A clinical study in subjects with relapsing-remitting multiple sclerosis (RRMS) consisting of two parts: First part is to assess the efficacy, safety and tolerability of two oral doses of laquinimod either of 0.6 mg/day or 1.2mg/day (experimental drug) as compared placebo. Second part (all subjects receiving active treatment) is to evaluate the efficacy, safety and tolerability of two oral doses of laquinimod 0.6 mg/day or 1.2 mg/day (experimental drug).

• Register: EUCTR
• Last refreshed on: 29 May 2017
• Main ID: EUCTR2012-003647-30-HU
• Date of registration: 25/10/2012
• Prospective Registration: Yes
• Primary sponsor: Teva Pharmaceutical Industries Ltd
• Public title: A clinical study in subjects with relapsing-remitting multiple sclerosis (RRMS) consisting of two parts: First part is to assess the efficacy, safety and tolerability of two oral doses of laquinimod either of 0.6 mg/day or 1.2mg/day (experimental drug) as compared placebo. Second part (all subjects receiving active treatment) is to evaluate the efficacy, safety and tolerability of two oral doses of laquinimod 0.6 mg/day or 1.2 mg/day (experimental drug).
• Scientific 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 doses of oral administration of laquinimod (0.6 mg/day or 1.2 mg/day) in subjects with relapsing remitting multiple sclerosis (RRMS) - CONCERTO
• Date of first enrolment: 04/01/2013
• Target sample size: 2199
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003647-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Chile, Croatia, Czech Republic, Estonia, Georgia, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Latvia, Macedonia, the former Yugoslav Republic of, Moldova, Republic of, Montenegro, Poland, Russian Federation, Serbia, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Teva GmbH

• Name: Clinical Trial Information Desk
• Affiliation: Teva GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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.
2. Subjects must be ambulatory with Kurtzke EDSS score of 0-5.5 in both screening and randomization visits.
3.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.
4. Subjects must have experienced at least one documented relapse in the 12 months prior to randomization.
5. Subjects must be between 18 and 55 years of age at screening, inclusive.
6. Subjects must have disease duration of not more than 15 years.
7. Women of child-bearing potential 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.
8. Subjects must be able to sign and date a written informed consent prior to entering the study.
9. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2199
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects with progressive forms of MS.
2. Subjects with Neuromyelitis Optica (NMO).
3.Use of experimental or investigational drugs and/or participation in drug clinical studies within 6 months prior to randomization.
4.Use of immunosuppressive agents or cytotoxic agents, including Cyclophosphamide within 6 months prior to randomization.
5.Use of either of the following within 2 years prior to randomization: natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.
6.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.
7.Previous treatment with glatiramer acetate (Copaxone®) Interferon ß
(either 1a or 1b), fingolimod (Gilenya®), dimethyl fumarate
(Tecfidera®) or intravenous immunoglobulin (IVIG) within 2 months
prior to randomization.
8.Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization.
9.Previous use of Mitoxantrone (Novantrone®), Cladribine, or
alemtuzumab (Lemtrada®).
10.Previous use of laquinimod.
11.Previous total body irradiation or total lymphoid irradiation.
12.Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
13.Use of moderate/strong inhibitors of CYP3A4 within 2 weeks prior to randomization.
14.Use of inducers of CYP3A4 within 2 weeks prior to randomization.
15.Pregnancy or breastfeeding.
16.Serum levels =3x upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at screening.
17.Serum direct bilirubin which is =2xULN at screening.
18.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.
19.A known history of sensitivity to gadolinium (Gd).
20.GFR = 60 mL/min at the screening visit.
21.Inability to successfully undergo MRI scanning.
22.Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI) within 3 months prior to randomization.
23.Known hypersensitivity that would preclude administration of laquinimod capsule, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing remitting multiple sclerosis
MedDRA version: 19.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Laquinimod capsules 0.6 mg
Product Code: TV-5600
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LAQUINIMOD
CAS Number: 248282-07-7
Current Sponsor code: TV-5600
Other descriptive name: Laquinimod Sodium (USAN)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.6-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Time to Confirmed Disease Progression (CDP) during Period 1.
CDP is defined as an increase in EDSS of =1 point from baseline for subjects with baseline EDSS of =5.0, or an increase in EDSS of = 0.5 points from baseline for subjects with baseline EDSS of 5.5. Analysis will be performed at the completion of Period 1.

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Evaluation will be performed at months -1 (screening), 0 (baseline) and every 3 months thereafter and until completion visit of Period 1

Main Objective: To assess the efficacy, safety and tolerability of a daily dose of 0.6 mg and 1.2 mg of laquinimod as compared to placebo in subjects with relapsing remitting multiple sclerosis (RRMS).

Secondary Outcome(s)

Secondary end point(s): -Brain atrophy as defined by the percent change in brain volume from baseline to month 15

-The time to first confirmed relapse during Period 1.

Timepoint(s) of evaluation of this end point: In terms of brain atrophy:

evaulation at baseline and at month 15

In terms relapse evaluation:

Evaluation will be done at each timepoint during the study once any symptoms suggestive of a relapse appear / are reported by any subject.

Secondary ID(s)

2012-003647-30-BE

LAQ-MS-305

Source(s) of Monetary Support

Teva Pharmaceutical Industries Ltd