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

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00509145
Collaborator
(none)
1,106
Enrollment
144
Locations
2
Arms
35.8
Actual Duration (Months)
7.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1106 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official 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 RRMS
Actual Study Start Date :
Nov 13, 2007
Actual Primary Completion Date :
Nov 8, 2010
Actual Study Completion Date :
Nov 8, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Laquinimod

Laquinimod 0.6 mg, oral

Drug: Laquinimod
Laquinimod 0.6 mg capsule, oral, once daily
Other Names:
  • TV-5600

    		•
    Placebo Comparator: Placebo

    Matching placebo

    Other: Placebo
    oral, once daily, capsule

    Outcome Measures

    Primary Outcome Measures

    1. Relapse Rate: Number of Confirmed Relapses During the Double Blind Study Period [Up to Month 24]

      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.

    Secondary Outcome Measures

    1. Composite Endpoint: Sum of the Number of T1 Gadolinium (Gd)-Enhanced Lesions on T1-Weighted MRI Images [Month 12, Month 24]

      Composite score was calculated as the sum of the number of gadolinium (Gd)-enhanced lesions at Month 12 and the number of gadolinium (Gd)-enhanced lesions at Month 24 on T1-Weighted MRI scans.

    2. Composite Endpoint: Sum of the Number of New/Enlarging T2 Lesions [Month 12, Month 24]

      Composite score calculated as the sum of T2 lesions at Months 12 and 24 that are new or enlarged.

    3. Accumulation of Physical Disability Measured by the Time to Confirmed Progression of Expanded Disability Status Scale (EDSS) [Baseline to Month 24]

      EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). A confirmed progression of EDSS is defined as at least 1 point increase from baseline if baseline EDSS was between 0 and 5.0, or at least 0.5 point increase if baseline EDSS was 5.5 or higher, confirmed 3 months later. Participants were assessed between baseline and month 24 visit. Participants that met these criteria for any 3 consecutive months were counted in the progression category. Progression could not be confirmed during an MS relapse. Data is presented as a distribution of confirmed disease progression (CDP) events (number of participants with CDP).

    4. Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score [Baseline, Month 24]

      The Multiple Sclerosis Functional Composite is an instrument assessing disability that consists of 3 clinical assessments. The 3 are Timed 25-Foot Walk, 9-Hole Peg Test which measures upper extremity (arm and hand) function, and PASAT (Paced Auditory Serial Addition Test) which is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. A Z-score is used to define a common metric from the 3 assessments that constitute the MSFC score. The study's population at baseline was used as reference population for the Z-score calculation. A Z-score of 0 represents the population mean at baseline. Higher Z-scores correspond to an improved outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. Subjects must be between 18 and 55 years of age, inclusive.

    2. Subjects must have disease duration of at least 6 months (from the first symptom) prior to screening.

    3. 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).

    4. Subjects must be able to sign and date a written informed consent prior to entering the study

    5. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

    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-β (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.

    1. A known history of sensitivity to Gd.

    2. Inability to successfully undergo MRI scanning.

    3. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.

    Exclusion Criteria:

    1. Subjects who suffer from any form of progressive MS.

    2. Any condition which the investigator feels may interfere with participation in the study.

    3. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation,

    4. Subjects who received any investigational medication, immunosuppressives or cytotoxic agents within 6 months prior to screening

    5. Previous treatment with immunomodulators within two months prior to screening

    6. Pregnancy or breastfeeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Teva Investigational Site 1076 Phoenix Arizona United States 85004
    2 Teva Investigational Site 1090 Centennial Colorado United States 80112
    3 Teva Investigational Site 1088 Fort Collins Colorado United States 80528
    4 Teva Investigational Site 1094 New Haven Connecticut United States 06520-8018
    5 Teva Investigational Site 1102 Northbrook Illinois United States 60062
    6 Teva Investigational Site 1081 Fort Wayne Indiana United States 46805
    7 Teva Investigational Site 1083 Des Moines Iowa United States 50314
    8 Teva Investigational Site 1086 Kansas City Kansas United States 66160
    9 Teva Investigational Site 1101 Lexington Kentucky United States 40513
    10 Teva Investigational Site 1096 Farmington Hills Michigan United States 48334
    11 Teva Investigational Site 1093 Minneapolis Minnesota United States 55414
    12 Teva Investigational Site 1098 Saint Louis Missouri United States 63104
    13 Teva Investigational Site 1082 New York New York United States 10003
    14 Teva Investigational Site 1079 Rochester New York United States 14642
    15 Teva Investigational Site 1073 Winston-Salem North Carolina United States 27157
    16 Teva Investigational Site 1097 Fargo North Dakota United States 58103
    17 Teva Investigational Site 1084 Dayton Ohio United States 45417
    18 Teva Investigational Site 1092 Oklahoma City Oklahoma United States 73120
    19 Teva Investigational Site 1100 Hershey Pennsylvania United States 17033-0850
    20 Teva Investigational Site 1087 Philadelphia Pennsylvania United States 19104
    21 Teva Investigational Site 1075 Lubbock Texas United States 79410
    22 Teva Investigational Site 1078 San Antonio Texas United States 78231
    23 Teva Investigational Site 1085 Milwaukee Wisconsin United States 53215
    24 Teva Investigational Site 3300 Klagenfurt Austria 9020
    25 Teva Investigational Site 3303 Linz Austria A-4021
    26 Teva Investigational Site 3302 Sankt Polten Austria 3100
    27 Teva Investigational Site 3301 Villach Austria 9500
    28 Teva Investigational Site 5901 Pleven Bulgaria 5800
    29 Teva Investigational Site 5904 Sofia Bulgaria 1113
    30 Teva Investigational Site 5903 Sofia Bulgaria 1309
    31 Teva Investigational Site 5900 Sofia Bulgaria 1606
    32 Teva Investigational Site 5905 Sofia Bulgaria 1606
    33 Teva Investigational Site 5902 Varna Bulgaria 9010
    34 Teva Investigational Site 1132 Halifax Nova Scotia Canada B3M 0A6
    35 Teva Investigational Site 1126 London Ontario Canada N6A 5A5
    36 Teva Investigational Site 1128 Ottawa Ontario Canada K2G 6E2
    37 Teva Investigational Site 1134 Toronto Ontario Canada M4N 3M5
    38 Teva Investigational Site 1130 Greenfield Park Quebec Canada J4V 2J2
    39 Teva Investigational Site 1129 Montreal Quebec Canada H1T 2M4
    40 Teva Investigational Site 1131 Sherbrooke Quebec Canada J1H 5N4
    41 Teva Investigational Site 5417 Olomouc Czechia 779 00
    42 Teva Investigational Site 5416 Ostrava - poruba Czechia 708 52
    43 Teva Investigational Site 5504 Tallinn Estonia EE-10617
    44 Teva Investigational Site 5505 Tartu Estonia EE-51014
    45 Teva Investigational Site 3525 Besancon France 25030
    46 Teva Investigational Site 3527 Bron Cedex France 69677
    47 Teva Investigational Site 3526 Clermont-Ferrand Cedex 1 France 63003
    48 Teva Investigational Site 3524 Lille Cedex France 59037
    49 Teva Investigational Site 3528 Marseille Cedex 5 France 13385
    50 Teva Investigational Site 3529 Rennes Cedex 9 France 35033
    51 Teva Investigational Site 8100 Tbilisi Georgia 0112
    52 Teva Investigational Site 8101 Tbilisi Georgia 0179
    53 Teva Investigational Site 3247 Bayreuth Germany 95445
    54 Teva Investigational Site 3241 Berlin Germany 10713
    55 Teva Investigational Site 3238 Berlin Germany 13347
    56 Teva Investigational Site 3248 Bochum Germany 44791
    57 Teva Investigational Site 3245 Dresden Germany 01307
    58 Teva Investigational Site 3237 Emden Germany 26721
    59 Teva Investigational Site 3242 Erbach Germany 64711
    60 Teva Investigational Site 3240 Erfurt Germany 99089
    61 Teva Investigational Site 3249 Freiburg Germany 79106
    62 Teva Investigational Site 3236 Hamburg Germany 20246
    63 Teva Investigational Site 3246 Hamburg Germany 22417
    64 Teva Investigational Site 3239 Hannover Germany 30559
    65 Teva Investigational Site 3243 Heidelberg Germany 69120
    66 Teva Investigational Site 3251 Munster Germany 48149
    67 Teva Investigational Site 3250 Trier Germany 54292
    68 Teva Investigational Site 3244 Ulm Germany 89081
    69 Teva Investigational Site 5115 Budapest Hungary H-1145
