A Study To Evaluate the Long-Term Safety, Tolerability and Effect on Disease Course

A Multinational, Multicenter, Open-label, Single-assignment Extension of the MS-LAQ-301 (ALLEGRO) Study, to Evaluate the Long-term Safety, Tolerability and Effect on Disease Course of Daily Oral Laquinimod 0.6 mg in Subjects With Relapsing MS

The purpose of this study is to make laquinimod 0.6 mg available for all subjects who completed the placebo-controlled MS-LAQ-301 study according to the protocol and to evaluate the long-term safety, tolerability and effect on disease course of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis.

Study Overview

• Status: Terminated
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Laquinimod

• Study Type: Interventional
• Enrollment (Actual): 839
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Klagenfurt, Austria, 9020
    • Teva Investigational Site 3300
  • Linz, Austria, A-4021
    • Teva Investigational Site 3303
  • Sankt Polten, Austria, 3100
    • Teva Investigational Site 3302
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Teva Investigational Site 5901
  • Sofia, Bulgaria, 1113
    • Teva Investigational Site 5904
  • Sofia, Bulgaria, 1309
    • Teva Investigational Site 5903
  • Sofia, Bulgaria, 1606
    • Teva Investigational Site 5900
  • Sofia, Bulgaria, 1606
    • Teva Investigational Site 5905
  • Varna, Bulgaria, 9010
    • Teva Investigational Site 5902
• Canada
  • Nova Scotia
    • Bedford, Nova Scotia, Canada, B4A 1A9
      • Teva Investigational Site 1132
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Teva Investigational Site 1126
    • Ottawa, Ontario, Canada, K2G 6E2
      • Teva Investigational Site 1128
    • Toronto, Ontario, Canada, M4N 3M5
      • Teva Investigational Site 1134
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Teva Investigational Site 1130
    • Montreal, Quebec, Canada, H1T 2M4
      • Teva Investigational Site 1129
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Teva Investigational Site 1131
• Czechia
  • Olomouc, Czechia, 779 00
    • Teva Investigational Site 5417
  • Ostrava - poruba, Czechia, 708 52
    • Teva Investigational Site 5416
• Estonia
  • Tallinn, Estonia, EE-10617
    • Teva Investigational Site 5504
  • Tartu, Estonia, EE-51014
    • Teva Investigational Site 5505
• France
  • Besancon, France, 25030
    • Teva Investigational Site 3525
  • Bron Cedex, France, 69677
    • Teva Investigational Site 3527
  • Clermont-Ferrand Cedex 1, France, 63003
    • Teva Investigational Site 3526
  • Lille Cedex, France, 59037
    • Teva Investigational Site 3524
  • Marseille Cedex 5, France, 13385
    • Teva Investigational Site 3528
  • Rennes Cedex 9, France, 35033
    • Teva Investigational Site 3529
• Georgia
  • Tbilisi, Georgia, 0112
    • Teva Investigational Site 8100
  • Tbilisi, Georgia, 0179
    • Teva Investigational Site 8101
• Germany
  • Bayreuth, Germany, 95445
    • Teva Investigational Site 3247
  • Berlin, Germany, 10713
    • Teva Investigational Site 3241
  • Berlin, Germany, 13347
    • Teva Investigational Site 3238
  • Bochum, Germany, 44791
    • Teva Investigational Site 3248
  • Dresden, Germany, 01307
    • Teva Investigational Site 3245
  • Emden, Germany, 26721
    • Teva Investigational Site 3237
  • Erbach, Germany, 64711
    • Teva Investigational Site 3242
  • Erfurt, Germany, 99089
    • Teva Investigational Site 3240
  • Freiburg, Germany, 79106
    • Teva Investigational Site 3249
  • Hamburg, Germany, 20246
    • Teva Investigational Site 3236
  • Hamburg, Germany, 22417
    • Teva Investigational Site 3246
  • Hannover, Germany, 30171
    • Teva Investigational Site 3239
  • Heidelberg, Germany, 69120
    • Teva Investigational Site 3243
  • Munster, Germany, 48149
    • Teva Investigational Site 3251
  • Trier, Germany, 54292
    • Teva Investigational Site 3250
  • Ulm, Germany, 89081
    • Teva Investigational Site 3244
• Hungary
  • Budapest, Hungary, H-1145
    • Teva Investigational Site 5115
  • Debrecen, Hungary, 4043
    • Teva Investigational Site 5114
  • Miskolc, Hungary, 3526
    • Teva Investigational Site 5116
  • Veszprem, Hungary, H-8200
    • Teva Investigational Site 5117
• Israel
  • Haifa, Israel, 3436212
    • Teva Investigational Site 8031
  • Jerusalem, Israel, 9112001
    • Teva Investigational Site 8030
  • Ramat Gan, Israel, 5262160
    • Teva Investigational Site 8033
  • Tel Aviv, Israel, 78278
    • Teva Investigational Site 8032
• Italy
  • Catania, Italy, 95124
    • Teva Investigational Site 3044
  • Fidenza, Italy, 43036
    • Teva Investigational Site 3045
  • Gallarate, Italy, 21013
    • Teva Investigational Site 3042
  • Grosseto, Italy, 58100
    • Teva Investigational Site 3046
  • Milano, Italy, 20132
    • Teva Investigational Site 3038
  • Milano, Italy, 20132
    • Teva Investigational Site 555
  • Milano, Italy, 20148
    • Teva Investigational Site 3039
  • Palermo, Italy, 90146
    • Teva Investigational Site 3041
  • Rome, Italy, 00133
    • Teva Investigational Site 3040
• Lithuania
  • Kaunas, Lithuania, 50009
    • Teva Investigational Site 5704
  • Siauliai, Lithuania, 76231
    • Teva Investigational Site 5705
• Netherlands
  • Nieuwegein, Netherlands, 3430 EM
    • Teva Investigational Site 3810
  • Nijmegen, Netherlands, 6525 GC
