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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00641537




Registration number
NCT00641537
Ethics application status
Date submitted
13/03/2008
Date registered
24/03/2008
Date last updated
7/12/2020

Titles & IDs
Public title
CLARITY Extension Study
Scientific title
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)
Secondary ID [1] 0 0
2007-000381-20
Secondary ID [2] 0 0
27820
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing-Remitting Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cladribine
Treatment: Drugs - Placebo
Treatment: Drugs - Cladribine
Treatment: Drugs - Cladribine
Treatment: Drugs - Placebo

Placebo comparator: Cladribine Low/Placebo (LLPP) -

Placebo comparator: Cladribine High Dose/Placebo (HLPP) -

Experimental: Cladribine Low/Low Dose (LLLL) -

Experimental: Cladribine High/Low Dose (HLLL) -

Experimental: Placebo/Cladribine Low Dose (PPLL) -

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).


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline up to Week 120
Primary outcome [2] 0 0
Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120
Timepoint [2] 0 0
Baseline, Week 120
Primary outcome [3] 0 0
Safety Population: Mean Change From Baseline in Hemoglobin at Week 120
Timepoint [3] 0 0
Baseline, Week 120
Primary outcome [4] 0 0
Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120
Timepoint [4] 0 0
Baseline, Week 120
Primary outcome [5] 0 0
Safety Population: Mean Change From Baseline in Bilirubin at Week 120
Timepoint [5] 0 0
Baseline, Week 120
Primary outcome [6] 0 0
Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [6] 0 0
Baseline up to Week 120
Primary outcome [7] 0 0
SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [7] 0 0
Baseline up to Week 120
Primary outcome [8] 0 0
Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Timepoint [8] 0 0
Baseline up to Week 120
Primary outcome [9] 0 0
SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Timepoint [9] 0 0
Baseline up to Week 120
Primary outcome [10] 0 0
Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity
Timepoint [10] 0 0
Baseline up to Week 120
Primary outcome [11] 0 0
Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity
Timepoint [11] 0 0
Baseline up to Week 120
Primary outcome [12] 0 0
Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity
Timepoint [12] 0 0
Baseline up to Week 120
Primary outcome [13] 0 0
Safety Population: Median Time to Nadir of Absolute Lymphocyte Count
Timepoint [13] 0 0
Baseline up to Week 120
Primary outcome [14] 0 0
Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count
Timepoint [14] 0 0
Baseline up to Week 120
Primary outcome [15] 0 0
Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value
Timepoint [15] 0 0
Baseline up to Week 120
Primary outcome [16] 0 0
Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline
Timepoint [16] 0 0
Baseline, Week 5, 48, 52 and 96

