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CLARITY Extension Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00641537
First received: March 13, 2008
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

The purpose of this extension trial is 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.


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Drug: Cladribine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Lymphocyte Toxicity [ Time Frame: Baseline up to Week 120 ] [ Designated as safety issue: Yes ]
    Lymphocyte toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). CTCAE grade for absolute lymphocyte counts included: Grade 1 = less than lower limit of normal; Grade 2 = less than 800 per cubic millimeter (/mm^3); Grade 3 = less than 500/mm^3; Grade 4 = less than 200/mm^3.

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to week 120 ] [ Designated as safety issue: Yes ]
    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.

  • Median Time to Recovery From Grade 3 or 4 Lymphocyte Toxicity [ Time Frame: Baseline up to Week 120 ] [ Designated as safety issue: Yes ]
    Lymphocyte toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). CTCAE grade for absolute lymphocyte counts included: Grade 1 = less than lower limit of normal; Grade 2 = less than 800 per cubic millimeter (/mm^3); Grade 3 = less than 500/mm^3; Grade 4 = less than 200/mm^3. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1 during the CLARITY Extension Study.

  • Number of Participants Who Developed Herpes Zoster Infections and Malignancies [ Time Frame: Baseline up to Week 120 ] [ Designated as safety issue: Yes ]
    Herpes zoster infection is defined as having at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms herpes zoster, herpes zoster iridocyclitis, herpes zoster ophthalmic, herpes zoster multi-dermatomal, herpes zoster infection neurological, herpes zoster oticus. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre_specified grouping Malignant and unspecified tumors.


Secondary Outcome Measures:
  • Annualized Qualifying Relapse Rate [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.

  • Mean Number of Combined Unique (CU) Lesions [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Mean Number of CU lesions were measured by using magnetic resonance imaging (MRI) scans.

  • Time to Disability Progression (Confirmed After 3 Months) [ Time Frame: Baseline up to Week 96 ] [ Designated as safety issue: No ]
    Time to disability progression was defined as the time to a sustained increase in EDSS score of at least 1 point if baseline EDSS score between 0.5 and 4.5 inclusively, or at least 1.5 points if the baseline EDSS score was 0, or at least 0.5 point if the baseline EDSS score was at least 5, over a period of at least three months. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. As few participants have reached EDSS progression, fourth Percentile of time to sustained increase in EDSS score was reported using Kaplan-Meier survival curve.


Enrollment: 867
Study Start Date: February 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Placebo Comparator: Cladribine High Dose/Placebo (HLPP) 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.
Experimental: Cladribine High/Low Dose (HLLL) 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.
Experimental: Placebo/Cladribine Low Dose (PPLL) 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  • Subjects who were not enrolled in Trial 25643
  • Subject 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00641537

  Show 117 Study Locations
Sponsors and Collaborators
EMD Serono
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00641537     History of Changes
Other Study ID Numbers: 27820
Study First Received: March 13, 2008
Results First Received: September 30, 2013
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Cladribine
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014