    70 Teva Investigational Site 5114 Debrecen Hungary 4043
    71 Teva Investigational Site 5116 Miskolc Hungary 3526
    72 Teva Investigational Site 5117 Veszprem Hungary H-8200
    73 Teva Investigational Site 8034 Haifa Israel 31048
    74 Teva Investigational Site 8031 Haifa Israel 3436212
    75 Teva Investigational Site 8030 Jerusalem Israel 9112001
    76 Teva Investigational Site 8033 Ramat Gan Israel 5262160
    77 Teva Investigational Site 8032 Tel Aviv Israel 78278
    78 Teva Investigational Site 3044 Catania Italy 95122
    79 Teva Investigational Site 3045 Fidenza Italy 43036
    80 Teva Investigational Site 3042 Gallarate Italy 21013
    81 Teva Investigational Site 3046 Grosseto Italy 58100
    82 Teva Investigational Site 3047 Milano Italy 20122
    83 Teva Investigational Site 3038 Milano Italy 20132
    84 Teva Investigational Site 555 Milano Italy 20132
    85 Teva Investigational Site 3039 Milano Italy 20148
    86 Teva Investigational Site 3041 Palermo Italy 90146
    87 Teva Investigational Site 3040 Rome Italy 00133
    88 Teva Investigational Site 5604 Riga Latvia 1015
    89 Teva Investigational Site 5704 Kaunas Lithuania 50009
    90 Teva Investigational Site 5705 Siauliai Lithuania 76231
    91 Teva Investigational Site 3809 Groesbeek Netherlands 6561 KE
    92 Teva Investigational Site 3810 Nieuwegein Netherlands 3430 EM
    93 Teva Investigational Site 3811 Tilburg Netherlands 5022 GC
    94 Teva Investigational Site 5322 Czestochowa Poland 42-200
    95 Teva Investigational Site 5320 Gorzow Wielkopolski Poland 66-400
    96 Teva Investigational Site 5316 Katowice Poland 40-752
    97 Teva Investigational Site 5318 Kielce Poland 25-736
    98 Teva Investigational Site 5319 Konskie Poland 26-200
    99 Teva Investigational Site 5317 Krakow Poland 31-826
    100 Teva Investigational Site 5315 Lodz Poland 90-153
    101 Teva Investigational Site 5325 Warszawa Poland 04-749
    102 Teva Investigational Site 5208 Bucharest Romania 011461
    103 Teva Investigational Site 5210 Cluj-Napoca Romania 400437
    104 Teva Investigational Site 5212 Constanta Romania 900123
    105 Teva Investigational Site 5211 Targu-Mures Romania 540136
    106 Teva Investigational Site 5209 Timisoara Romania 300736
    107 Teva Investigational Site 5029 Ekaterinburg Russian Federation 620102
    108 Teva Investigational Site 5031 Kemerovo Russian Federation 650066
    109 Teva Investigational Site 5021 Moscow Russian Federation 127018
    110 Teva Investigational Site 5028 Nizhny Novgorod Russian Federation 603126
    111 Teva Investigational Site 5027 Novosibirsk Russian Federation 630087
    112 Teva Investigational Site 5030 Perm Russian Federation 614990
    113 Teva Investigational Site 5022 Saint Petersburg Russian Federation 197022
    114 Teva Investigational Site 5026 Saint-Petersburg Russian Federation 191025
    115 Teva Investigational Site 5025 St. Petersburg Russian Federation 194044
    116 Teva Investigational Site 5024 St. Petersburg Russian Federation 194354
    117 Teva Investigational Site 5023 St. Petersburg Russian Federation 197376
    118 Teva Investigational Site 6100 Belgrade Serbia 11000
    119 Teva Investigational Site 6102 Nis Serbia 18 000
    120 Teva Investigational Site 3132 Barcelona Spain 08035
    121 Teva Investigational Site 3134 Barcelona Spain 08036
    122 Teva Investigational Site 3144 Barcelona Spain 08041
    123 Teva Investigational Site 3140 Beade-Vigo Spain 36312
    124 Teva Investigational Site 3142 Getafe Spain 28905
    125 Teva Investigational Site 3136 Girona Spain 17007
    126 Teva Investigational Site 3135 Lleida Spain 25198
    127 Teva Investigational Site 3133 Madrid Spain 28040
    128 Teva Investigational Site 3146 Madrid Spain 28046
    129 Teva Investigational Site 3137 Murcia Spain 30120
    130 Teva Investigational Site 3138 Pontevedra Spain 36001
    131 Teva Investigational Site 3139 Santiago de Compostela Spain 15706
    132 Teva Investigational Site 3143 Valencia Spain 46010
    133 Teva Investigational Site 4204 Stockholm Sweden 14186
    134 Teva Investigational Site 4205 Stockholm Sweden 17176
    135 Teva Investigational Site 4206 Stockholm Sweden 18288
    136 Teva Investigational Site 8201 Izmir Turkey 35340
    137 Teva Investigational Site 5803 Dnipropetrovsk Ukraine 49027
    138 Teva Investigational Site 5802 Kyiv Ukraine 03110
    139 Teva Investigational Site 5804 Kyiv Ukraine 03115
    140 Teva Investigational Site 5800 Lviv Ukraine 79010
    141 Teva Investigational Site 5801 Vinnytsya Ukraine 21005
    142 Teva Investigational Site 3425 Liverpool United Kingdom L9 7LJ
    143 Teva Investigational Site 3424 London United Kingdom E1 2AT
    144 Teva Investigational Site 3422 Sheffield United Kingdom S10 2JF

