Safety and Efficacy of Orally Administered Laquinimod Versus Placebo for Treatment of Relapsing Remitting Multiple Sclerosis (RRMS) (ALLEGRO)
This study has been completed.
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
First received: July 27, 2007
Last updated: February 16, 2012
Last verified: February 2012
Determination the efficacy of daily oral treatment with laquinimod 0.6 mg capsules as compared to placebo in subjects with Relapsing Remitting Multiple Sclerosis (RRMS).
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||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)
Primary Outcome Measures:
- Relapse Rate: Number of confirmed relapses during the double blind study period. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Accumulation of physical disability measured by the time to confirmed progression of EDSS during the study period. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- MRI Outcomes [ Time Frame: 12, 24 months ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||November 2010 (Final data collection date for primary outcome measure)
Laquinimod 0.6 mg, oral
Laquinimod 0.6 mg capsule, oral, once daily
Other Name: TV-5600
Placebo Comparator: Placebo
oral, once daily, capsule
Other Name: placebo
|Ages Eligible for Study:
||18 Years to 55 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
- 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).
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.
- Subjects must be between 18 and 55 years of age, inclusive.
- Subjects must have disease duration of at least 6 months (from the first symptom) prior to screening.
- Women of child-bearing potential must practice an acceptable method 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).
- 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.
- Subjects with progressive forms of MS
- 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).
- Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
- Use of immunosuppressive including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
- Previous use of either of the following: natalizumab (Tysabri®), cladribine, laquinimod.
- Previous treatment with glatiramer acetate (Copaxone®) Interferon-β (either 1a or 1b) or IVIG within 2 months prior to screening visit.
- Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit.
- Previous total body irradiation or total lymphoid irradiation.
- Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
- A known history of tuberculosis.
- Acute infection two weeks prior to baseline visit.
- Major trauma or surgery two weeks prior to baseline
- A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
- A carrier state of factor V Leiden mutation (either homo- or heterozygous) as disclosed at screening.
- Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
- Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine) see detailed list in Appendix 5
- Use of amiodarone within 2 years prior to screening visit.
- Pregnancy or breastfeeding.
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.
- A known history of sensitivity to Gd.
- Inability to successfully undergo MRI scanning.
- Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.
- Subjects who suffer from any form of progressive MS.
- Any condition which the investigator feels may interfere with participation in the study.
- Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation,
- Subjects who received any investigational medication, immunosuppressives or cytotoxic agents within 6 months prior to screening
- Previous treatment with immunomodulators within two months prior to screening
- Pregnancy or breastfeeding.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00509145
Teva Pharmaceutical Industries
||U.O.Neurology-Neurorehabilitation and Clinical Neurophysiology
No publications provided by Teva Pharmaceutical Industries
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
||Teva Pharmaceutical Industries
History of Changes
|Other Study ID Numbers:
||MS-LAQ-301, EUDRACT 2007-003226-19
|Study First Received:
||July 27, 2007
||February 16, 2012
||United States: Food and Drug Administration
Austria : Federal Ministry for Labour, Health, and Social Affairs
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Estonia: The State Agency of Medicine
European Union: European Medicines Agency
France: Ministry of Health
Georgia: Ministry of Health
Germany: Ministry of Health
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Poland: Ministry of Health
Romania: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Bulgaria: Ministry of Health
Spain: Ministry of Health
Sweden: Medical Products Agency
Turkey: Ministry of Health
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Keywords provided by Teva Pharmaceutical Industries:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on June 17, 2013
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Immune System Diseases