A Prospective Biomarker Study in Active SPMS Subjects Treated With Cladribine Tablets
NCT ID: NCT04550455
Last Updated: 2022-01-13
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE4
Total Enrollment
30 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-09-16
Study Completion Date
2025-12-31
Brief Summary
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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.
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Detailed Description
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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.
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.
Conditions
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Multiple Sclerosis
Study Design
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Allocation Method
NA
Intervention Model
SEQUENTIAL
Boxes for treatment cycles distributed will be based on weight
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Cladribine Tablets
All participants will receive cladribine tablets according to the current United States Federal Food and Drug Administration (FDA) package guidelines.
Group Type
EXPERIMENTAL
Cladribine Tablets
Intervention Type
DRUG
Cladribine tablets will be administered according the current package insert guidelines
Interventions
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Cladribine Tablets
Cladribine tablets will be administered according the current package insert guidelines
Intervention Type
DRUG
Other Intervention Names
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Mavenclad
Eligibility Criteria
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Inclusion Criteria
1. Male or female between 21 and 65 years old, inclusive.
2. 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.
3. Has an EDSS score at the screening visit of 2.0 to 7.0 inclusive.
4. Have a diagnosis of clinically definite SPMS. (Lublin, 2014)
5. Are considered neurologically stable for \> 30 days prior to both screening, baseline and week 48.
6. Must be otherwise healthy without confounding diseases.
7. Subject has decided to pursue cladribine tablets as their disease modifying therapy (DMT) of choice, and have signed a study specific informed consent form.
8. Must be willing and physically able to comply with all required protocol visits and complete all assessments.
9. Must be willing to complete 2 years of routine clinic follow-ups after study completion as per cladribine tablets FDA guidelines.
10. 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.
11. 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.
12. 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.
13. If Male: must be willing to use contraception to avoid contributing to pregnancies 6 months following the last dose of study medication.
2. 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.
3. Has an EDSS score at the screening visit of 2.0 to 7.0 inclusive.
4. Have a diagnosis of clinically definite SPMS. (Lublin, 2014)
5. Are considered neurologically stable for \> 30 days prior to both screening, baseline and week 48.
6. Must be otherwise healthy without confounding diseases.
7. Subject has decided to pursue cladribine tablets as their disease modifying therapy (DMT) of choice, and have signed a study specific informed consent form.
8. Must be willing and physically able to comply with all required protocol visits and complete all assessments.
9. Must be willing to complete 2 years of routine clinic follow-ups after study completion as per cladribine tablets FDA guidelines.
10. 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.
11. 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.
12. 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.
13. If Male: must be willing to use contraception to avoid contributing to pregnancies 6 months following the last dose of study medication.
Exclusion Criteria
1. Subjects with a diagnosis of a sub-type of MS other than PMS active (clinically definite SPMS)
2. Have MRI findings other than MS that are considered significant per the P.I.
3. Have a clinical condition or medical history noted as a contraindication as per the FDA/US package insert guidelines.
4. Have a history of chronic disease(s) of the immune system, other than MS or a known immunodeficiency syndrome.
5. 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.
6. 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.
7. 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.
8. 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.
a. All standard cancer screening guidelines should be followed for subjects that are treated with cladribine tablets during the course of the study.
9. Known liver conditions including the following:
1. History or current hepatic impairment considered moderate or severe. Subjects with mild hepatic impairment can be considered at the investigator's discretion.
2. Current or known history of alcohol abuse
3. Chronic liver or biliary diseases
4. Total or conjugated bilirubin greater than the upper limit of normal range
5. Alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal range
6. Aspartate transaminase (AST/ aka SGOT) and/or an alanine transaminase (ALT/aka SGPT) greater than 2 times the upper limit of normal range.
7. Gamma-glutamyl-transferase (GGT) greater than 3 times the upper limit of normal.
10. History of or current renal Impairment that is considered moderate to severe. (creatinine clearance below 50 mL per minute)
11. 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).
12. 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.)
13. 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.
14. 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.
15. Unable to undergo the required MRI scans for any reason, including claustrophobia and a history of hypersensitivity to Gd+.
16. 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.
17. Males whose partner plans to become pregnant during the study or become pregnant within 6 months of the last dose of cladribine tablets.
18. Screening labs may be repeated in 2-6 weeks if an abnormality is felt to be due to a transient, reversible condition
19. Subjects that have previously been treated with cladribine in any dosing form (intravenous, subcutaneous, oral) are not allowed.