    Sponsors and Collaborators

    • Teva Branded Pharmaceutical Products R&D, Inc.

    Investigators

    • Principal Investigator: Giancarlo Comi, U.O.Neurology-Neurorehabilitation and Clinical Neurophysiology

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT00509145
    Other Study ID Numbers:
    • MS-LAQ-301
    • EUDRACT 2007-003226-19
    First Posted:
    Jul 31, 2007
    Last Update Posted:
    Nov 2, 2021
    Last Verified:
    Sep 1, 2021
    Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.
    Relapsing
    Remitting
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Sclerosis

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 1106 participants were enrolled and randomized in the placebo-controlled (PC) double-blind period. Participants were randomized 1:1 to the treatment arms.
    Arm/Group Title Laquinimod Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    Period Title: Overall Study
    STARTED 550 556
    COMPLETED 437 427
    NOT COMPLETED 113 129

    Baseline Characteristics

    Arm/Group Title Laquinimod Placebo Total
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day Total of all reporting groups
    Overall Participants 550 556 1106
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.9
    (9.2)
    38.5
    (9.1)
    38.7
    (9.1)
    Sex: Female, Male (Count of Participants)
    Female
    391
    71.1%
    368
    66.2%
    759
    68.6%
    Male
    159
    28.9%
    188
    33.8%
    347
    31.4%
    Race/Ethnicity, Customized (Number) [Number]
    Race : Asian
    2
    0.4%
    1
    0.2%
    3
    0.3%
    Race : Black or African American
    1
    0.2%
    8
    1.4%
    9
    0.8%
    Race : White
    532
    96.7%
    532
    95.7%
    1064
    96.2%
    Race : Hispanic
    11
    2%
    9
    1.6%
    20
    1.8%
    Race : Other
    2
    0.4%
    4
    0.7%
    6
    0.5%

    Outcome Measures

    1. Primary Outcome
    Title Relapse Rate: Number of Confirmed Relapses During the Double Blind Study Period
    Description 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.
    Time Frame Up to Month 24

    Outcome Measure Data

    Analysis Population Description
    Intent to treat (ITT) analysis set included all randomized participants.
    Arm/Group Title Laquinimod Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    Measure Participants 550 556
    Mean (Standard Deviation) [Confirmed relapses]
    0.54
    (0.88)
    0.67
    (0.92)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laquinimod, Placebo
    Comments Response variable: number of relapses during 24 months. Offset based on the log of subject's exposure in years was employed to adjust for variability of treatment exposure. In addition to the treatment group, the Poisson regression model included the following covariates: baseline EDSS score, log of prior 2-year number of relapses+1 and Country or Geographical Region (CGR).
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0024
    Comments
    Method Over-dispersed Poisson Regression
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.770
    Confidence Interval (2-Sided) 95%
    0.650 to 0.911
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.066
    Estimation Comments Laquinimod 0.6 mg vs. placebo
    2. Secondary Outcome
    Title Composite Endpoint: Sum of the Number of T1 Gadolinium (Gd)-Enhanced Lesions on T1-Weighted MRI Images
    Description Composite score was calculated as the sum of the number of gadolinium (Gd)-enhanced lesions at Month 12 and the number of gadolinium (Gd)-enhanced lesions at Month 24 on T1-Weighted MRI scans.
    Time Frame Month 12, Month 24

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all randomized participants. Number of participants analyzed included the number of participants evaluable at each time point.
    Arm/Group Title Laquinimod Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    Measure Participants 482 464
    Mean (Standard Deviation) [Lesions]
    1.86
    (5.02)
    2.92
    (7.58)
    3. Secondary Outcome
    Title Composite Endpoint: Sum of the Number of New/Enlarging T2 Lesions
    Description Composite score calculated as the sum of T2 lesions at Months 12 and 24 that are new or enlarged.
    Time Frame Month 12, Month 24

