Trial record 1 of 1 for:    laq-ms-305
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The Efficacy and Safety and Tolerability of Laquinimod in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) (CONCERTO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Teva Pharmaceutical Industries
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT01707992
First received: September 28, 2012
Last updated: September 30, 2014
Last verified: September 2014
  Purpose

This is a multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study followed by active treatment, to evaluate the efficacy, safety and tolerability of two doses of oral administration of laquinimod 0.6 mg/day or 1.2mg/day in subjects with RRMS.


Condition Intervention Phase
Multiple Sclerosis (MS)
Drug: Laquinimod 0.6 mg
Drug: Matching Placebo
Drug: Laquinimod 1.2 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multinational, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-Controlled Study Followed by an Active Treatment Period, to Evaluate the Efficacy, Safety and Tolerability of Two Oral Doses of Laquinimod (0.6 mg/d or 1.2 mg/d) in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS)

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Time to Confirmed Disease Progression (CDP) in Period 1 [ Time Frame: 24 months (Period 1) ] [ Designated as safety issue: No ]
    CDP is defined as an increase in Kurtzke's Expanded Disability Status Scale (EDSS) of 1 point or more from baseline for subjects with baseline EDSS of ≤5.0, or an increase 0.5 points or more from baseline for subjects with baseline EDSS of 5.5. The EDSS rates a person's disability due to multiple sclerosis severity, ranging from 0 (normal neurological exam) to 10 (death due to MS). The higher score represents more severe disability. The outcome measure is the time recorded from Baseline until the subject meets this definition of CDP.


Secondary Outcome Measures:
  • Percent change in brain volume [ Time Frame: Change from Baseline to 15 Months ] [ Designated as safety issue: No ]
    This is a measure of brain volume and will be assessed by an MRI. Brain atrophy is defined as the percent change in brain volume from baseline to month 15


Other Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: 24 months (Period 1) ] [ Designated as safety issue: Yes ]
  • Number of Participants with Abnormal Vital Signs [ Time Frame: 24 months (Period 1) ] [ Designated as safety issue: Yes ]
  • Number of Participants with Abnormal ECG Findings [ Time Frame: 24 months (Period 1) ] [ Designated as safety issue: Yes ]
  • Number of Participants with Abnormal Clinical Laboratory Parameters [ Time Frame: 24 months (Period 1) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 2100
Study Start Date: February 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Laquinimod 0.6 mg
Two capsules, one containing 0.6 mg laquinimod and the other containing matching placebo, to be administered orally once daily during both Periods 1 and 2.
Drug: Laquinimod 0.6 mg
Experimental: Laquinimod 1.2 mg
Two capsules containing 0.6 mg laquinimod to be administered orally once daily during both Periods 1 and 2.
Drug: Laquinimod 1.2 mg
Placebo Comparator: Placebo
Two capsules containing placebo (matching to the 0.6 mg) to be administered orally once daily during Period 1.
Drug: Matching Placebo

Detailed Description:

Eligible subjects with confirmed relapsing-remitting multiple sclerosis will be randomized in a 1:1:1 ratio into one of the following treatment arms: Laquinimod capsules 0.6 mg, Laquinimod capsules 1.2 mg and matching placebo. The study will be comprised of two treatment periods:

Period 1: Double-blind Placebo-controlled (DBPC) period: at least 15 months, but not more than 24 months of once-daily, oral administration of either laquinimod 0.6 mg, 1.2 mg or matching oral placebo.

The Sponsor will declare closing of Period 1 for all subjects when all ongoing enrolled subjects completed at least 15 months in Period 1.

