CLARITY Extension Study

A Phase IIIb, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects With Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial 25643 (CLARITY)

The purpose of this extension trial was to further evaluate the safety and tolerability of oral cladribine in subjects who have previously completed treatment within Trial 25643 (CLARITY). This trial also explored clinical benefit of prolonged 192-week versus 96-week treatment.

Study Overview

• Status: Completed
• Conditions: Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Placebo; Drug: Cladribine; Drug: Cladribine; Drug: Cladribine

• Study Type: Interventional
• Enrollment (Actual): 867
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
    • Research Site
  • Melbourne, Australia
    • Research Site
  • Victoria, Australia
    • Research Site
• Austria
  • Linz, Austria
    • Research Site
• Belgium
  • Diepenbeek, Belgium
    • Research Site
  • Esneux, Belgium
    • Research Site
• Brazil
  • Recife, Brazil
    • Research Site
• Bulgaria
  • Pleven, Bulgaria
    • Research Site
  • Plovdiv, Bulgaria
    • Research Site
  • Ruse, Bulgaria
    • Research Site
  • Shuman, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Varna, Bulgaria
    • Research Site
  • Zagora, Bulgaria
    • Research Site
• Canada
  • Burnaby, Canada
    • Research Site
  • Greenfield Park, Canada
    • Research Site
  • Ottawa, Canada
    • Research Site
  • Quebec, Canada
    • Research Site
• Croatia
  • Karlovac, Croatia
    • Research Site
  • Sisak, Croatia
    • Research Site
  • Split, Croatia
    • Research Site
• Czechia
  • Hradec Králové, Czechia
    • Research Site
  • Olomouc, Czechia
    • Research Site
  • Praha, Czechia
    • Research Site
• Denmark
  • Copenhagen, Denmark
    • Research Site
• Estonia
  • Tallinn, Estonia
    • Research Site
  • Tartu, Estonia
    • Research Site
• Finland
  • Oulu, Finland
    • Research Site
  • Turku, Finland
    • Research Site
• France
  • Clermont-Ferrand, France
    • Research Site
  • Lille, France
    • Research Site
  • Nancy, France
    • Research Site
  • Nimes, France
    • Research Site
  • Paris, France
    • Research Site
  • Rennes, France
    • Research Site
  • Saint Herblain, France
    • Research Site
• Germany
  • Bochum, Germany
    • Research Site
  • Frankfurt, Germany
    • Research Site
  • Giessen, Germany
    • Research Site
  • Hannover, Germany
    • Research Site
  • Regensburg, Germany
    • Research Site
  • Rostock, Germany
    • Research Site
• Greece
  • Athens, Greece
    • Research Site
• Italy
  • Bari, Italy
    • Research Site
  • Cagliari, Italy
    • Research Site
  • Catania, Italy
    • Research Site
  • Firenze, Italy
    • Research Site
  • Genova, Italy
    • Research Site
  • Milano, Italy
    • Research Site
  • Napoli, Italy
    • Research Site
  • Padova, Italy
    • Research Site
  • Roma, Italy
    • Research Site
• Latvia
  • Riga, Latvia
    • Research Site
• Lebanon
  • Beirut, Lebanon
    • Research Site
  • Beyrouth, Lebanon
    • Research Site
• Lithuania
  • Kaunas, Lithuania
    • Research Site
• Morocco
  • Casablanca, Morocco
    • Research Site
  • Fes, Morocco
    • Research Site
  • Rabat, Morocco
    • Research Site
• Netherlands
  • Sittard- Geleen, Netherlands
    • Research Site
• Poland
  • Gdansk, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Lodz, Poland
    • Research Site
  • Poznan, Poland
    • Research Site
  • Warszawy, Poland
    • Research Site
• Portugal
  • Lisboa, Portugal
    • Research Site
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Research Site
  • Kaluga, Russian Federation
    • Research Site
  • Kazan, Russian Federation
    • Research Site
  • Kemerovo, Russian Federation
    • Research Site
  • Kursk, Russian Federation
    • Research Site
  • Moscow, Russian Federation
    • Research Site
  • Nizhny Novgorod, Russian Federation
    • Research Site
  • Novosibirsk, Russian Federation
    • Research Site
  • Rostov-on-Don, Russian Federation
    • Research Site
  • Samara, Russian Federation
    • Research Site
  • Saratov, Russian Federation
    • Reseach Site
  • St-Petersburg, Russian Federation
    • Research Site
  • Tomsk, Russian Federation
    • Research Site
  • Vladimir, Russian Federation
    • Research Site
  • Yaroslavl, Russian Federation
    • Research Site
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Research Site
• Serbia
  • Belgrade, Serbia
    • Research Site
• Switzerland
  • Lausanne, Switzerland
    • Research Site
  • St. Gallen, Switzerland
    • Research Site
• Tunisia
  • Monastir, Tunisia
    • Research Site
  • Sfax, Tunisia
    • Research Site
  • Tunis, Tunisia
    • Research Site
• Turkey
  • Bursa, Turkey
    • Research Site
  • Izmir, Turkey
    • Research Site
• Ukraine
  • Kharkov, Ukraine
    • Research Site
  • Kiev, Ukraine
    • Research Site
  • Lviv, Ukraine
    • Research Site
  • Vinnitsa, Ukraine
    • Research Site
• United Kingdom
  • Hull, United Kingdom
    • Research Site
  • London, United Kingdom
    • Research Site
  • Nottingham, United Kingdom
    • Research Site
  • Oxford, United Kingdom
    • Research Site
  • Sheffield, United Kingdom
    • Research Site
  • Stoke-on-Trent, United Kingdom
    • Research Site
• United States
  • Colorado
    • Boulder, Colorado, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
  • Illinois
    • Chicago, Illinois, United States
      • Research Site
    • Northbrook, Illinois, United States
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States
      • Research Site
  • Nevada
    • Henderson, Nevada, United States
      • Research Site
  • New Jersey
    • Newark, New Jersey, United States
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Research Site
    • Durham, North Carolina, United States
      • Research Site
  • Ohio
    • Columbus, Ohio, United States
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Research Site
    • Tulsa, Oklahoma, United States
      • Research Site
  • Oregon
    • Medford, Oregon, United States
      • Research Site
  • Washington
    • Seattle, Washington, United States
      • Research Site
    • Tacoma, Washington, United States
      • Research Site
  • West Virginia
    • Charleston, West Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Randomized in Trial 25643 and satisfied one of the following:

  • Completed randomized treatment course and scheduled visits for the full 96 weeks; or
  • Did not complete the randomized treatment course in Trial 25643 but elected to receive rescue treatment with Rebif®, another beta-interferon, or glatiramer acetate and completed scheduled clinic visits for the full 96 weeks; or
  • Did not complete the randomized treatment course in Trial 25643, declined rescue with Rebif®, another beta-interferon, or glatiramer acetate and still completed scheduled clinic visits for the full 96 weeks; or
  • Did not complete the randomized treatment course in Trial 25643, were not eligible for rescue option with Rebif®, and still completed scheduled clinic visits for the full 96 weeks
• Male or female, between 18 and 65 years of age (inclusive, at time of informed consent for Trial 25643)
• No medical history or evidence of latent tuberculosis infection (LTBI) or tuberculosis (TB), as evidenced by TB skin test or chest X-ray

• All of the following laboratory hematologic parameters evaluated as normal (as define below, inclusively) within 28 days of first dosing of blinded study medication at study Day 1:

  • Hemoglobin = 11.6 to 16.2 gram per deciliter (g/dL)
  • Leukocytes (total white blood cell) = 4.1 to 12.3*10^3 per microliter
  • Absolute lymphocyte count (ALC) = 1.02 to 3.36*10^3 per microliter
  • Absolute neutrophil count (ANC) = 2.03 to 8.36*10^3 per microliter
  • Platelet count = 140 to 450*10^3 per microliter
• Other protocol-defined inclusion/exclusion criteria may apply

Exclusion Criteria:

• Participants who were not enrolled in Trial 25643
• Participant has moderate to severe renal impairment
• Use of mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab at any time during and since Trial 25643
• Use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIG) or plasmapheresis at any time during and since Trial 25643
• Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days before Study Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Cladribine Low/Placebo (LLPP)	Drug: Placebo; Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.; Drug: Placebo; Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.
Placebo Comparator: Cladribine High Dose/Placebo (HLPP)	Drug: Placebo; Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.; Drug: Placebo; Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.
Experimental: Cladribine Low/Low Dose (LLLL)	Drug: Cladribine; Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Drug: Cladribine; Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Drug: Cladribine; Participants who received placebo in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
Experimental: Cladribine High/Low Dose (HLLL)	Drug: Cladribine; Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Drug: Cladribine; Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Drug: Cladribine; Participants who received placebo in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
Experimental: Placebo/Cladribine Low Dose (PPLL)	Drug: Cladribine; Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Drug: Cladribine; Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Drug: Cladribine; Participants who received placebo in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
No Intervention: Placebo/No Treatment
No Intervention: Cladribine 3.5 mg/kg/No Treatment; Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period).
No Intervention: Cladribine 5.25 mg/kg/No Treatment; Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity	Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.	Baseline up to Week 120
Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120	Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported.	Baseline, Week 120
Safety Population: Mean Change From Baseline in Hemoglobin at Week 120	Mean change from baseline in hemoglobin at Week 120 was reported.	Baseline, Week 120
Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120	Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported.	Baseline, Week 120
Safety Population: Mean Change From Baseline in Bilirubin at Week 120	Mean Change From Baseline in Bilirubin at week 120 was reported.	Baseline, Week 120
Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.	Baseline up to Week 120
SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.	Baseline up to Week 120
Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies	Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.	Baseline up to Week 120
SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies	Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.	Baseline up to Week 120
Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity	Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve.	Baseline up to Week 120
Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity	Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.	Baseline up to Week 120
Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity	Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.	Baseline up to Week 120
Safety Population: Median Time to Nadir of Absolute Lymphocyte Count	Median time to nadir of absolute lymphocyte count was reported.	Baseline up to Week 120
Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count	Mean time to nadir of absolute lymphocyte count was reported.	Baseline up to Week 120
Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value	Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10^3 cells/microliter.	Baseline up to Week 120
Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline	The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported.	Baseline, Week 5, 48, 52 and 96

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2008
• Primary Completion (Actual): December 31, 2011
• Study Completion (Actual): December 31, 2011

Study Registration Dates

• First Submitted: March 13, 2008
• First Submitted That Met QC Criteria: March 21, 2008
• First Posted (Estimate): March 24, 2008

Study Record Updates

• Last Update Posted (Actual): December 7, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cladribine
• Other Study ID Numbers: 27820; 2007-000381-20 (EudraCT Number)