    • Teva Investigational Site 3809
• Poland
  • Czestochowa, Poland, 42-280
    • Teva Investigational Site 5322
  • Gorzow Wielkopolski, Poland, 66-400
    • Teva Investigational Site 5320
  • Katowice, Poland, 40-752
    • Teva Investigational Site 5316
  • Kielce, Poland, 25-726
    • Teva Investigational Site 5318
  • Konskie, Poland, 26-200
    • Teva Investigational Site 5319
  • Krakow, Poland, 31-826
    • Teva Investigational Site 5317
  • Lodz, Poland, 90-153
    • Teva Investigational Site 5315
  • Warszawa, Poland, 04-749
    • Teva Investigational Site 5325
• Romania
  • Bucharest, Romania, 011461
    • Teva Investigational Site 5208
  • Cluj-Napoca, Romania, 400437
    • Teva Investigational Site 5210
  • Constanta, Romania, 900123
    • Teva Investigational Site 5212
  • Targu-Mures, Romania, 540136
    • Teva Investigational Site 5211
  • Timisoara, Romania, 300736
    • Teva Investigational Site 5209
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Teva Investigational Site 5029
  • Moscow, Russian Federation, 127015
    • Teva Investigational Site 5021
  • Nizhny Novgorod, Russian Federation, 603126
    • Teva Investigational Site 5028
  • Novosibirsk, Russian Federation, 630087
    • Teva Investigational Site 5027
  • Perm, Russian Federation, 614990
    • Teva Investigational Site 5030
  • Saint Petersburg, Russian Federation, 197022
    • Teva Investigational Site 5022
  • St. Petersburg, Russian Federation, 194044
    • Teva Investigational Site 5025
  • St. Petersburg, Russian Federation, 194354
    • Teva Investigational Site 5024
  • St. Petersburg, Russian Federation, 197376
    • Teva Investigational Site 5023
  • St.Petersburg, Russian Federation, 191186
    • Teva Investigational Site 5026
• Serbia
  • Belgrade, Serbia, 11000
    • Teva Investigational Site 6100
  • Nis, Serbia, 18 000
    • Teva Investigational Site 6102
• Spain
  • Barcelona, Spain, 08035
    • Teva Investigational Site 3132
  • Barcelona, Spain, 08036
    • Teva Investigational Site 3134
  • Barcelona, Spain, 08041
    • Teva Investigational Site 3144
  • Beade-Pontevedra, Spain, 36312
    • Teva Investigational Site 3140
  • Getafe, Spain, 28905
    • Teva Investigational Site 3142
  • Lleida, Spain, 25198
    • Teva Investigational Site 3135
  • Madrid, Spain, 28040
    • Teva Investigational Site 3133
  • Madrid, Spain, 28046
    • Teva Investigational Site 3146
  • Murcia, Spain, 30120
    • Teva Investigational Site 3137
  • Pontevedra, Spain, 36001
    • Teva Investigational Site 3138
  • Salt, Spain, 17190
    • Teva Investigational Site 3136
  • Santiago de Compostela, Spain, 15706
    • Teva Investigational Site 3139
  • Valencia, Spain, 46010
    • Teva Investigational Site 3143
• Sweden
  • Stockholm, Sweden, 14186
    • Teva Investigational Site 4204
  • Stockholm, Sweden, 17176
    • Teva Investigational Site 4205
  • Stockholm, Sweden, 18288
    • Teva Investigational Site 4206
• Turkey
  • Izmir, Turkey, 35340
    • Teva Investigational Site 8201
• Ukraine
  • Dnipropetrovsk, Ukraine, 49027
    • Teva Investigational Site 5803
  • Kyiv, Ukraine, 03110
    • Teva Investigational Site 5802
  • Kyiv, Ukraine, 03115
    • Teva Investigational Site 5804
  • Lviv, Ukraine, 79010
    • Teva Investigational Site 5800
  • Vinnytsya, Ukraine, 21005
    • Teva Investigational Site 5801
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
    • Teva Investigational Site 3425
  • London, United Kingdom, E1 2AT
    • Teva Investigational Site 3424
  • Sheffield, United Kingdom, S10 2JF
    • Teva Investigational Site 3422
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Teva Investigational Site 1076
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Teva Investigational Site 1090
    • Fort Collins, Colorado, United States, 80528
      • Teva Investigational Site 1088
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Teva Investigational Site 1102
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Teva Investigational Site 1081
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Teva Investigational Site 1083
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Teva Investigational Site 1086
  • Kentucky
    • Lexington, Kentucky, United States, 40513
      • Teva Investigational Site 1101
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Teva Investigational Site 1096
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Teva Investigational Site 1093
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Teva Investigational Site 1098
  • New York
    • New York, New York, United States, 10016
      • Teva Investigational Site 1082
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Teva Investigational Site 1073
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Teva Investigational Site 1097
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Teva Investigational Site 1084
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Teva Investigational Site 1092
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Teva Investigational Site 1100
  • Texas
    • Lubbock, Texas, United States, 79410
      • Teva Investigational Site 1075
    • San Antonio, Texas, United States, 78231
      • Teva Investigational Site 1078
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Teva Investigational Site 1085