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all randomized participants. Number of participants analyzed included the number of participants evaluable at each time point.
    Arm/Group Title Laquinimod Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    Measure Participants 482 464
    Mean (Standard Deviation) [Lesions]
    5.26
    (9.08)
    7.87
    (12.56)
    4. Secondary Outcome
    Title Accumulation of Physical Disability Measured by the Time to Confirmed Progression of Expanded Disability Status Scale (EDSS)
    Description EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). A confirmed progression of EDSS is defined as at least 1 point increase from baseline if baseline EDSS was between 0 and 5.0, or at least 0.5 point increase if baseline EDSS was 5.5 or higher, confirmed 3 months later. Participants were assessed between baseline and month 24 visit. Participants that met these criteria for any 3 consecutive months were counted in the progression category. Progression could not be confirmed during an MS relapse. Data is presented as a distribution of confirmed disease progression (CDP) events (number of participants with CDP).
    Time Frame Baseline to Month 24

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all randomized participants.
    Arm/Group Title Laquinimod Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    Measure Participants 550 556
    Progressed
    54
    9.8%
    78
    14%
    Progression Free
    496
    90.2%
    478
    86%
    5. Secondary Outcome
    Title Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score
    Description The Multiple Sclerosis Functional Composite is an instrument assessing disability that consists of 3 clinical assessments. The 3 are Timed 25-Foot Walk, 9-Hole Peg Test which measures upper extremity (arm and hand) function, and PASAT (Paced Auditory Serial Addition Test) which is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. A Z-score is used to define a common metric from the 3 assessments that constitute the MSFC score. The study's population at baseline was used as reference population for the Z-score calculation. A Z-score of 0 represents the population mean at baseline. Higher Z-scores correspond to an improved outcome.
    Time Frame Baseline, Month 24

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all randomized participants. Number of participants analyzed included the number of participants evaluable at each time point.
    Arm/Group Title Laquinimod Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    Measure Participants 424 420
    Mean (Standard Deviation) [Z score]
    0.0
    (0.4)
    0.0
    (0.7)

