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Multiple SclerosisPhase 4NCT04550455

A Prospective Biomarker Study in Active SPMS Subjects Treated With Cladribine Tablets

A Phase 4 study testing Cladribine Tablets in people with Multiple Sclerosis, run by Keith Edwards, M.D. at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to explore the concept that biomarker sensitivity will detect activity in Multiple Sclerosis (MS) subjects and allow appropriate change in treatment to prevent dysfunction. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Cladribine Tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
16 Sep 2020to Dec 2025
Phase
Phase 4
Are there results?
None posted in the registry

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 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female between 21 and 65 years old, inclusive.
  • Must be capable of understanding and providing written informed consent, including subject authorization under the health insurance portability and accountability act (HIPPA), prior to any study related procedures that are not part of routine medical care.
  • Has an EDSS score at the screening visit of 2.0 to 7.0 inclusive.
  • Have a diagnosis of clinically definite SPMS. (Lublin, 2014)
  • Are considered neurologically stable for > 30 days prior to both screening, baseline and week 48.
  • Must be otherwise healthy without confounding diseases.
Show all 14Show fewer
  • Subject has decided to pursue cladribine tablets as their disease modifying therapy (DMT) of choice, and have signed a study specific informed consent form.
  • Must be willing and physically able to comply with all required protocol visits and complete all assessments.
  • Must be willing to complete 2 years of routine clinic follow-ups after study completion as per cladribine tablets FDA guidelines.
  • Must have read the FDA approved patient labeling (medication guide) and be counseled, risk of teratogenicity, lactation, lymphopenia and other hematologic toxicity, infections, liver injury, hypersensitivity, cardiac failure and treatment handling and administration.
  • If female: must have a negative serum pregnancy test at screen and week 48 and a negative urine pregnancy test at baseline. All females must agree to notify us immediately if they have concern of possible pregnancy.
  • If female: be neither pregnant or breastfeeding, nor attempting to conceive AND
  • Use a highly effective method of contraception throughout the entire duration of the study and for 6 months (5 menstrual cycles) following completion of the last dose of study medication. As it is currently unknown whether cladribine tablets may reduce the effectiveness of systemically acting hormonal contraceptives, a barrier method of contraception should be implemented for the duration of the study.
  • If Male: must be willing to use contraception to avoid contributing to pregnancies 6 months following the last dose of study medication.

