Safety and Efficacy of Orally Administered Laquinimod Versus Placebo for Treatment of Relapsing Remitting Multiple Sclerosis (RRMS)

NCT00509145 | Completed Phase 3 Results DMC

• 2 other identifiers: MS-LAQ-301EUDRACT 2007-003226-19
• Study Type: interventional
• Target: 1,106
• Locations: 22 countries
• Sites: 140

Brief Summary

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).

Conditions

Multiple Sclerosis

Keywords

Relapsing; Remitting

Outcome Measures

Primary Outcomes (1)

• Relapse Rate: Number of Confirmed Relapses During the Double Blind Study Period

  A relapse was defined as the appearance of at least one new neurological abnormality or the reappearance of at least one previously observed neurological abnormalities lasting greater than or equal to 48 hours and immediately preceded by an improving neurological state of greater than or equal to 30 days from onset of previous relapse. An event was counted as a relapse only when the participant's symptoms were accompanied by observed objective neurological changes, consistent with one or more of the following: An increase of greater than or equal to 0.5 in the Expanded Disability Status Scale (EDSS) score as compared to previous evaluation, an increase of one grade in the actual score of greater than or equal to 2 of the 7 functional systems (FS), as compared to previous evaluation, or an increase of 2 grades in the actual score of one FS as compared to the previous evaluation.

  Up to Month 24

Secondary Outcomes (4)

• Composite Endpoint: Sum of the Number of T1 Gadolinium (Gd)-Enhanced Lesions on T1-Weighted MRI Images

  Month 12, Month 24

• Composite Endpoint: Sum of the Number of New/Enlarging T2 Lesions

  Month 12, Month 24

• Accumulation of Physical Disability Measured by the Time to Confirmed Progression of Expanded Disability Status Scale (EDSS)

  Baseline to Month 24

• Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score

  Baseline, Month 24

Study Arms (2)

Laquinimod

EXPERIMENTAL

Laquinimod 0.6 mg, oral

Drug: Laquinimod

Placebo

PLACEBO COMPARATOR

Matching placebo

Other: Placebo

Interventions

Laquinimod DRUG

Laquinimod 0.6 mg capsule, oral, once daily

Also known as: TV-5600

Laquinimod

Placebo OTHER

oral, once daily, capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (144)

Teva Investigational Site 1076

Phoenix, Arizona, 85004, United States

Location

Teva Investigational Site 1090

Centennial, Colorado, 80112, United States

Location

Teva Investigational Site 1088

Fort Collins, Colorado, 80528, United States

Location

Teva Investigational Site 1094

New Haven, Connecticut, 06520-8018, United States

Location

Teva Investigational Site 1102

Northbrook, Illinois, 60062, United States

Location

Teva Investigational Site 1081

Fort Wayne, Indiana, 46805, United States

Location

Teva Investigational Site 1083

Des Moines, Iowa, 50314, United States

Location

Teva Investigational Site 1086

Kansas City, Kansas, 66160, United States

Location

Teva Investigational Site 1101

Lexington, Kentucky, 40513, United States

Location

Teva Investigational Site 1096

Farmington Hills, Michigan, 48334, United States

Location

Teva Investigational Site 1093

Minneapolis, Minnesota, 55414, United States

Location

Teva Investigational Site 1098

St Louis, Missouri, 63104, United States

Location

Teva Investigational Site 1082

New York, New York, 10003, United States

Location

Teva Investigational Site 1079

Rochester, New York, 14642, United States

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Teva Investigational Site 1073

Winston-Salem, North Carolina, 27157, United States

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Teva Investigational Site 1097

Fargo, North Dakota, 58103, United States

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Teva Investigational Site 1084

Dayton, Ohio, 45417, United States

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Teva Investigational Site 1092

Oklahoma City, Oklahoma, 73120, United States

Location

Teva Investigational Site 1100

Hershey, Pennsylvania, 17033-0850, United States

Location

Teva Investigational Site 1087

Philadelphia, Pennsylvania, 19104, United States

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Teva Investigational Site 1075

Lubbock, Texas, 79410, United States

Location

Teva Investigational Site 1078

San Antonio, Texas, 78231, United States

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Teva Investigational Site 1085

Milwaukee, Wisconsin, 53215, United States

Location

Teva Investigational Site 3300

Klagenfurt, 9020, Austria

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Teva Investigational Site 3303

Linz, A-4021, Austria

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Teva Investigational Site 3302

Sankt Pölten, 3100, Austria

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Teva Investigational Site 3301

Villach, 9500, Austria

Location

Teva Investigational Site 5901

Pleven, 5800, Bulgaria

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Teva Investigational Site 5904

Sofia, 1113, Bulgaria

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Teva Investigational Site 5903

Sofia, 1309, Bulgaria

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Teva Investigational Site 5900

Sofia, 1606, Bulgaria

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Teva Investigational Site 5905

Sofia, 1606, Bulgaria

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Teva Investigational Site 5902

