Study Title: A multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, to evaluate the safety, tolerability and efficacy of daily oral administration of laquinimod 0.6 mg in subjects with relapsing remitting multiple sclerosis (RRMS) - Allegro

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-003226-19-HU
• Date of registration: 13/07/2007
• Prospective Registration: Yes
• Primary sponsor: Teva Pharmaceutical Industries Ltd
• Public title: Study Title: A multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, to evaluate the safety, tolerability and efficacy of daily oral administration of laquinimod 0.6 mg in subjects with relapsing remitting multiple sclerosis (RRMS) - Allegro
• Scientific title: Study Title: A multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, to evaluate the safety, tolerability and efficacy of daily oral administration of laquinimod 0.6 mg in subjects with relapsing remitting multiple sclerosis (RRMS) - Allegro
• Date of first enrolment: 09/10/2007
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003226-19
• 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: yes Other trial design description: an open label extension is foreseen If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Bulgaria, Czech Republic, Estonia, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course.
2. Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
3. Subjects must be in a stable neurological condition and free of corticosteroid treatment [intravenous (iv), intramuscular (im) and/or per os (po)] 30 days prior to screening (month -1).
4. Subjects must have had experienced one of the following:
? At least one documented relapse in the 12 months prior to screening
? At least two documented relapses in the 24 months prior to screening
? One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
5. Subjects must be between 18 and 55 years of age, inclusive.
6. Subjects must have disease duration of at least 6 months (from the first symptom) prior to screening.
7. Women of child-bearing potential must practice an acceptable methods of birth control [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner’s vasectomy or double-barrier method (condom or diaphragm with spermicide).
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
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. An onset of relapse, unstable neurological condition or any treatment with corticosteroids [intravenous (iv), intramuscular (im) and/or per os (po)] or ACTH between month -1 (screening) and 0 (baseline).
3. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
4. Use of immunosuppressive including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
5. Previous use of either of the following: natalizumab (Tysabri®), cladribine, laquinimod.
6. Previous treatment with glatiramer acetate (Copaxone®) Interferon-ß (either 1a or 1b) or IVIG within 2 months prior to screening visit.
7. Systemic corticosteroid treatment of =30 consecutive days duration within 2 months prior to screening visit.
8. Previous total body irradiation or total lymphoid irradiation.
9. Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
10. A known history of tuberculosis.
11. Acute infection two weeks prior to baseline visit.
12. Major trauma or surgery two weeks prior to baseline
13. A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
14. A carrier state of factor V Leiden mutation (either homo- or heterozygous) as disclosed at screening.
15. Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
16. Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine) see detailed list in Appendix 5
17. Use of amiodarone within 2 years prior to screening visit.
18. Pregnancy or breastfeeding.
19. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:
? A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.
? A gastrointestinal disorder that may affect the absorption of study medication.
? Renal or metabolic diseases.
? Any form of chronic liver disease, including known non-alcoholic steatohepatitis.
? A =2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin
? A QTC interval (obtained from either 2 ECG recordings at screening or from the mean value calculated from 3 measurements at baseline visit) which is >450msec.
? A family history of Long- QT syndrome.
? A history of drug and/or alcohol abuse.
? Major psychiatric disorder.
20. A known history of sensitivity to Gd.
21. Inability to successfully undergo MRI scanning.
22. Known drug hypersensitivity that would preclude administration of laquinimod, 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 (RRMS)
MedDRA version: 9.1 Level: PT Classification code 10028245 Term: Multiple sclerosis

Intervention(s)

Product Name: Laquinimod Capsules 0.6 mg
Product Code: TV-5600
Pharmaceutical Form: Capsule*
INN or Proposed INN: laquinimod
CAS Number: 248282-07-7
Current Sponsor code: TV-5600
Other descriptive name: ABR-215062 sodium salt
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.6-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Accumulation of physical disability measured by the time to confirmed
progression of EDSS during the double blind study period (A confirmed
progression of EDSS is defined as a 1 point increase from baseline on EDSS
score if baseline EDSS was between 0 and 5.0, or a 0.5 point increase if
baseline EDSS was 5.5, confirmed 3 months later. Progression can not be
confirmed during a relapse). EDSS changes relate to converted EDSS scores.
! To asses the cumulative number of enhancing lesions on T1-weighted images
taken on months 12, and 24 (and 30 in case of extending the study for 6 months).
! To asses the cumulative number of new hypointense lesions on enhanced T1
scans at months 12, and 24 (and 30 in case of extending the study for 6 months).
! To asses the cumulative number of new T2 lesions on scans taken on months 12
and 24 (and 30 in case of extending the study for 6 months).

Main Objective: To assess the efficacy of 0.6 mg daily dose of laquinimod compared to placebo in RRMS subjects, as measured by the number of confirmed relapses during the core study period.

Primary end point(s): The study's primary endpoint is the number of confirmed relapses during the double blind treatment phase.

Secondary ID(s)

2007-003226-19-NL

MS-LAQ-301