Who cannot join

  • Subjects with a diagnosis of a sub-type of MS other than PMS active (clinically definite SPMS)
  • Have MRI findings other than MS that are considered significant per the P.I.
  • Have a clinical condition or medical history noted as a contraindication as per the FDA/US package insert guidelines.
  • Have a history of chronic disease(s) of the immune system, other than MS or a known immunodeficiency syndrome.
  • Have comorbid conditions that preclude participation, including any condition that might increase brain biomarkers such as traumatic brain injury (TBI), meningitis, stroke, or drug abuse in the last 12 months or any other medical condition deemed significant for increased biomarkers by the investigator.
  • Have an active/acute infection (bacterial, viral, fungal, etc.) at the time of screen AND/OR baseline or within 4 weeks prior to or at the start of course 2 year 2 that would interfere with the safety of the study.
Show all 39Show fewer
  • Have a current or past significant history of poorly controlled diabetes mellitus, obesity (BMI over 35) or anorexia (BMI under 18), hypertension or hyperlipidemia as determined by the investigator.
  • Have a history or presence of malignancy other than basal cell epithelioma (BCE) or cervical cancer in-situ following a complete excision. Cancer that has been absent for more than 10 years and considered to be cured is allowed.
  • All standard cancer screening guidelines should be followed for subjects that are treated with cladribine tablets during the course of the study.
  • Known liver conditions including the following:
  • History or current hepatic impairment considered moderate or severe. Subjects with mild hepatic impairment can be considered at the investigator's discretion.
  • Current or known history of alcohol abuse
  • Chronic liver or biliary diseases
  • Total or conjugated bilirubin greater than the upper limit of normal range
  • Alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal range
  • Aspartate transaminase (AST/ aka SGOT) and/or an alanine transaminase (ALT/aka SGPT) greater than 2 times the upper limit of normal range.
  • Gamma-glutamyl-transferase (GGT) greater than 3 times the upper limit of normal.
  • History of or current renal Impairment that is considered moderate to severe. (creatinine clearance below 50 mL per minute)
  • Any other significant medical condition that in the opinion of the investigator that could potentially cause interference of complications of subject taking study Investigational Product (IP).
  • Have a contraindication to a lumbar puncture. (i.e. abnormal coagulation panel, skin infection at the location of Lumbar Puncture (LP), increased cranial pressure, etc.)
  • Any laboratory results at screen and/or prior to course 2 that are considered significant, such as but not limited to, abnormal lymphocyte count, positive hepatitis B and/or C screen, positive HIV test, etc. Any abnormal lab results must be approved by the investigator prior to initiating the first AND second course of IP therapy.
  • Have a lymphocyte count that is not at least 800 cells per microliter before initiating the second treatment course at week 48. If necessary, the second treatment course can be delayed as per FDA/US package insert guidelines.
  • Unable to undergo the required MRI scans for any reason, including claustrophobia and a history of hypersensitivity to Gd+.
  • Females who are pregnant, plan to become pregnant or who are breastfeeding during the study or plan on becoming pregnant or breastfeeding within 6 months of the last dose of cladribine tablets.
  • Males whose partner plans to become pregnant during the study or become pregnant within 6 months of the last dose of cladribine tablets.
  • Screening labs may be repeated in 2-6 weeks if an abnormality is felt to be due to a transient, reversible condition
  • Subjects that have previously been treated with cladribine in any dosing form (intravenous, subcutaneous, oral) are not allowed.
  • Subjects with a history of any of the following:
  • Prior alemtuzumab treatment
  • Prior or current investigational or non-FDA approved DMT or procedure
  • Prior or current stem cell transplant for any reason
  • Treatment with ocrelizumab or rituximab within 12 months of last dose to baseline
  • Treatment with natalizumab within 1 year of screen. If subject has a prior history of treatment with natalizumab, the subject must also be JCV (John Cunningham virus) negative or have JCV index of 0.5 or lower. A past JCV index over 0.5 is exclusionary.
  • Treatment with fingolimod, teriflunomide or dimethyl fumarate (DMF) within 4 weeks prior to baseline
  • Treatment with interferon(IFN) or glatiramer acetate(GA) within 4 weeks of baseline
  • Treatment with Intravenous immune globulin (IVIG) or plasmapheresis within 12 weeks prior to screening
  • Treatment with an immunosuppressant such as cyclophosphamide, mitoxantrone, azathioprine, mycophenolate within 3 years prior to screening.
  • Systemic corticosteroid within 2 weeks prior to screening. The screening period may be extended up to 4 weeks for patients who have used systemic corticosteroids but for a patient to be eligible for enrollment, no corticosteroids should be administered between screening and baseline
  • Treatment with concomitant drugs used for symptomatic treatment of spasticity or neuropathic pain, (i.e. baclofen, lorazepam, or gabapentin) as long as they have been stable dose for at least 30 days prior to screen. Medical Marijuana is allowed per investigator discretion and where allowed by state law. Medical Marijuana must not interfere with the subject's function.

Trial locations and contacts

1 site in 1 country.

Judy Button contact

518-785-1000

jbutton@tristateneuro.com

Vineetha Kamath contact

518-785-1000

vkamath@tristateneuro.com

United States1 site, 1 recruiting

  • Multiple Sclerosis Center of Northeastern New York, P.C.

    Latham, New York, 12110

    Carol L Frazier, 518-785-1000, cfrazier@tristateneuro.com

    Vineetha Kamath, 518-785-1000, vkamath@tristateneuro.com

    Recruiting

Other trials in United States

About this study

Official title: A Prospective Biomarker Study in Active Secondary Progressive Multiple Sclerosis (SPMS)Subjects Treated With Cladribine Tablets

The purpose of this study is to explore the concept that biomarker sensitivity will detect activity in Multiple Sclerosis (MS) subjects and allow appropriate change in treatment to prevent dysfunction.