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must have completed the Termination visit of MS-LAQ-301 (completion of all Termination visit activities) according to the MS-LAQ-301 protocol.
2. Women of child-bearing potential must practice an acceptable method of birth control [acceptable methods of birth control in this open label extension phase include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch (or hormone-releasing vaginal ring), long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)] during the study and up to 30 days after the last dose of the study drug..
3. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.
4. Subjects must be able to comprehend, sign and date a written informed consent prior to entering the MS-LAQ-301E study.

Exclusion Criteria:

1. Premature discontinuation from the MS-LAQ-301 study, for any reason.
2. Pregnancy [according to urine dipstick β-HCG test performed at Baseline (Month 0E) visit] or breastfeeding.
3. Subjects with clinically significant or unstable medical or surgical condition detected or worsened during the MS-LAQ-301 study, which preclude safe participation and completion of the MS-LAQ-301E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-301E study.
4. Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (V0E, Month 0E).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laquinimod; One capsule containing 0.6 mg laquinimod to be administered orally once daily.	Drug: Laquinimod; One capsule containing 0.6 mg laquinimod to be administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Treatment-Emergent Adverse Events (TEAEs)	A treatment-emergent adverse event was defined as any untoward medical occurrence that develops or worsens in severity following start of treatment and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs (SAE) include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. TEAEs associated with cancer, ischemic heart disease, cerebrovascular events, and arthritis were considered to be of special interest.	Day 1 up to 7.64 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Potentially Clinically Significant Abnormal Vital Signs	Vital signs with potentially clinically significant abnormal results were evaluated using the following significance criteria: Pulse rate low: <=45 and decrease >=30 beats/minute; Pulse rate high: >=120 and increase >=30 beats/minute; Systolic blood pressure low: <=90 and decrease >=30 mmHg; Systolic blood pressure high: >=180 and increase >=30 mmHg; Diastolic blood pressure low: <=50 and decrease >=20 mmHg; Diastolic blood pressure high: >=100 and increase >=20 mmHg	Day 1 up to 7.64 years
Participants With Serum Chemistry Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study	Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study; a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non- PCS value are included in the population count. ALT=alanine aminotransferase ALP=alkaline phosphatase P-amylase=amylase, pancreatic AST=aspartate aminotransferase CRP=C reactive protein CK=creatine kinase CTN=creatinine FIB=fibrinogen GGT=gamma glutamyl transferase K=potassium	Day 1 up to 7.64 years
Participants With Serum Hematology Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study	Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study; a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non- PCS value are included in the population count.	Day 1 up to 7.64 years
Participants With Electrocardiogram (ECG) Fiindings That Shifted From Baseline to Any Time During the Study	Shifts are presented as Baseline finding / Worse finding at anytime during the study. Categories for findings are: normal; abnormal, not clinically significant (Not CS); abnormal, clinically significant (CS)	Day 1 up to 7.64 years

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Principal Investigator: Giancarlo Comi, Prof., MD, U.O.Neurology-Neurorehabilitation and Clinical Neurophysiology

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2009
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: September 28, 2009
• First Submitted That Met QC Criteria: September 30, 2009
• First Posted (Estimate): October 1, 2009

Study Record Updates

• Last Update Posted (Actual): December 9, 2021
• Last Update Submitted That Met QC Criteria: December 7, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Relapsing Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Multiple Sclerosis; Sclerosis; Disease Progression
• Other Study ID Numbers: MS-LAQ-301E; 2009-012989-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No