    Adverse Events

    Time Frame Baseline to 24 months
    Adverse Event Reporting Description Safety analysis included all participants that received at least one dose of study drug.
    Arm/Group Title Laquinimod 0.6 mg Placebo
    Arm/Group Description Laquinimod 0.6 mg capsule taken orally once a day Matching placebo capsule taken orally once a day
    All Cause Mortality
    Laquinimod 0.6 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/550 (0%) 3/556 (0.5%)
    Serious Adverse Events
    Laquinimod 0.6 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 61/550 (11.1%) 53/556 (9.5%)
    Blood and lymphatic system disorders
    Anaemia 1/550 (0.2%) 1 0/556 (0%) 0
    Lymphadenopathy 1/550 (0.2%) 1 0/556 (0%) 0
    Cardiac disorders
    Angina pectoris 1/550 (0.2%) 1 0/556 (0%) 0
    Myocardial infarction 0/550 (0%) 0 1/556 (0.2%) 1
    Myocardial ischaemia 1/550 (0.2%) 1 0/556 (0%) 0
    Arteriosclerosis coronary artery 1/550 (0.2%) 1 0/556 (0%) 0
    Eye disorders
    Uveitis 0/550 (0%) 0 1/556 (0.2%) 1
    Gastrointestinal disorders
    Abdominal hernia 1/550 (0.2%) 1 0/556 (0%) 0
    Abdominal pain 1/550 (0.2%) 2 1/556 (0.2%) 1
    Abdominal pain upper 0/550 (0%) 0 1/556 (0.2%) 1
    Diarrhoea 2/550 (0.4%) 2 0/556 (0%) 0
    Gastritis 1/550 (0.2%) 1 2/556 (0.4%) 2
    Gastrooesophageal reflux disease 1/550 (0.2%) 1 0/556 (0%) 0
    Vomiting 1/550 (0.2%) 4 0/556 (0%) 0
    Anal haemorrhage 0/550 (0%) 0 1/556 (0.2%) 1
    Ascites 1/550 (0.2%) 1 0/556 (0%) 0
    Duodenal ulcer perforation 1/550 (0.2%) 1 0/556 (0%) 0
    Gastroduodenitis 1/550 (0.2%) 1 0/556 (0%) 0
    Nausea 1/550 (0.2%) 1 0/556 (0%) 0
    Pancreatitis acute 1/550 (0.2%) 1 0/556 (0%) 0
    General disorders
    Chest discomfort 0/550 (0%) 0 1/556 (0.2%) 1
    Chest pain 1/550 (0.2%) 1 3/556 (0.5%) 4
    Pyrexia 2/550 (0.4%) 2 0/556 (0%) 0
    Drug interaction 0/550 (0%) 0 1/556 (0.2%) 1
    Nodule 0/550 (0%) 0 1/556 (0.2%) 1
    Oedema peripheral 2/550 (0.4%) 3 0/556 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 0/550 (0%) 0 1/556 (0.2%) 1
    Cholelithiasis 0/550 (0%) 0 2/556 (0.4%) 2
    Cholecystitis chronic 1/550 (0.2%) 1 0/556 (0%) 0
    Drug-induced liver injury 0/550 (0%) 0 1/556 (0.2%) 1
    Liver disorder 0/550 (0%) 0 1/556 (0.2%) 1
    Infections and infestations
    Appendicitis 5/550 (0.9%) 5 1/556 (0.2%) 1
    Cellulitis 2/550 (0.4%) 2 0/556 (0%) 0
    Nasopharyngitis 0/550 (0%) 0 1/556 (0.2%) 1
    Peritonitis 1/550 (0.2%) 1 0/556 (0%) 0
    Pneumonia 1/550 (0.2%) 1 2/556 (0.4%) 2
    Pyelonephritis 1/550 (0.2%) 1 1/556 (0.2%) 1
    Tonsillitis 1/550 (0.2%) 1 0/556 (0%) 0
    Vestibular neuronitis 1/550 (0.2%) 1 0/556 (0%) 0
    Infectious colitis 0/550 (0%) 0 1/556 (0.2%) 1
    Infectious mononucleosis 1/550 (0.2%) 1 0/556 (0%) 0
    Orchitis 1/550 (0.2%) 2 0/556 (0%) 0
    Staphylococcal pharyngitis 1/550 (0.2%) 1 0/556 (0%) 0
    Vaginitis bacterial 1/550 (0.2%) 1 0/556 (0%) 0
    Injury, poisoning and procedural complications
    Fall 1/550 (0.2%) 1 0/556 (0%) 0
    Lower limb fracture 1/550 (0.2%) 1 0/556 (0%) 0
    Meniscus injury 0/550 (0%) 0 1/556 (0.2%) 1
    Concussion 0/550 (0%) 0 1/556 (0.2%) 1
    Hand fracture 0/550 (0%) 0 1/556 (0.2%) 1
    Head injury 1/550 (0.2%) 1 0/556 (0%) 0
    Injury 0/550 (0%) 0 1/556 (0.2%) 1
    Joint injury 0/550 (0%) 0 1/556 (0.2%) 1
    Ligament rupture 0/550 (0%) 0 1/556 (0.2%) 1
    Spinal fracture 0/550 (0%) 0 1/556 (0.2%) 1
    Subdural haematoma 1/550 (0.2%) 1 0/556 (0%) 0
    Thoracic vertebral fracture 1/550 (0.2%) 1 0/556 (0%) 0
    Investigations
    Gamma-glutamyltransferase increased 1/550 (0.2%) 1 0/556 (0%) 0