Period 2: Active-treatment (AT) period: 24 months In this period, subjects who were assigned to either 0.6 mg or 1.2 mg daily oral laquinimod during Period 1 (DBPC) will continue with the same treatment assignment, whereas those who were assigned to placebo will receive 1.2 mg daily oral laquinimod.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course.
  • Subjects must be ambulatory with Kurtzke EDSS score of 0- 5.5 in both screening and randomization visits.
  • Subjects must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)] or adrenocorticotrophic hormone (ACTH), 60 days prior to randomization.
  • Subjects must have experienced at least one documented relapse in the 12 months prior to randomization.
  • Subjects must be between 18 and 55 years of age at screening, inclusive.
  • Subjects must have disease duration of at least 6 months, but not more than 12 years (from the first symptom) prior to randomization.

Women of child-bearing potential (for example women who are not postmenopausal or surgically sterilized) must practice an acceptable method of birth control for 30 days before taking the study drug and two acceptable methods of birth control during the duration of the study and until 30 days after the last dose of study medication. Acceptable methods of birth control include: intrauterine devices, barrier method (condom or diaphragm with spermicide) and hormonal methods of birth control (e.g. oral contraceptive, contraceptive patch, and long-acting injectable contraceptive).

  • Subjects must be able to sign and date a written informed consent prior to entering the study.
  • Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

Exclusion Criteria:

  • Subjects with progressive forms of MS.
  • Subjects with Neuromyelitis Optica (NMO).
  • Use of experimental or investigational drugs and/or participation in drug clinical studies within 6 months prior to randomization.
  • Use of immunosuppressive agents,or cytotoxic agents, including Cyclophosphamide within 6 months prior to randomization.
  • Use of either of the following within 2 years prior to screening visit: natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.
  • Use of teriflunomide (Aubagio®) within 2 years prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to randomization.
  • Previous treatment with glatiramer acetate (Copaxone®) Interferon β (either 1a or 1b), fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®) or intravenous immunoglobulin (IVIG) within 2 months prior to randomization.
  • Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization.
  • Previous use of Mitoxantrone (Novantrone®), Cladribine, or alemtuzumab (Lemtrada®).
  • Previous use of laquinimod.
  • Previous total body irradiation or total lymphoid irradiation.
  • Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
  • Use of moderate/strong inhibitors of CYP3A4 within 2 weeks prior to randomization.
  • Use of inducers of CYP3A4 within 2 weeks prior to randomization.
  • Pregnancy or breastfeeding.
  • Serum levels ≥3x upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at screening
  • Serum direct bilirubin which is ≥2xULN at screening.
  • Subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests MRI or chest X-ray. Such conditions may include:

    • A major cardiovascular event (e.g. myocardial infarction, acute coronary syndrome, de-compensated congestive heart failure, pulmonary embolism, coronary revascularization) that occurred during the past 6 months prior to randomization.
    • Any acute pulmonary disorder
    • A CNS disorder other than MS that may jeopardize the subject's participation in the study, including such disorders that are demonstrated on the baseline MRI.
    • A gastrointestinal disorder that may affect the absorption of study medication.
    • Renal disease.
    • Any form of acute or chronic liver disease.
    • Known human immunodeficiency virus positive status.
    • A history of drug and/or alcohol abuse.
    • Unstable psychiatric disorder.
    • Any malignancies, excluding basal cell carcinoma, in the 5 years prior to randomization.
  • A known history of sensitivity to gadolinium (Gd).
  • GFR ≤ 60 mL/min at the screening visit.
  • Inability to successfully undergo MRI scanning.
  • Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI)within 3 months prior to randomization.
  • Known hypersensitivity that would preclude administration of laquinimod capsule, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.
  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: NCT01707992

Contacts
Contact: Teva US Medical Information 1-800-896-5855

  Show 238 Study Locations
Sponsors and Collaborators
Teva Pharmaceutical Industries
Investigators
Study Director: Teva Medical Expert, MD TEVA
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT01707992     History of Changes
Other Study ID Numbers: LAQ-MS-305
Study First Received: September 28, 2012
Last Updated: September 30, 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

ClinicalTrials.gov processed this record on October 20, 2014