Varna, 9010, Bulgaria

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Teva Investigational Site 1132

Halifax, Nova Scotia, B3M 0A6, Canada

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Teva Investigational Site 1126

London, Ontario, N6A 5A5, Canada

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Teva Investigational Site 1128

Ottawa, Ontario, K2G 6E2, Canada

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Teva Investigational Site 1134

Toronto, Ontario, M4N 3M5, Canada

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Teva Investigational Site 1130

Greenfield Park, Quebec, J4V 2J2, Canada

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Teva Investigational Site 1129

Montreal, Quebec, H1T 2M4, Canada

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Teva Investigational Site 1131

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Teva Investigational Site 5417

Olomouc, 779 00, Czechia

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Teva Investigational Site 5416

Ostrava - Poruba, 708 52, Czechia

Location

Teva Investigational Site 5504

Tallinn, EE-10617, Estonia

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Teva Investigational Site 5505

Tartu, EE-51014, Estonia

Location

Teva Investigational Site 3525

Besançon, 25030, France

Location

Teva Investigational Site 3527

Bron, 69677, France

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Teva Investigational Site 3526

Clermont-Ferrand, 63003, France

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Teva Investigational Site 3524

Lille, 59037, France

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Teva Investigational Site 3528

Marseille, 13385, France

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Teva Investigational Site 3529

Rennes, 35033, France

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Teva Investigational Site 8100

Tbilisi, 0112, Georgia

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Teva Investigational Site 8101

Tbilisi, 0179, Georgia

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Teva Investigational Site 3247

Bayreuth, 95445, Germany

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Teva Investigational Site 3241

Berlin, 10713, Germany

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Teva Investigational Site 3238

Berlin, 13347, Germany

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Teva Investigational Site 3248

Bochum, 44791, Germany

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Teva Investigational Site 3245

Dresden, 01307, Germany

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Teva Investigational Site 3237

Emden, 26721, Germany

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Teva Investigational Site 3242

Erbach im Odenwald, 64711, Germany

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Teva Investigational Site 3240

Erfurt, 99089, Germany

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Teva Investigational Site 3249

Freiburg im Breisgau, 79106, Germany

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Teva Investigational Site 3236

Hamburg, 20246, Germany

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Teva Investigational Site 3246

Hamburg, 22417, Germany

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Teva Investigational Site 3239

Hanover, 30559, Germany

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Teva Investigational Site 3243

Heidelberg, 69120, Germany

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Teva Investigational Site 3251

Münster, 48149, Germany

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Teva Investigational Site 3250

Trier, 54292, Germany

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Teva Investigational Site 3244

Ulm, 89081, Germany

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Teva Investigational Site 5115

Budapest, H-1145, Hungary

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Teva Investigational Site 5114

Debrecen, 4043, Hungary

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Teva Investigational Site 5116

Miskolc, 3526, Hungary

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Teva Investigational Site 5117

Veszprém, H-8200, Hungary

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Teva Investigational Site 8034

Haifa, 31048, Israel

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Teva Investigational Site 8031

Haifa, 3436212, Israel

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Teva Investigational Site 8030

Jerusalem, 9112001, Israel

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Teva Investigational Site 8033

Ramat Gan, 5262160, Israel

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Teva Investigational Site 8032

Tel Aviv, 78278, Israel

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Teva Investigational Site 3044

Catania, 95122, Italy

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Teva Investigational Site 3045

Fidenza, 43036, Italy

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Teva Investigational Site 3042

Gallarate, 21013, Italy

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Teva Investigational Site 3046

Grosseto, 58100, Italy

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Teva Investigational Site 3047

Milan, 20122, Italy

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Teva Investigational Site 3038

Milan, 20132, Italy

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Teva Investigational Site 555

Milan, 20132, Italy

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Teva Investigational Site 3039

Milan, 20148, Italy

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Teva Investigational Site 3041

Palermo, 90146, Italy

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Teva Investigational Site 3040

Rome, 00133, Italy

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Teva Investigational Site 5604

Riga, 1015, Latvia

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Teva Investigational Site 5704

Kaunas, 50009, Lithuania

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Teva Investigational Site 5705

Šiauliai, 76231, Lithuania

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Teva Investigational Site 3809

Groesbeek, 6561 KE, Netherlands

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Teva Investigational Site 3810

Nieuwegein, 3430 EM, Netherlands

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Teva Investigational Site 3811

Tilburg, 5022 GC, Netherlands

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Teva Investigational Site 5322

Częstochowa, 42-200, Poland

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Teva Investigational Site 5319

Gmina Końskie, 26-200, Poland

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Teva Investigational Site 5320

Gorzów Wielkopolski, 66-400, Poland

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Teva Investigational Site 5316

Katowice, 40-752, Poland

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Teva Investigational Site 5318

Kielce, 25-736, Poland

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Teva Investigational Site 5317

Krakow, 31-826, Poland

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Teva Investigational Site 5315