20. Subjects with a history of any of the following:
1. Prior alemtuzumab treatment
2. Prior or current investigational or non-FDA approved DMT or procedure
3. Prior or current stem cell transplant for any reason
4. Treatment with ocrelizumab or rituximab within 12 months of last dose to baseline
5. 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.
6. Treatment with fingolimod, teriflunomide or dimethyl fumarate (DMF) within 4 weeks prior to baseline
7. Treatment with interferon(IFN) or glatiramer acetate(GA) within 4 weeks of baseline
8. Treatment with Intravenous immune globulin (IVIG) or plasmapheresis within 12 weeks prior to screening
9. Treatment with an immunosuppressant such as cyclophosphamide, mitoxantrone, azathioprine, mycophenolate within 3 years prior to screening.
10. 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
21. 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.
2. Have MRI findings other than MS that are considered significant per the P.I.
3. Have a clinical condition or medical history noted as a contraindication as per the FDA/US package insert guidelines.
4. Have a history of chronic disease(s) of the immune system, other than MS or a known immunodeficiency syndrome.
5. 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.
6. 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.
7. 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.
8. 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.
a. All standard cancer screening guidelines should be followed for subjects that are treated with cladribine tablets during the course of the study.
9. Known liver conditions including the following:
1. History or current hepatic impairment considered moderate or severe. Subjects with mild hepatic impairment can be considered at the investigator's discretion.
2. Current or known history of alcohol abuse
3. Chronic liver or biliary diseases
4. Total or conjugated bilirubin greater than the upper limit of normal range
5. Alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal range
6. Aspartate transaminase (AST/ aka SGOT) and/or an alanine transaminase (ALT/aka SGPT) greater than 2 times the upper limit of normal range.
7. Gamma-glutamyl-transferase (GGT) greater than 3 times the upper limit of normal.
10. History of or current renal Impairment that is considered moderate to severe. (creatinine clearance below 50 mL per minute)
11. 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).
12. 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.)
13. 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.
14. 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.
15. Unable to undergo the required MRI scans for any reason, including claustrophobia and a history of hypersensitivity to Gd+.
16. 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.
17. Males whose partner plans to become pregnant during the study or become pregnant within 6 months of the last dose of cladribine tablets.
18. Screening labs may be repeated in 2-6 weeks if an abnormality is felt to be due to a transient, reversible condition
19. Subjects that have previously been treated with cladribine in any dosing form (intravenous, subcutaneous, oral) are not allowed.
20. Subjects with a history of any of the following:
1. Prior alemtuzumab treatment
2. Prior or current investigational or non-FDA approved DMT or procedure
3. Prior or current stem cell transplant for any reason
4. Treatment with ocrelizumab or rituximab within 12 months of last dose to baseline
5. 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.
6. Treatment with fingolimod, teriflunomide or dimethyl fumarate (DMF) within 4 weeks prior to baseline
7. Treatment with interferon(IFN) or glatiramer acetate(GA) within 4 weeks of baseline
8. Treatment with Intravenous immune globulin (IVIG) or plasmapheresis within 12 weeks prior to screening
9. Treatment with an immunosuppressant such as cyclophosphamide, mitoxantrone, azathioprine, mycophenolate within 3 years prior to screening.
10. 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
21. 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.
Minimum Eligible Age
21 Years
Maximum Eligible Age
65 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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EMD Serono
INDUSTRY
Sponsor Role
collaborator
Keith Edwards, M.D.
OTHER
Sponsor Role
lead
Responsible Party
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Keith Edwards, M.D.
Director
Responsibility Role
SPONSOR_INVESTIGATOR
Principal Investigators
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Keith R Edwards, M.D.
Role: STUDY_DIRECTOR
MS Center of Northeastern New York, P.C.
Locations
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Multiple Sclerosis Center of Northeastern New York, P.C.
Latham, New York, United States
Site Status
RECRUITING
Countries
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United States
Central Contacts
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Facility Contacts
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References
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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.
Reference Type
BACKGROUND
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.
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BACKGROUND
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.
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BACKGROUND
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.
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BACKGROUND
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.
Reference Type
BACKGROUND
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.
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BACKGROUND
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.
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BACKGROUND
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.
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BACKGROUND
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.
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BACKGROUND
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.
Reference Type
BACKGROUND
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.
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BACKGROUND
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.
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BACKGROUND
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.
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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.
