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).

• Conditions: Relapsing Remitting Multiple Sclerosis (RRMS); MedDRA version: 9.1Level: PTClassification code 10028245Term: Multiple sclerosis

• Registration Number: EUCTR2007-000381-20-PT
• Lead Sponsor: Merck Serono S.A. - Geneva

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01-15
• Last Update Posted: 25 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1100

Inclusion Criteria

° Were randomised in Trial 25643 and satisfy one of the following:
- Completed their randomised treatment course and scheduled visits for the full 96 weeks (a)(b); or
- Did not complete the randomized treatment course in Trial 25643, but who elected to receive rescue treatment with Rebif or another DMD, and who completed scheduled clinic visits for the full 96 weeks (a)(b); or
- Did not complete the randomised treatment course in Trial 25643, declined rescue with Rebif or another DMD, and still completed scheduled clinic visits for the full 96 weeks (a)(b); or
- Did not complete the randomised treatment course in Trial 25643, were not eligible for rescue option with Rebif, and still completed scheduled clinic visits for the full 96 weeks (a)(b).

° Be male or female and between 18 and 65 years of age (inclusive, at time of informed consent prior to entry into Trial 25643)

° Have no medical history or evidence of latent tuberculosis infection (LTBI) or active
tubercular disease (TB), as evidenced by TB skin test or chest X-ray;
NOTE: For subjects with medical history or LTBI ot TB, please refer to Appendices L, M, N. Subjects who should be excluded from blinded medication could be proposed to be followed for safety according to the same scheduled visits

° All of the following laboratory hematologic parameters must be normal (as defined below, inclusively) within 28 days of first dosing of blinded study medication at SD1:
- Hemoglobin = 11.6 – 16.2 G/DL
- Leukocyctes (total white blood cells [WBC]) = 4.1 – 12.3 x 10E3/UL
- Absolute lymphocytes = 1.02 – 3.36 x 10E3/UL
- Absolute neutrophil count (ANC) = 2.03 – 8.36 x10E3/UL
- Platelet count = 140-450 x 10E3/UL
NOTE: For subjects with abnormal laboratory hematological parameters, please refer to section 6.2.1 for retesting guidelines. Subjects who should be excluded from blinded medication during the current yearly dosing could be proposed to be followed for safety according to the same scheduled visits.

° Female subjects must be neither pregnant nor breast-feeding and must lack child-bearing potential, as defined by either:
- Be post-menopausal or surgically sterilized; or
- Using a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication or following early termination or early withdrawal. A highly effective method of contraception is defined as those which result in a low failure rate (i.e. less that 1% per year) when used consistently and correctly such as implants, injectables, comined with oral contraceptives, IUSs, sexual abstinence or vasectomised partner. [Note: for Danish sites only, subjects should use a hormonal contraceptive or intrauterine device for the duration of the trial]

° Treatment of pregnant and nursing women with cladribine is prohibited.

° If male, he must be willing to use contraception to avoid pregnancies throughout the entire duration of the study and for 90 days following the last dose of study medication or following early termination or early withdrawal.

° Subject must be willing and able to participate in the trial and have provided written, informed consent

° Voluntarily provide written informed consent, and for USA sites only, a subject authorization under Health Insurance Portability and Accountability Act (HIPAA)

Females of childbearing potential, who are either subjects in the trial or who are partners to male subjects in the trial, must use one

Exclusion Criteria

° Have prior or current malignancy other than medically documented complete excision of basal cell skin cancer no less than 5 years prior to Screening;

° Have a history of chronic or clinically significant hematological abnormalities;

° Has inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 2.5 times the upper limit of the normal values;

° Suffers from major medical illness such as cardiac, endocrinologic, hepatic, immunologic (other than MS), metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine.

° Suffers from major psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol;

° History of active or chronic infectious disease or any disease which compromises immune function (e.g. HIV+, HTLV-1, Lyme disease);

° Have an allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients, or IFN-b or any of its excipient(s);

° Have any renal condition that would preclude the administration of gadolinium (e.g. acute or chronic severe renal insufficiency (GFR < 30mL/min/1.73m2);

° Have a positive stool heme-occult test at Pre-Study Evaluation (PSE);
NOTE: For subjects with positive heme-occult test, please refer to section 6.2.1 for retesting guidelines. Subjects who should be excluded from blinded medication during the current yearly dosing could be proposed to be followed for safety according to the same scheduled visits.

° Subject has a history of seizures not adequately controlled by treatment.

° Concurrent enrolment in any other investigational drug trial with the exception of any Sponsor sub-trial of this protocol that is approved by the Medical Director

° Any other reason(s) that, in the opinion of the Investigator and/or the Sponsor, would indicate that the subject is unsuitable for inclusion in this extension trial

° Treatment with a DMD less than 3 months prior to Study Day 1 during any gap between completion of CLARITY Trial 25643 and CLARITY Extension Trial 27820

° Use of mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab at anytime during and since Study 25643

NOTE: For subjects who had to delay entry into the CLARITY Extension study whereby there was a gap interval of varying duration, who subsequently, during the gap interval were treated with a DMD or Rebif should discontinue the DMD or Rebif for a period of at least 3 months prior to Study Day 1. For those subjects who are unable or are unwilling to discontinue their DMD, they may not be re- randomized to receive study medication. These subjects are encouraged to enter the study but will be followed for safety only.

NOTE: For subjects who had to delay entry into the CLARITY Extension study, whereby there was a gap interval of varying duration, who subsequently during the gap interval were treated with a prohibited medication (See exclusion criteria section 5.2.2.) are not able to be re-randomized to receive study medication in the CLARITY Extension study. These subjects are encouraged to enter the study, but will be followed for safety only.

° Use of cytokine or anti-cytokine therapy, intravenous immunog

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified