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NCT00509145: ALLEGRO

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

Completed Phase 3 Results posted Last updated 2 November 2021
What this trial tests

Phase 3 trial testing Laquinimod in Multiple Sclerosis in 1,106 participants. Completed in 8 November 2010.

Timeline
13 November 2007
Primary endpoint
8 November 2010
8 November 2010

Quick facts

Lead sponsorTeva Branded Pharmaceutical Products R&D, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment1,106
Start date13 November 2007
Primary completion8 November 2010
Estimated completion8 November 2010
Sites144 locations across Italy, Poland, Netherlands, Russia, Sweden, Estonia, Lithuania, Bulgaria

Drugs / interventions tested

Conditions studied

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

Adults 18 to 55, any sex, with Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Laquinimod0.54± 0.88
Placebo0.67± 0.92
Composite Endpoint: Sum of the Number of T1 Gadolinium (Gd)-Enhanced Lesions on T1-Weighted MRI Images Secondary · 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.

GroupValue95% CI
Laquinimod1.86± 5.02
Placebo2.92± 7.58
Composite Endpoint: Sum of the Number of New/Enlarging T2 Lesions Secondary · Month 12, Month 24

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

GroupValue95% CI
Laquinimod5.26± 9.08
Placebo7.87± 12.56
Accumulation of Physical Disability Measured by the Time to Confirmed Progression of Expanded Disability Status Scale (EDSS) Secondary · 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 p

GroupValue95% CI
Laquinimod54
Placebo78
Laquinimod496
Placebo478
Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score Secondary · 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 t

GroupValue95% CI
Laquinimod0.0± 0.4
Placebo0.0± 0.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to 24 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Laquinimod 0.6 mg
Serious: 61/550 (11%)
Deaths: 0/550
Placebo
Serious: 53/556 (10%)
Deaths: 3/556

Serious adverse events (156 terms)

ReactionSystemLaquinimod 0.6 mgPlacebo
AppendicitisInfections and infestations
Multiple sclerosis relapseNervous system disorders
HysterectomySurgical and medical procedures
Chest painGeneral disorders
Rehabilitation therapySurgical and medical procedures
DiarrhoeaGastrointestinal disorders
GastritisGastrointestinal disorders
PyrexiaGeneral disorders
CholelithiasisHepatobiliary disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HeadacheNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
CholecystectomySurgical and medical procedures
Spinal fusion surgerySurgical and medical procedures
Oedema peripheralGeneral disorders
AppendicectomySurgical and medical procedures
AnaemiaBlood and lymphatic system disorders
Angina pectorisCardiac disorders
Myocardial infarctionCardiac disorders
Myocardial ischaemiaCardiac disorders
UveitisEye disorders
Abdominal herniaGastrointestinal disorders
Other adverse events (21 terms — click to expand)

ReactionSystemLaquinimod 0.6 mgPlacebo
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
InfluenzaInfections and infestations
DiarrhoeaGastrointestinal disorders
Urinary tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Alanine aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
NauseaGastrointestinal disorders
DepressionPsychiatric disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
FatigueGeneral disorders
SinusitisInfections and infestations
DizzinessNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders

Most-reported serious reactions: Appendicitis, Multiple sclerosis relapse, Hysterectomy, Chest pain, Rehabilitation therapy, Diarrhoea, Gastritis, Pyrexia.

Data from ClinicalTrials.gov NCT00509145 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Placebo-controlled trial of oral laquinimod for multiple sclerosis.
    Comi G, Jeffery D, Kappos L, Montalban X, et al · · 2012 · cited 272× · PMID 22417253 · DOI 10.1056/nejmoa1104318
  2. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage.
    Filippi M, Rocca MA, Pagani E, De Stefano N, et al · · 2014 · cited 87× · PMID 24029546 · DOI 10.1136/jnnp-2013-306132
  3. Current and Possible Future Therapeutic Options for Huntington's Disease.
    Ferguson MW, Kennedy CJ, Palpagama TH, Waldvogel HJ, et al · · 2022 · cited 66× · PMID 35615642 · DOI 10.1177/11795735221092517
  4. Disability Outcome Measures in Phase III Clinical Trials in Multiple Sclerosis.
    Uitdehaag BMJ. · · 2018 · cited 43× · PMID 29926371 · DOI 10.1007/s40263-018-0530-8
  5. Laquinimod in the treatment of multiple sclerosis: a review of the data so far.
    Thöne J, Linker RA. · · 2016 · cited 41× · PMID 27042003 · DOI 10.2147/dddt.s55308
  6. New approaches in the management of multiple sclerosis.
    Barten LJ, Allington DR, Procacci KA, Rivey MP. · · 2010 · cited 41× · PMID 21151622 · DOI 10.2147/dddt.s9331
  7. Monoclonal antibody therapy in multiple sclerosis: Paradigm shifts and emerging challenges.
    Fontoura P. · · 2010 · cited 20× · PMID 21124072 · DOI 10.4161/mabs.2.6.13270
  8. Laquinimod Safety Profile: Pooled Analyses from the ALLEGRO and BRAVO Trials.
    Sørensen PS, Comi G, Vollmer TL, Montalban X, et al · · 2017 · cited 17× · PMID 28243182 · DOI 10.7224/1537-2073.2015-024

Verify or expand the search:

Other trials of Laquinimod

Trials testing the same drug.

Other recruiting trials for Multiple Sclerosis

Currently open trials in the same condition.

Other Teva Branded Pharmaceutical Products R&D, Inc. trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing