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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
29/02/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2011
Sample size
Target
Accrual to date
Final
867
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
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Colorado
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Georgia
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Illinois
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Maryland
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Michigan
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Nevada
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New Jersey
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Washington
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West Virginia
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Austria
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Linz
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Diepenbeek
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Esneux
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Recife
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Pleven
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Plovdiv
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Ruse
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Shuman
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Sofia
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Varna
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Zagora
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Hradec Králové
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Bochum
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Frankfurt
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Giessen
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Hannover
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Fes
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Rabat
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Novosibirsk
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Russian Federation
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Rostov-on-Don
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Russian Federation
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Samara
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Russian Federation
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Saratov
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Russian Federation
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St-Petersburg
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Russian Federation
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Tomsk
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Russian Federation
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Vladimir
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Russian Federation
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Yaroslavl
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Saudi Arabia
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Riyadh
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Serbia
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Belgrade
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Switzerland
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Lausanne
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Switzerland
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St. Gallen
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Tunisia
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Monastir
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Tunisia
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Sfax
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Tunisia
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Tunis
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Turkey
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Bursa
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Turkey
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Izmir
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Ukraine
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Kharkov
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Ukraine
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Kiev
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Ukraine
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Lviv
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Ukraine
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Vinnitsa
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United Kingdom
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Hull
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United Kingdom
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London
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United Kingdom
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Nottingham
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United Kingdom
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Oxford
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United Kingdom
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Sheffield
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United Kingdom
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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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00641537
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00641537