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Victoria
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
United States of America
State/province [13] 0 0
West Virginia
Country [14] 0 0
Austria
State/province [14] 0 0
Linz
Country [15] 0 0
Belgium
State/province [15] 0 0
Diepenbeek
Country [16] 0 0
Belgium
State/province [16] 0 0
Esneux
Country [17] 0 0
Brazil
State/province [17] 0 0
Recife
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Pleven
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Plovdiv
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Ruse
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Shuman
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Sofia
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Varna
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Zagora
Country [25] 0 0
Canada
State/province [25] 0 0
Burnaby
Country [26] 0 0
Canada
State/province [26] 0 0
Greenfield Park
Country [27] 0 0
Canada
State/province [27] 0 0
Ottawa
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Croatia
State/province [29] 0 0
Karlovac
Country [30] 0 0
Croatia
State/province [30] 0 0
Sisak
Country [31] 0 0
Croatia
State/province [31] 0 0
Split
Country [32] 0 0
Czechia
State/province [32] 0 0
Hradec Králové
Country [33] 0 0
Czechia
State/province [33] 0 0
Olomouc
Country [34] 0 0
Czechia
State/province [34] 0 0
Praha
Country [35] 0 0
Denmark
State/province [35] 0 0
Copenhagen
Country [36] 0 0
Estonia
State/province [36] 0 0
Tallinn
Country [37] 0 0
Estonia
State/province [37] 0 0
Tartu
Country [38] 0 0
Finland
State/province [38] 0 0
Oulu
Country [39] 0 0
Finland
State/province [39] 0 0
Turku
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France
State/province [40] 0 0
Clermont-Ferrand
Country [41] 0 0
France
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Lille
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France
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Nancy
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France
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Nimes
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France
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Paris
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France
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Rennes
Country [46] 0 0
France
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Saint Herblain
Country [47] 0 0
Germany
State/province [47] 0 0
Bochum
Country [48] 0 0
Germany
State/province [48] 0 0
Frankfurt
Country [49] 0 0
Germany
State/province [49] 0 0
Giessen
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Germany
State/province [50] 0 0
Hannover
Country [51] 0 0
Germany
State/province [51] 0 0
Regensburg
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Germany
State/province [52] 0 0
Rostock
Country [53] 0 0
Greece
State/province [53] 0 0
Athens
Country [54] 0 0
Italy
State/province [54] 0 0
Bari
Country [55] 0 0
Italy
State/province [55] 0 0
Cagliari
Country [56] 0 0
Italy
State/province [56] 0 0
Catania
Country [57] 0 0
Italy
State/province [57] 0 0
Firenze
Country [58] 0 0
Italy
State/province [58] 0 0
Genova
Country [59] 0 0
Italy
State/province [59] 0 0
Milano
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Italy
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Napoli
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Italy
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Padova
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Italy
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Roma
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Latvia
State/province [63] 0 0
Riga
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Lebanon
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Beirut
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Lebanon
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Beyrouth
Country [66] 0 0
Lithuania
State/province [66] 0 0
Kaunas
Country [67] 0 0
Morocco
State/province [67] 0 0
Casablanca
Country [68] 0 0
Morocco
State/province [68] 0 0
Fes
Country [69] 0 0
Morocco
State/province [69] 0 0
Rabat
Country [70] 0 0
Netherlands
State/province [70] 0 0
Sittard- Geleen
Country [71] 0 0
Poland
State/province [71] 0 0
Gdansk
Country [72] 0 0
Poland
State/province [72] 0 0
Krakow
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Poland
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Lodz
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Poland
State/province [74] 0 0
Poznan
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Poland
State/province [75] 0 0
Warszawy
Country [76] 0 0
Portugal
State/province [76] 0 0
Lisboa
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Ekaterinburg
Country [78] 0 0
Russian Federation
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Kaluga
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Kazan
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Russian Federation
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Kemerovo
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Kursk
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Moscow
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Nizhny Novgorod
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Novosibirsk
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Rostov-on-Don
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Samara
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Saratov
Country [88] 0 0
Russian Federation
State/province [88] 0 0
St-Petersburg
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Tomsk
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Vladimir
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Yaroslavl
Country [92] 0 0
Saudi Arabia
State/province [92] 0 0
Riyadh
Country [93] 0 0
Serbia
State/province [93] 0 0
Belgrade
Country [94] 0 0
Switzerland
State/province [94] 0 0
Lausanne
Country [95] 0 0
Switzerland
State/province [95] 0 0
St. Gallen
Country [96] 0 0
Tunisia
State/province [96] 0 0
Monastir
Country [97] 0 0
Tunisia
State/province [97] 0 0
Sfax
Country [98] 0 0
Tunisia
State/province [98] 0 0
Tunis
Country [99] 0 0
Turkey
State/province [99] 0 0
Bursa
Country [100] 0 0
Turkey
State/province [100] 0 0
Izmir
Country [101] 0 0
Ukraine
State/province [101] 0 0
Kharkov
Country [102] 0 0
Ukraine
State/province [102] 0 0
Kiev
Country [103] 0 0
Ukraine
State/province [103] 0 0
Lviv
Country [104] 0 0
Ukraine
State/province [104] 0 0
Vinnitsa
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Hull
Country [106] 0 0
United Kingdom
State/province [106] 0 0
London
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Nottingham
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Oxford
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Sheffield
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Stoke-on-Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.