Read the detailed description

After being informed about the study and potential risks, all patients giving written informed consent will undergo a screening period. Maximum allowable time between first screening procedure and first administration of study treatment will be 42 days.

Subjects will have a 28 day run-in period consisting of 2 visits at week -4 and week -2.

Subjects will have a Baseline day 1 visit. Study medication will commerce on the day following this visit.

Additional visits will be at the following time points: week 4, week 8, week 12, week 16, week 24, week 36, week 48, week 52, week 56, week 60, week 72, week 84 and week 96.

Being tested
Cladribine Tablets
Medical subject headings
Multiple Sclerosis

What participants receive

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

  • Cladribine TabletsDrug

    Also called Mavenclad

    Cladribine tablets will be administered according the current package insert guidelines

Study groups in NCT04550455
Study groupRoleWhat they receive
Cladribine TabletsExperimentalAll participants will receive cladribine tablets according to the current United States Federal Food and Drug Administration (FDA) package guidelines.
Receives: Drug: Cladribine Tablets

What is being measured

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

  1. Time to achieve no evidence of disease activity (NEDA) -4 compared to baseline

    Currently accepted NEDA -3 criteria of 1) no clinical relapses 2) No new or newly enlarging MRI lesions 3) No progression of disability as measured by the expanded disability status scale (EDSS) with 4) the addition of no increase of serum and/or cerebrospinal fluid (CSF) and/or neurofilament light chain (NfL).

    Measured: 96 weeks

  2. Decrease of serum/CSF NfL

    Estimate of the change in serum/CSF NfL values from pre-treatment level to week 48

    Measured: 48 weeks

Secondary outcomes (2)

  1. Change in upper body function

    Change in score, as recorded in seconds, measured by the 9- hole peg test. Lower Score is better

    Measured: 96 weeks

  2. Change in Cognitive Function

    Change in score as measured by the symbol digit modalities test (SDMT). Minimum Score =0 Maximum score =110. Higher Score is better

    Measured: 96 weeks

Timeline

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

  1. First posted16 Sep 2020
  2. Study start16 Sep 2020
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2025 (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
Sequential
Model description
Boxes for treatment cycles distributed will be based on weight
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04550455
Sponsor's protocol ID
Cladribine-001
Status last verified
Jan 2022
First submitted
2 Sep 2020
Last updated
13 Jan 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017 Jun 5;4(4):e360. doi: 10.1212/NXI.0000000000000360. eCollection 2017 Jul.

    PubMed 28626781

  • Bjornevik K, Munger KL, Cortese M, Barro C, Healy BC, Niebuhr DW, Scher AI, Kuhle J, Ascherio A. Serum Neurofilament Light Chain Levels in Patients With Presymptomatic Multiple Sclerosis. JAMA Neurol. 2020 Jan 1;77(1):58-64. doi: 10.1001/jamaneurol.2019.3238.

    PubMed 31515562

  • Brureau A, Blanchard-Bregeon V, Pech C, Hamon S, Chaillou P, Guillemot JC, Barneoud P, Bertrand P, Pradier L, Rooney T, Schussler N. NF-L in cerebrospinal fluid and serum is a biomarker of neuronal damage in an inducible mouse model of neurodegeneration. Neurobiol Dis. 2017 Aug;104:73-84. doi: 10.1016/j.nbd.2017.04.007. Epub 2017 Apr 6.

    PubMed 28392472

  • Comi G, Cook SD, Giovannoni G, Rammohan K, Rieckmann P, Sorensen PS, Vermersch P, Hamlett AC, Viglietta V, Greenberg SJ. MRI outcomes with cladribine tablets for multiple sclerosis in the CLARITY study. J Neurol. 2013 Apr;260(4):1136-46. doi: 10.1007/s00415-012-6775-0. Epub 2012 Dec 21.