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BACKGROUND
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Gregson A, Thompson K, Tsirka SE, Selwood DL. Emerging small-molecule treatments for multiple sclerosis: focus on B cells. F1000Res. 2019 Mar 1;8:F1000 Faculty Rev-245. doi: 10.12688/f1000research.16495.1. eCollection 2019.
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Gunnarsson M, Malmestrom C, Axelsson M, Sundstrom P, Dahle C, Vrethem M, Olsson T, Piehl F, Norgren N, Rosengren L, Svenningsson A, Lycke J. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol. 2011 Jan;69(1):83-9. doi: 10.1002/ana.22247. Epub 2010 Dec 8.
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Havrdova E, Galetta S, Hutchinson M, Stefoski D, Bates D, Polman CH, O'Connor PW, Giovannoni G, Phillips JT, Lublin FD, Pace A, Kim R, Hyde R. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. 2009 Mar;8(3):254-60. doi: 10.1016/S1474-4422(09)70021-3. Epub 2009 Feb 7.
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Havrdova E, Arnold DL, Bar-Or A, Comi G, Hartung HP, Kappos L, Lublin F, Selmaj K, Traboulsee A, Belachew S, Bennett I, Buffels R, Garren H, Han J, Julian L, Napieralski J, Hauser SL, Giovannoni G. No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a. Mult Scler J Exp Transl Clin. 2018 Mar 12;4(1):2055217318760642. doi: 10.1177/2055217318760642. eCollection 2018 Jan-Mar.
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Hermann R, Karlsson MO, Novakovic AM, Terranova N, Fluck M, Munafo A. The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis. Clin Pharmacokinet. 2019 Mar;58(3):283-297. doi: 10.1007/s40262-018-0695-9.
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Hogel H, Rissanen E, Barro C, Matilainen M, Nylund M, Kuhle J, Airas L. Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity. Mult Scler. 2020 Feb;26(2):210-219. doi: 10.1177/1352458518819380. Epub 2018 Dec 20.
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BACKGROUND
Hutchinson M. The only certain measure of the effectiveness of multiple sclerosis therapy is cerebrospinal neurofilament level: Commentary. Mult Scler. 2015 Sep;21(10):1242-3. doi: 10.1177/1352458515599682. Epub 2015 Aug 4. No abstract available.
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BACKGROUND
Kingwell E, Marriott JJ, Jette N, Pringsheim T, Makhani N, Morrow SA, Fisk JD, Evans C, Beland SG, Kulaga S, Dykeman J, Wolfson C, Koch MW, Marrie RA. Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol. 2013 Sep 26;13:128. doi: 10.1186/1471-2377-13-128.
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BACKGROUND
Kuhle J, Plavina T, Barro C, Disanto G, Sangurdekar D, Singh CM, de Moor C, Engle B, Kieseier BC, Fisher E, Kappos L, Rudick RA, Goyal J. Neurofilament light levels are associated with long-term outcomes in multiple sclerosis. Mult Scler. 2020 Nov;26(13):1691-1699. doi: 10.1177/1352458519885613. Epub 2019 Nov 4.
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BACKGROUND
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.
Reference Type
BACKGROUND
Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP, Vermersch P, Casset-Semanaz F, Scaramozza M; oral cladribine for early MS (ORACLE MS) Study Group. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014 Mar;13(3):257-67. doi: 10.1016/S1474-4422(14)70005-5. Epub 2014 Feb 4.
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BACKGROUND
Leppert D, Kuhle J. Serum NfL levels should be used to monitor multiple sclerosis evolution - Yes. Mult Scler. 2020 Jan;26(1):17-19. doi: 10.1177/1352458519872921. Epub 2019 Oct 18. No abstract available.
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Related Links
Access external resources that provide additional context or updates about the study.
https://apps.who.int/iris/handle/10665/43968
Protocol Reference # 9
https://www.emdserono.com/us-en/pi/mavenclad-mg.pdf
Protocol Reference #12
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf
Protocol Reference # 14
https://onlinelibrary.ectrims-congress.eu/ectrims/2017/ACTRIMS-ECTRIMS2017/199999/mitchell.t.wallin.the.prevalence.of.multiple.sclerosis.in.the.united.states.a.html
Protocol Reference #55
https://files.eric.ed.gov/fulltext/ED444296.pdf
Protocol Reference # 61
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Cladribine-001
Identifier Type: -
Identifier Source: org_study_id
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