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An Extension Study of LAQ/5062 Exploring the Long Term Safety, Tolerability and Clinical Effect Parameters During the Disease

Phase 2
Terminated
Conditions
Relapsing Remitting Multiple Sclerosis
Interventions
Drug: Placebo
Registration Number
NCT00745615
Lead Sponsor
Teva Pharmaceutical Industries, Ltd.
Brief Summary

This is a multinational, multicenter, randomized, double-blind, parallel-group active extension of LAQ/5062 study (NCT00349193), assessing the tolerability, safety and efficacy of two doses (0.3 mg and 0.6 mg) of laquinimod, orally administered in participants with relapsing remitting multiple sclerosis (RRMS), followed by an open-label phase of laquinimod 0.6 mg daily. This study is LAQ/5063 (i.e., double-blind extension) and LAQ/5063 OL (i.e., subsequent open-label extension). - The first period of the extension study is an active, double-blind period. Participants from the active treatment arms in LAQ/5062 continue their assigned treatment in blinded fashion. Participants who were assigned to placebo treatment in LAQ/5062 are equally randomized in blinded-fashion to laquinimod 0.6 mg or laquinimod 0.3 mg. - Once termination visit of LAQ/5063 active double-blind phase (completion of the full 36 weeks or as requested by the Sponsor) is performed, all participants continue on laquinimod 0.6 mg daily as an open-label intervention. The open-label period continues as long as the Sponsor continues the development of laquinimod 0.6 mg for RRMS or early discontinuation.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
257
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Double-Blind: Placebo/Laquinimod 0.3 mgPlaceboParticipants who will be receiving placebo matching to laquinimod 0.3 mg tablet once daily orally in double-blind core study, will receive laquinimod 0.3 mg tablet once daily orally in double-blind extension period of this study for up to Week 36.
Double-Blind: Placebo/Laquinimod 0.6 mgPlaceboParticipants who will be receiving placebo matching to laquinimod 0.6 mg (2 tablets of placebo) once daily orally in double-blind core study, will receive laquinimod 0.6 mg once daily orally in double-blind extension period of this study for up to Week 36.
Double-Blind: Placebo/Laquinimod 0.3 mgLaquinimodParticipants who will be receiving placebo matching to laquinimod 0.3 mg tablet once daily orally in double-blind core study, will receive laquinimod 0.3 mg tablet once daily orally in double-blind extension period of this study for up to Week 36.
Double-Blind: Laquinimod 0.6 mgLaquinimodParticipants who will be receiving laquinimod 0.6 mg (2 tablets of 0.3 mg each) once daily orally in double-blind core study, will continue to receive laquinimod 0.6 mg once daily orally in double-blind extension period of this study for up to Week 36.
Double-Blind: Laquinimod 0.3 mgLaquinimodParticipants who will be receiving laquinimod 0.3 milligram (mg) tablet once daily orally in double-blind core study, will continue to receive laquinimod 0.3 mg tablet once daily orally in double-blind extension period of this study for up to Week 36.
Open Label: Laquinimod 0.6 mgLaquinimodParticipants who will be receiving laquinimod 0.6 mg (2 tablets of 0.3 mg each) once daily orally either in double-blind core study or double-blind extension period, will receive laquinimod 0.6 mg capsule once daily orally in open-label extension period of this study until termination (as long as the Sponsor will continue the development of laquinimod 0.6 mg for RRMS) or early discontinuation (up to approximately 10.5 years).
Double-Blind: Placebo/Laquinimod 0.6 mgLaquinimodParticipants who will be receiving placebo matching to laquinimod 0.6 mg (2 tablets of placebo) once daily orally in double-blind core study, will receive laquinimod 0.6 mg once daily orally in double-blind extension period of this study for up to Week 36.
Open-Label: Laquinimod 0.3 mg/Laquinimod 0.6 mgLaquinimodParticipants who will be receiving laquinimod 0.3 mg tablet once daily orally either in double-blind core study or double-blind extension period, will receive laquinimod 0.6 mg capsule once daily orally in open-label extension period of this study until termination (as long as the Sponsor will continue the development of laquinimod 0.6 mg for RRMS) or early discontinuation (up to approximately 10.5 years).
Primary Outcome Measures
NameTimeMethod
Double-Blind Extension Period: Number of Participants With Adverse Events (AEs)Baseline (Week 0) to Week 36

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Open-label Extension Period: Number of Participants With AEsBaseline (Month 0/termination visit of double-blind extension phase [completion of full 36 weeks] until termination (as long as the Sponsor continued the development of laquinimod 0.6 mg for RRMS) or early discontinuation (up to approximately 10.5 years)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Double-Blind Period: Number of Participants Who Prematurely Discontinued From the Study Due to Any Reason and Due to AEsBaseline (Week 0) to Week 36

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.