    Alanine aminotransferase increased 1/550 (0.2%) 1 0/556 (0%) 0
    Aspartate aminotransferase increased 1/550 (0.2%) 1 0/556 (0%) 0
    Bacterial test positive 1/550 (0.2%) 1 0/556 (0%) 0
    Blood glucose increased 1/550 (0.2%) 1 0/556 (0%) 0
    Blood pressure increased 0/550 (0%) 0 1/556 (0.2%) 1
    Transaminases increased 1/550 (0.2%) 2 0/556 (0%) 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis 1/550 (0.2%) 1 0/556 (0%) 0
    Hypokalaemia 2/550 (0.4%) 4 0/556 (0%) 0
    Dehydration 1/550 (0.2%) 1 0/556 (0%) 0
    Folate deficiency 1/550 (0.2%) 1 0/556 (0%) 0
    Metabolic acidosis 1/550 (0.2%) 1 0/556 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/550 (0.2%) 2 0/556 (0%) 0
    Back pain 1/550 (0.2%) 1 0/556 (0%) 0
    Spondylolisthesis 0/550 (0%) 0 1/556 (0.2%) 1
    Musculoskeletal pain 0/550 (0%) 0 1/556 (0.2%) 1
    Spinal column stenosis 1/550 (0.2%) 1 0/556 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/550 (0.2%) 1 0/556 (0%) 0
    Intraductal proliferative breast lesion 0/550 (0%) 0 1/556 (0.2%) 1
    Invasive ductal breast carcinoma 1/550 (0.2%) 1 0/556 (0%) 0
    Ovarian adenoma 1/550 (0.2%) 1 0/556 (0%) 0
    Uterine leiomyoma 2/550 (0.4%) 2 1/556 (0.2%) 1
    Breast cancer metastatic 1/550 (0.2%) 1 0/556 (0%) 0
    Cholesteatoma 0/550 (0%) 0 1/556 (0.2%) 1
    Glioblastoma 1/550 (0.2%) 1 0/556 (0%) 0
    Lung neoplasm malignant 1/550 (0.2%) 1 0/556 (0%) 0
    Lymphoma 1/550 (0.2%) 1 0/556 (0%) 0
    Oesophageal adenocarcinoma 1/550 (0.2%) 1 0/556 (0%) 0
    Ovarian cancer 0/550 (0%) 0 1/556 (0.2%) 1
    Ovarian granulosa-theca cell tumour 0/550 (0%) 0 1/556 (0.2%) 1
    Prostate cancer 0/550 (0%) 0 1/556 (0.2%) 1
    Rectal cancer 0/550 (0%) 0 1/556 (0.2%) 1
    Nervous system disorders
    Cervicobrachial syndrome 1/550 (0.2%) 1 0/556 (0%) 0
    Epilepsy 1/550 (0.2%) 1 0/556 (0%) 0
    Headache 2/550 (0.4%) 2 0/556 (0%) 0
    Multiple sclerosis relapse 2/550 (0.4%) 2 5/556 (0.9%) 7
    Syncope 1/550 (0.2%) 1 0/556 (0%) 0
    Cognitive disorder 0/550 (0%) 0 1/556 (0.2%) 1
    Dyskinesia 1/550 (0.2%) 2 0/556 (0%) 0
    Encephalopathy 0/550 (0%) 0 1/556 (0.2%) 1
    Lumbosacral radiculopathy 0/550 (0%) 0 1/556 (0.2%) 1
    Migraine 1/550 (0.2%) 1 0/556 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Abortion threatened 1/550 (0.2%) 1 0/556 (0%) 0
    Psychiatric disorders
    Anxiety 1/550 (0.2%) 1 0/556 (0%) 0
    Completed suicide 0/550 (0%) 0 1/556 (0.2%) 1
    Depression 1/550 (0.2%) 2 1/556 (0.2%) 2
    Adjustment disorder 0/550 (0%) 0 1/556 (0.2%) 1
    Confusional state 0/550 (0%) 0 1/556 (0.2%) 1
    Delirium 1/550 (0.2%) 1 1/556 (0.2%) 1
    Delusion 0/550 (0%) 0 1/556 (0.2%) 1
    Hallucination, auditory 0/550 (0%) 0 1/556 (0.2%) 1
    Hallucination, visual 0/550 (0%) 0 1/556 (0.2%) 1
    Irritability 0/550 (0%) 0 1/556 (0.2%) 1
    Renal and urinary disorders
    Nephrolithiasis 1/550 (0.2%) 1 0/556 (0%) 0
    Urinary retention 1/550 (0.2%) 1 0/556 (0%) 0
    Renal colic 1/550 (0.2%) 1 0/556 (0%) 0
    Reproductive system and breast disorders
    Endometrial hyperplasia 0/550 (0%) 0 1/556 (0.2%) 1
    Endometriosis 0/550 (0%) 0 1/556 (0.2%) 1
    Menometrorrhagia 1/550 (0.2%) 1 0/556 (0%) 0
    Ovarian cyst 1/550 (0.2%) 1 1/556 (0.2%) 2
    Uterine polyp 1/550 (0.2%) 1 0/556 (0%) 0
    Uterine prolapse 1/550 (0.2%) 1 0/556 (0%) 0
    Breast haematoma 1/550 (0.2%) 1 0/556 (0%) 0
    Cervical cyst 0/550 (0%) 0 1/556 (0.2%) 1
    Cervical dysplasia 1/550 (0.2%) 1 0/556 (0%) 0
    Fallopian tube cyst 0/550 (0%) 0 1/556 (0.2%) 1
    Menorrhagia 0/550 (0%) 0 1/556 (0.2%) 1
    Ovarian adhesion 0/550 (0%) 0 1/556 (0.2%) 1
    Ovarian cyst ruptured 0/550 (0%) 0 1/556 (0.2%) 1
