as commercial material. Treatment with cladribine tablets is intended to be initiated approximately 14 days after the last infusion of natalizumab (e.g., a 14-day "washout"), with a maximum permissible washout period of no more than four weeks.

After successful completion of the study, all participants in CLADRINA will be offered to participate in the CLADRINA 2-Year Extension study. During this extension trial, there will be no intervention. Patient will be followed for an additional 24 months, and their clinical and paraclinical disease activity will be assessed through neurological examinations, EDSS scores, brain MRI, and biological markers.

Being tested
Cladribine
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CladribineDrug

    Also called Mavenclad

    All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI

Study groups in NCT04178005
Study groupRoleWhat they receive
CladribineOtherAll study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI. Each treatment course is divided into 2 treatment cycles: * Administration of first treatment course (year 1 treatment): * First cycle: Starts on Day 1 of the study * Second cycle: Administered 23 to 27 days after the last dose of first cycle. * Administration of second treatment course (year 2 treatment): * First cycle: Administered at least 43 weeks after the last dose of year 1 treatment * Second cycle: Administered 23 to 27 days after the last dose of first cycle of year 2 treatment. The cycle dosage will be administered as 1 or 2 cladribine 10 mg tablets daily over 4 or 5 consecutive days.
Receives: Drug: Cladribine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute and percent change of T cells, B cells, DC subset and NfL levels in blood.

    The absolute and percent change from baseline will be presented for each time point for CD3+ T lymphocytes, CD19+ B lymphocytes, CD11c+ DC subsets, NfL levels in blood, with a two-sided 95% CI and p value. As these data are not expected to be normally distributed, the nonparametric Wilcoxon signed rank test will be used to compare each biomarker at baseline and during treatment. Spearman rank correlations will be used to examine the relationship between biomarkers and clinical/safety endpoints.

    Measured: 24 months

Secondary outcomes (1)

  1. Annualized Relapse Rate (ARR)

    The ARR over the 12- and 24-month periods will be presented, accompanied by the respective 95% CIs. The proportion (and 95% CI) of participants experiencing a relapse over the 12 month and 24-month periods will also be presented.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Nov 2019
  2. Study start19 Feb 2020
  3. Primary completion30 Aug 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04178005
Sponsor's protocol ID
STU 2019-1618
Status last verified
Dec 2025
First submitted
21 Nov 2019
Last updated
8 Dec 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hartung HP, Graf J, Aktas O, Mares J, Barnett MH. Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 - continuity and change. Curr Opin Neurol. 2019 Jun;32(3):327-337. doi: 10.1097/WCO.0000000000000699.

    PubMed 30985371

  • Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. doi: 10.1002/ana.20703.

    PubMed 16283615

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.

    PubMed 21387374

  • Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, Wolinsky JS, Balcer LJ, Banwell B, Barkhof F, Bebo B Jr, Calabresi PA, Clanet M, Comi G, Fox RJ, Freedman MS, Goodman AD, Inglese M, Kappos L, Kieseier BC, Lincoln JA, Lubetzki C, Miller AE, Montalban X, O'Connor PW, Petkau J, Pozzilli C, Rudick RA, Sormani MP, Stuve O, Waubant E, Polman CH. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278-86. doi: 10.1212/WNL.0000000000000560. Epub 2014 May 28.

    PubMed 24871874

  • Shirani A, Stuve O. Natalizumab for Multiple Sclerosis: A Case in Point for the Impact of Translational Neuroimmunology. J Immunol. 2017 Feb 15;198(4):1381-1386. doi: 10.4049/jimmunol.1601358.

    PubMed 28167648

  • Shirani A, Stuve O. Natalizumab: Perspectives from the Bench to Bedside. Cold Spring Harb Perspect Med. 2018 Dec 3;8(12):a029066. doi: 10.1101/cshperspect.a029066.

    PubMed 29500304

  • Stuve O, Marra CM, Jerome KR, Cook L, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Hemmer B, Monson NL, Racke MK. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol. 2006 May;59(5):743-7. doi: 10.1002/ana.20858.

    PubMed 16634029

  • Stuve O, Marra CM, Bar-Or A, Niino M, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Jerome KR, Cook L, Grand'Maison F, Hemmer B, Monson NL, Racke MK. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch Neurol. 2006 Oct;63(10):1383-7. doi: 10.1001/archneur.63.10.1383.

    PubMed 17030653

  • Stuve O, Cravens PD, Frohman EM, Phillips JT, Remington GM, von Geldern G, Cepok S, Singh MP, Tervaert JW, De Baets M, MacManus D, Miller DH, Radu EW, Cameron EM, Monson NL, Zhang S, Kim R, Hemmer B, Racke MK. Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology. 2009 Feb 3;72(5):396-401. doi: 10.1212/01.wnl.0000327341.89587.76. Epub 2008 Nov 5.

    PubMed 18987352

  • del Pilar Martin M, Cravens PD, Winger R, Frohman EM, Racke MK, Eagar TN, Zamvil SS, Weber MS, Hemmer B, Karandikar NJ, Kleinschmidt-DeMasters BK, Stuve O. Decrease in the numbers of dendritic cells and CD4+ T cells in cerebral perivascular spaces due to natalizumab. Arch Neurol. 2008 Dec;65(12):1596-603. doi: 10.1001/archneur.65.12.noc80051. Epub 2008 Oct 13.

    PubMed 18852339

  • Yao K, Gagnon S, Akhyani N, Williams E, Fotheringham J, Frohman E, Stuve O, Monson N, Racke MK, Jacobson S. Reactivation of human herpesvirus-6 in natalizumab treated multiple sclerosis patients. PLoS One. 2008 Apr 30;3(4):e2028. doi: 10.1371/journal.pone.0002028.

    PubMed 18446218

  • Stuve O, Bennett JL. Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri) in inflammatory diseases. CNS Drug Rev. 2007 Spring;13(1):79-95. doi: 10.1111/j.1527-3458.2007.00003.x.

    PubMed 17461891

  • Cutter GR, Stuve O. Does risk stratification decrease the risk of natalizumab-associated PML? Where is the evidence? Mult Scler. 2014 Sep;20(10):1304-5. doi: 10.1177/1352458514531843. Epub 2014 May 8.

    PubMed 24812045

  • Berger JR, Fox RJ. Erratum to: Reassessing the risk of natalizumab-associated PML. J Neurovirol. 2016 Aug;22(4):536-537. doi: 10.1007/s13365-016-0431-x. No abstract available.

    PubMed 27026534

  • Berger JR, Fox RJ. Reassessing the risk of natalizumab-associated PML. J Neurovirol. 2016 Aug;22(4):533-5. doi: 10.1007/s13365-016-0427-6. Epub 2016 Feb 3.

    PubMed 26843383

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cladribine in people with Multiple Sclerosis, run by University of Texas Southwestern Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute and percent change of T cells, B cells, DC subset and NfL levels in blood. (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04178005, which also lists 39 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.

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