Lodz, 90-153, Poland

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Teva Investigational Site 5325

Warsaw, 04-749, Poland

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Teva Investigational Site 5208

Bucharest, 011461, Romania

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Teva Investigational Site 5210

Cluj-Napoca, 400437, Romania

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Teva Investigational Site 5212

Constanța, 900123, Romania

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Teva Investigational Site 5211

Târgu Mureş, 540136, Romania

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Teva Investigational Site 5209

Timișoara, 300736, Romania

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Teva Investigational Site 5031

Kemerovo, 650066, Russia

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Teva Investigational Site 5021

Moscow, 127018, Russia

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Teva Investigational Site 5028

Nizhny Novgorod, 603126, Russia

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Teva Investigational Site 5027

Novosibirsk, 630087, Russia

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Teva Investigational Site 5030

Perm, 614990, Russia

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Teva Investigational Site 5026

Saint Petersburg, 191025, Russia

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Teva Investigational Site 5025

Saint Petersburg, 194044, Russia

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Teva Investigational Site 5024

Saint Petersburg, 194354, Russia

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Teva Investigational Site 5022

Saint Petersburg, 197022, Russia

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Teva Investigational Site 5023

Saint Petersburg, 197376, Russia

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Teva Investigational Site 5029

Yekaterinburg, 620102, Russia

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Teva Investigational Site 6100

Belgrade, 11000, Serbia

Location

Teva Investigational Site 6102

Niš, 18 000, Serbia

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Teva Investigational Site 3132

Barcelona, 08035, Spain

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Teva Investigational Site 3134

Barcelona, 08036, Spain

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Teva Investigational Site 3144

Barcelona, 08041, Spain

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Teva Investigational Site 3140

Beade-Vigo, 36312, Spain

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Teva Investigational Site 3142

Getafe, 28905, Spain

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Teva Investigational Site 3136

Girona, 17007, Spain

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Teva Investigational Site 3135

Lleida, 25198, Spain

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Teva Investigational Site 3133

Madrid, 28040, Spain

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Teva Investigational Site 3146

Madrid, 28046, Spain

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Teva Investigational Site 3137

Murcia, 30120, Spain

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Teva Investigational Site 3138

Pontevedra, 36001, Spain

Location

Teva Investigational Site 3139

Santiago de Compostela, 15706, Spain

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Teva Investigational Site 3143

Valencia, 46010, Spain

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Teva Investigational Site 4204

Stockholm, 14186, Sweden

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Teva Investigational Site 4205

Stockholm, 17176, Sweden

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Teva Investigational Site 4206

Stockholm, 18288, Sweden

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Teva Investigational Site 8201

Izmir, 35340, Turkey (Türkiye)

Location

Teva Investigational Site 5803

Dnipropetrovsk, 49027, Ukraine

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Teva Investigational Site 5802

Kyiv, 03110, Ukraine

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Teva Investigational Site 5804

Kyiv, 03115, Ukraine

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Teva Investigational Site 5800

Lviv, 79010, Ukraine

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Teva Investigational Site 5801

Vinnytsia, 21005, Ukraine

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Teva Investigational Site 3425

Liverpool, L9 7LJ, United Kingdom

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Teva Investigational Site 3424

London, E1 2AT, United Kingdom

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Teva Investigational Site 3422

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (3)

• Kolb-Sobieraj C, Gupta S, Weinstock-Guttman B. Laquinimod therapy in multiple sclerosis: a comprehensive review. Neurol Ther. 2014 May 6;3(1):29-39. doi: 10.1007/s40120-014-0017-6. eCollection 2014 Jun.

  PMID: 26000222 DERIVED

• Filippi M, Rocca MA, Pagani E, De Stefano N, Jeffery D, Kappos L, Montalban X, Boyko AN, Comi G; ALLEGRO Study Group. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):851-8. doi: 10.1136/jnnp-2013-306132. Epub 2013 Sep 12.

  PMID: 24029546 DERIVED

• Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, Filippi M; ALLEGRO Study Group. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012 Mar 15;366(11):1000-9. doi: 10.1056/NEJMoa1104318.

  PMID: 22417253 DERIVED

Related Links

• Teva's Allegro Clinical Trials website

MeSH Terms

Conditions

Multiple Sclerosis; Recurrence

Interventions

laquinimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Giancarlo Comi

  U.O.Neurology-Neurorehabilitation and Clinical Neurophysiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2007
• First Posted: July 31, 2007
• Study Start: November 13, 2007
• Primary Completion: November 8, 2010
• Study Completion: November 8, 2010
• Last Updated: November 2, 2021
• Results First Posted: November 2, 2021

Record last verified: 2021-09

Locations

UA (5); ES (13); LI (2); HU (4); TU (1); GE (2); DE (16); US (23); BU (6); SE (3); GB (3); IT (10); CZ (2); FR (6); AU (4); LA (1); NL (3); PL (8); IL (5); RO (5); CA (7); RU (11)