    Uterine cervical squamous metaplasia 0/550 (0%) 0 1/556 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/550 (0%) 0 2/556 (0.4%) 4
    Cough 1/550 (0.2%) 1 0/556 (0%) 0
    Pulmonary mass 0/550 (0%) 0 1/556 (0.2%) 1
    Respiratory disorder 1/550 (0.2%) 1 0/556 (0%) 0
    Surgical and medical procedures
    Cholecystectomy 0/550 (0%) 0 2/556 (0.4%) 2
    Hysterectomy 2/550 (0.4%) 2 4/556 (0.7%) 4
    Spinal fusion surgery 2/550 (0.4%) 3 0/556 (0%) 0
    Abortion induced 1/550 (0.2%) 1 1/556 (0.2%) 1
    Anorectal operation 0/550 (0%) 0 1/556 (0.2%) 1
    Appendicectomy 2/550 (0.4%) 2 0/556 (0%) 0
    Bone graft 1/550 (0.2%) 1 0/556 (0%) 0
    Bone operation 1/550 (0.2%) 1 0/556 (0%) 0
    Cholesteatoma removal 0/550 (0%) 0 1/556 (0.2%) 1
    Chondroplasty 1/550 (0.2%) 1 0/556 (0%) 0
    Cyst drainage 1/550 (0.2%) 1 0/556 (0%) 0
    Ligament operation 1/550 (0.2%) 1 0/556 (0%) 0
    Mastectomy 1/550 (0.2%) 1 0/556 (0%) 0
    Meniscus removal 1/550 (0.2%) 1 0/556 (0%) 0
    Plasmapheresis 0/550 (0%) 0 1/556 (0.2%) 1
    Rehabilitation therapy 1/550 (0.2%) 1 3/556 (0.5%) 3
    Renal stone removal 0/550 (0%) 0 1/556 (0.2%) 1
    Spinal decompression 1/550 (0.2%) 1 0/556 (0%) 0
    Spinal laminectomy 1/550 (0.2%) 1 0/556 (0%) 0
    Turbinectomy 0/550 (0%) 0 1/556 (0.2%) 1
    Uterine dilation and curettage 1/550 (0.2%) 1 0/556 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/550 (0.2%) 1 0/556 (0%) 0
    Arteriosclerosis 1/550 (0.2%) 1 0/556 (0%) 0
    Phlebitis superficial 1/550 (0.2%) 1 0/556 (0%) 0
    Thrombophlebitis superficial 1/550 (0.2%) 1 0/556 (0%) 0
    Vein disorder 1/550 (0.2%) 1 0/556 (0%) 0
    Other (Not Including Serious) Adverse Events
    Laquinimod 0.6 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 368/550 (66.9%) 346/556 (62.2%)
    Gastrointestinal disorders
    Abdominal pain upper 28/550 (5.1%) 33 29/556 (5.2%) 34
    Diarrhoea 42/550 (7.6%) 49 33/556 (5.9%) 41
    Nausea 34/550 (6.2%) 38 32/556 (5.8%) 38
    Abdominal pain 31/550 (5.6%) 36 15/556 (2.7%) 16
    General disorders
    Fatigue 25/550 (4.5%) 28 29/556 (5.2%) 36
    Pyrexia 20/550 (3.6%) 21 28/556 (5%) 34
    Infections and infestations
    Influenza 33/550 (6%) 39 44/556 (7.9%) 50
    Nasopharyngitis 100/550 (18.2%) 159 119/556 (21.4%) 199
    Sinusitis 29/550 (5.3%) 40 25/556 (4.5%) 38
    Upper respiratory tract infection 42/550 (7.6%) 61 48/556 (8.6%) 62
    Urinary tract infection 40/550 (7.3%) 60 24/556 (4.3%) 35
    Investigations
    Alanine aminotransferase increased 38/550 (6.9%) 49 15/556 (2.7%) 16
    Musculoskeletal and connective tissue disorders
    Arthralgia 47/550 (8.5%) 61 41/556 (7.4%) 51
    Back pain 89/550 (16.2%) 122 50/556 (9%) 73
    Pain in extremity 35/550 (6.4%) 47 38/556 (6.8%) 44
    Nervous system disorders
    Headache 123/550 (22.4%) 225 99/556 (17.8%) 176
    Dizziness 27/550 (4.9%) 29 29/556 (5.2%) 33
    Psychiatric disorders
    Depression 30/550 (5.5%) 31 32/556 (5.8%) 32
    Insomnia 36/550 (6.5%) 40 31/556 (5.6%) 39
    Respiratory, thoracic and mediastinal disorders
    Cough 40/550 (7.3%) 47 25/556 (4.5%) 29
    Oropharyngeal pain 23/550 (4.2%) 24 29/556 (5.2%) 34

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

    Results Point of Contact

    Name/Title Director, Clinical Research
    Organization Teva Branded Pharmaceutical Products R&D, Inc.
    Phone 1-888-483-8279
    Email USMedInfo@tevapharm.com
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT00509145
    Other Study ID Numbers:
    • MS-LAQ-301
    • EUDRACT 2007-003226-19
    First Posted:
    Jul 31, 2007
    Last Update Posted:
    Nov 2, 2021
    Last Verified:
    Sep 1, 2021