The Efficacy, Safety, and Tolerability of Laquinimod in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) (CONCERTO)

Teva Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Multiple Sclerosis

Treatments: Drug: Placebo; Drug: Laquinimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT01707992

2012-003647-30 (EudraCT Number)

LAQ-MS-305

Details and patient eligibility

About

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 in participants with RRMS. The study has 2 periods: Period 1, the double-blind, placebo-controlled period (up to 24 months) and Period 2, the active treatment period (24 months).

Enrollment: 2,199 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course.

• Participants must be ambulatory with Kurtzke's expanded disability status scale (EDSS) score of 0 to 5.5 in both screening and randomization visits.

• Participants must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)/oral] or adrenocorticotrophic hormone, 60 days prior to randomization.

• Participants must have experienced at least one documented relapse in the 12 months prior to randomization.

• Participants must have disease duration of not more than 15 years.

• 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.

  • Additional criteria apply, please contact the investigator for more information.

Exclusion criteria

• Participants with progressive forms of MS.

• Participants with neuromyelitis optica.

• Use of experimental or investigational drugs and/or participation in drug clinical studies within the 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 randomization 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 immunoglobulins 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 cytochrome P450 (CYP) 3A4 within 2 weeks prior to randomization.

• Use of inducers of CYP3A4 within 2 weeks prior to randomization visit.

• Pregnancy or breastfeeding.

• A known history of sensitivity to gadolinium (Gd).

• Inability to successfully undergo magnetic resonance imaging (MRI) scanning.

• Participants who underwent endovascular treatment for chronic cerebrospinal venous insufficiency within 3 months prior to randomization.

  • Additional criteria apply, please contact the investigator for more information.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,199 participants in 6 patient groups, including a placebo group

Placebo-Controlled Phase: Placebo

Placebo Comparator group

Description:

Participants will receive 2 capsules of placebo (matching to laquinimod 0.6 milligrams \[mg\]) once daily orally for up to 24 months.

Treatment:

Drug: Placebo

Placebo-Controlled Phase: Laquinimod 0.6 mg

Experimental group

Description:

Participants will receive 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months.

Treatment:

Drug: Laquinimod

Drug: Placebo

Placebo-Controlled Phase: Laquinimod 1.2 mg

Experimental group

Description:

Participants will receive laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.

Treatment:

Drug: Laquinimod

Active Treatment Phase: Laquinimod 0.6 mg

Experimental group

Description:

Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, will receive 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months.

Treatment:

Drug: Laquinimod

Drug: Placebo

Active Treatment Phase: Laquinimod 1.2 mg

Experimental group

Description:

Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, will receive laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.

Treatment:

Drug: Laquinimod

Active Treatment Phase: Off Drug

No Intervention group

Description:

Participants who were discontinued from treatment with laquinimod 1.2 mg during the placebo-controlled phase due to sponsor decision after 01 January 2016 will continue the active-treatment phase off drug for 24 months.