A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

NCT00213135 | Completed Phase 3 Results

• 1 other identifier: 25643
• Study Type: interventional
• Target: 1,326
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to determine if cladribine tablets are a safe and effective treatment for relapsing-remitting multiple sclerosis (RRMS).

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• Annualized Qualifying Relapse Rate

  A qualifying relapse was defined as an increase of 2 points in at least one functional system of the expanded disability status scale (EDSS) or an increase of 1 point in at least two functional systems (excluding changes in bowel or bladder function or cognition) in the absence of fever, lasting for at least 24 hours and to have been preceded by at least 30 days of clinical stability or improvement. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]) was calculated. The annualized relapse rate for each treatment group was calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.

  Week 96

Secondary Outcomes (3)

• Percentage of Relapse-free Participants

  Week 96

• Time to Disability Progression

  Baseline up to Week 96

• Mean Number of Combined Unique (CU) Lesions, Active Time Constant 2 (T2) Lesions, and Active Time Constant 1 (T1) Gadolinium-Enhanced (Gd+) Lesions Per Participant Per Scan

  Week 96

Study Arms (3)

Cladribine 5.25 mg/kg

EXPERIMENTAL

Drug: Cladribine 5.25 mg/kg

Cladribine 3.5 mg/kg

EXPERIMENTAL

Drug: Cladribine 3.5 mg/kg

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Cladribine 5.25 mg/kg DRUG

Cladribine tablet will be administered as cumulative dose of 0.875 milligram per kilogram (mg/kg) over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the treatment period of 96 weeks.

Cladribine 5.25 mg/kg

Cladribine 3.5 mg/kg DRUG

Cladribine tablet will be administered as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Weeks 1, 5, 48, and 52 and placebo matched to cladribine tablet will be administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Cladribine 3.5 mg/kg

Placebo OTHER

Placebo matched to cladribine tablet will be administered over a course of 4 or 5 consecutive days of 28-day period at Weeks 1, 5, 9, 13, 48 and 52 during the treatment period of 96 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, between 18 and 65 years of age (inclusive, at time of informed consent)
• Has definite MS according to the McDonald criteria
• Has relapsing-remitting disease with 1 or more relapses within 12 months prior to Study Day 1
• Must have been clinically stable and not has a relapse within 28 days prior to Study Day 1
• Has MRI consistent with MS at the pre-study evaluation according to the Fazekas criteria
• Has a EDSS score from 0 to 5.5, inclusive
• Weighed between 40-120 kilogram (kg), inclusive
• If female, she must:
• be post-menopausal or surgically sterilized; or
• uses a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and
• be neither pregnant nor breast-feeding
• If male, he must be willing to use contraception to avoid pregnancies
• Be willing and able to comply with study procedures for the duration of the study
• Voluntarily provides written informed consent, and for United states of America (USA) sites only, a subject authorization under Health Insurance Portability and Accountability Act (HIPAA)

You may not qualify if:

• Has secondary progressive MS (SPMS) or primary progressive MS (PPMS)
• Prior use of disease modifying drugs (DMDs) within the last 3 months, or 2 or more prior treatment failures with DMDs on the basis of efficacy
• Has significant leukopenia (white blood cell count less than 0.5 times the lower limit of normal of the central laboratory) within 28 days prior to Study Day 1
• Has received cladribine, mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab
• Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1
• Has compromised immune function or infection
• Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1
• Has received cytokine-based therapy, intravenous immunoglobulin therapy, or plasmapheresis within 3 months prior to Study Day 1
• Has platelet and absolute neutrophil counts below the lower limit of normal range within 28 days prior to Study Day 1
• Has prior or current history of malignancy
• Has a history of persistent anemia, leukopenia, neutropenia, or thrombocytopenia after immunosuppressive therapy
• Has systemic disease that, in the opinion of the Investigator, might interfere with subject safety, compliance or evaluation of the condition under Study (for example, insulin-dependent diabetes, Lyme disease, clinically significant cardiac, hepatic, or renal disease, Human Immunodeficiency Virus, or Human T-Cell Lymphotrophic Virus Type-1)
• Has a psychiatric disorder that, in the opinion of the Investigator, was unstable or would preclude safe participation in the study
• Has allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients
• Has used any investigational drug or experimental procedure within 6 months prior to Study Day 1

Sponsors & Collaborators

• EMD Serono: lead

Related Publications (14)

• 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.