    PubMed 23263473

  • Comi G, Cook S, Rammohan K, Soelberg Sorensen P, Vermersch P, Adeniji AK, Dangond F, Giovannoni G. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study. Ther Adv Neurol Disord. 2018 Jan 23;11:1756285617753365. doi: 10.1177/1756285617753365. eCollection 2018.

    PubMed 29399054

  • Edwards KR, Garten L, Button J, O'Connor J, Kamath V, Frazier C. Neurofilament light chain as an indicator of exacerbation prior to clinical symptoms in multiple sclerosis. Mult Scler Relat Disord. 2019 Jun;31:59-61. doi: 10.1016/j.msard.2019.03.016. Epub 2019 Mar 23.

    PubMed 30927733

  • Freedman MS, Leist TP, Comi G, Cree BA, Coyle PK, Hartung HP, Vermersch P, Damian D, Dangond F. The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study. Mult Scler J Exp Transl Clin. 2017 Oct 9;3(4):2055217317732802. doi: 10.1177/2055217317732802. eCollection 2017 Oct-Dec.

    PubMed 29051829

  • Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, Hudson LD, Rudick R; Multiple Sclerosis Outcome Assessments Consortium. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Mult Scler. 2017 Apr;23(5):711-720. doi: 10.1177/1352458517690824. Epub 2017 Feb 16.

    PubMed 28206826

  • Gafson AR, Kim K, Cencioni MT, van Hecke W, Nicholas R, Baranzini SE, Matthews PM. Mononuclear cell transcriptome changes associated with dimethyl fumarate in MS. Neurol Neuroimmunol Neuroinflamm. 2018 Jun 12;5(4):e470. doi: 10.1212/NXI.0000000000000470. eCollection 2018 Jul.

    PubMed 30283812

  • Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sorensen P, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ; CLARITY Study Group. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):416-26. doi: 10.1056/NEJMoa0902533. Epub 2010 Jan 20.

    PubMed 20089960

  • Giovannoni G, Cook S, Rammohan K, Rieckmann P, Sorensen PS, Vermersch P, Hamlett A, Viglietta V, Greenberg S; CLARITY study group. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis. Lancet Neurol. 2011 Apr;10(4):329-37. doi: 10.1016/S1474-4422(11)70023-0.

    PubMed 21397565

  • Giovannoni G, Cutter G, Sormani MP, Belachew S, Hyde R, Koendgen H, Knappertz V, Tomic D, Leppert D, Herndon R, Wheeler-Kingshott CAM, Ciccarelli O, Selwood D, di Cantogno EV, Ben-Amor AF, Matthews P, Carassiti D, Baker D, Schmierer K. Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses. Mult Scler Relat Disord. 2017 Feb;12:70-78. doi: 10.1016/j.msard.2017.01.007. Epub 2017 Jan 17.

    PubMed 28283111

  • Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan KW, Rieckmann P, Comi G, Dangond F, Hicking C, Vermersch P. Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study. Mult Scler. 2019 May;25(6):819-827. doi: 10.1177/1352458518771875. Epub 2018 May 2.

    PubMed 29716436

  • Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G, Dangond F, Adeniji AK, Vermersch P. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler. 2018 Oct;24(12):1594-1604. doi: 10.1177/1352458517727603. Epub 2017 Sep 5.

    PubMed 28870107

  • Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J, Elkins J, O'Neill G; SELECT study investigators. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Jun 22;381(9884):2167-75. doi: 10.1016/S0140-6736(12)62190-4. Epub 2013 Apr 4.

    PubMed 23562009

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cladribine Tablets in people with Multiple Sclerosis, run by Keith Edwards, M.D. at 1 site 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 14 inclusion and 39 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: status not confirmed, as of the sponsor's last update on 13 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Results are not available in the source record.

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

Contact Judy Button (518-785-1000, jbutton@tristateneuro.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to achieve no evidence of disease activity (NEDA) -4 compared to baseline (time frame: 96 weeks). The study lists 2 primary outcomes in all. 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 NCT04550455, which also lists 52 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 13 Jan 2022; AzTrials last refreshed its copy on 30 Oct 2026.

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