  PMID: 20089960 RESULT

• Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist TP, Coyle PK, Dangond F, Alexandri N, Galazka A. Relapses in people with multiple sclerosis treated with cladribine tablets followed for up to 5 years: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):303-310. doi: 10.2217/nmt-2022-0019. Epub 2022 Aug 26.

  PMID: 36017797 DERIVED

• Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Jack D, Vermersch P. Disease stability over five years in people with multiple sclerosis treated with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):295-301. doi: 10.2217/nmt-2022-0018. Epub 2022 Aug 26.

  PMID: 36017780 DERIVED

• Vermersch P, Galazka A, Dangond F, Damian D, Wong SL, Jack D, Harty G. The effect of cladribine tablets in people with more active multiple sclerosis: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):285-293. doi: 10.2217/nmt-2022-0009. Epub 2022 Aug 3.

  PMID: 35920065 DERIVED

• Oh J, Walker B, Giovannoni G, Jack D, Dangond F, Nolting A, Aldridge J, Lebson LA, Leist TP. Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Feb 1;12(1):1-7. doi: 10.2217/nmt-2021-0041. Epub 2022 Jan 12.

  PMID: 35019731 DERIVED

• Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.

  PMID: 35003076 DERIVED

• Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Keller B, Jack D, Vermersch P. Long-Term Disease Stability Assessed by the Expanded Disability Status Scale in Patients Treated with Cladribine Tablets 3.5 mg/kg for Relapsing Multiple Sclerosis: An Exploratory Post Hoc Analysis of the CLARITY and CLARITY Extension Studies. Adv Ther. 2021 Sep;38(9):4975-4985. doi: 10.1007/s12325-021-01865-w. Epub 2021 Aug 9.

  PMID: 34370275 DERIVED

• De Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist T, Coyle PK, Dangond F, Keller B, Alexandri N, Galazka A. Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies. Mult Scler. 2022 Jan;28(1):111-120. doi: 10.1177/13524585211010294. Epub 2021 May 10.

  PMID: 33969750 DERIVED

• Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.

  PMID: 32447743 DERIVED

• Terranova N, Hicking C, Dangond F, Munafo A. Effects of Postponing Treatment in the Second Year of Cladribine Administration: Clinical Trial Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis. Clin Pharmacokinet. 2019 Mar;58(3):325-333. doi: 10.1007/s40262-018-0693-y.

  PMID: 29992396 DERIVED

• Afolabi D, Albor C, Zalewski L, Altmann DR, Baker D, Schmierer K. Positive impact of cladribine on quality of life in people with relapsing multiple sclerosis. Mult Scler. 2018 Oct;24(11):1461-1468. doi: 10.1177/1352458517726380. Epub 2017 Aug 17.

  PMID: 28817997 DERIVED

• Savic RM, Novakovic AM, Ekblom M, Munafo A, Karlsson MO. Population Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis. Clin Pharmacokinet. 2017 Oct;56(10):1245-1253. doi: 10.1007/s40262-017-0516-6.

  PMID: 28255849 DERIVED

• De Stefano N, Giorgio A, Battaglini M, De Leucio A, Hicking C, Dangond F, Giovannoni G, Sormani MP. Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets. Mult Scler. 2018 Feb;24(2):222-226. doi: 10.1177/1352458517690269. Epub 2017 Jan 31.

  PMID: 28140753 DERIVED

• Ali S, Paracha N, Cook S, Giovannoni G, Comi G, Rammohan K, Rieckmann P, Sorensen PS, Vermersch P, Greenberg S, Scott DA, Joyeux A; CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) Study Group. Reduction in healthcare and societal resource utilization associated with cladribine tablets in patients with relapsing-remitting multiple sclerosis: analysis of economic data from the CLARITY Study. Clin Drug Investig. 2012 Jan 1;32(1):15-27. doi: 10.2165/11593310-000000000-00000.

  PMID: 22017519 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Steven J. Greenberg, M.D.

  EMD Serono

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: April 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: February 7, 2014
• Results First Posted: December 2, 2013

Record last verified: 2014-01