Open-Label Period: Number of Participants Who Prematurely Discontinued From the Study Due to Any Reason and Due to AEsBaseline (Month 0/termination visit of double-blind extension phase [completion of full 36 weeks] until termination (as long as the Sponsor continued the development of laquinimod 0.6 mg for RRMS) or early discontinuation (up to approximately 10.5 years)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.

Secondary Outcome Measures
NameTimeMethod
Double-Blind Period: Number of New T2 LesionsAt the end of active double-blind phase or termination/early termination visit (up to Week 36)

Inflammatory disease activity was assessed by MRI measurement of the number of new T2 lesions.

Double-Blind Period: Kurtzke's Expanded Disability Status Scale (EDSS) ScoreAt the end of active double-blind phase or termination/early termination visit (up to Week 36)

EDSS (developed by John F. Kurtzke) is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and other functions). Each functional system score and an overall score ranges from 0 to 10, where 0 = Normal; 1-1.5 = No disability, but some abnormal neurological signs; 2-2.5 = Minimal disability; 3-4.5 = Moderate disability, affecting daily activities, but can still walk; 5-8 = More severe disability, impairing daily activities and requiring assistance with walking; 8.5-9.5 = Very severe disability, restricting to bed; 10 = Death due to MS. A lower score indicated less disability.

Double-Blind Period: Volume of T2 LesionsAt the end of active double-blind phase or termination/early termination visit (up to Week 36)

Volume of T2 lesion was assessed by magnetic MRI.

Double-Blind Period: Number of Enhancing Lesions on T1-Weighted ImagesAt the end of active double-blind phase or termination/early termination visit (up to Week 36)

Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions. T1-weighted scan was taken after administration of gadolinium-gadopentetic acid (Gd-DTPA).

Double-Blind Period: Relapse Rate: Total Number of Confirmed RelapsesBaseline (Week 0) up to end of active double-blind phase or termination/early termination visit (up to Week 36)

Relapse was defined as the appearance of one or more new neurological abnormalities or the reappearance of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in the absence of fever or any infection) and immediately preceded by an improving neurological state of at least 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 an increase of at least 0.5 in the Expanded disability status scale (EDSS); or one grade in the score of 2 or more of the 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in the score of one of the FS as compared to the previous evaluation. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]).

Double-Blind Period: Percentage of Relapse-Free ParticipantsBaseline (Week 0) up to end of active double-blind phase or termination/early termination visit (up to Week 36)

Relapse was defined as the appearance of one or more new neurological abnormalities or the reappearance of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in the absence of fever or any infection) and immediately preceded by an improving neurological state of at least 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 an increase of at least 0.5 in the EDSS; or one grade in the score of 2 or more of the 7 FS (excluding changes in bowel or bladder function or cognition); or 2 grades in the score of one of the FS as compared to the previous evaluation. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS).

Double-Blind Period: Number of New Hypointense T1 Lesion on Enhanced T1 ScansAt the end of active double-blind phase or termination/early termination visit (up to Week 36)

Inflammatory disease activity was assessed by MRI measurement of the number of new hypointense T1 lesions.

Trial Locations

Locations (45)

Teva Investigational Site 382

🇨🇿

Hradec Kralove 3, Czechia

Teva Investigational Site 380

🇨🇿

Praha 2, Czechia

Teva Investigational Site 384

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Praha 5- Motol, Czechia

Teva Investigational Site 681

🇩🇪

Berlin, Germany

Teva Investigational Site 684

🇩🇪

Erfurt, Germany

Teva Investigational Site 687

🇩🇪

Hamburg, Germany

Teva Investigational Site 683

🇩🇪

Mainz, Germany

Teva Investigational Site 686

🇩🇪

Ulm, Germany

Teva Investigational Site 685

🇩🇪

Wuerzburg, Germany

Teva Investigational Site 580

🇭🇺

Debrecen, Hungary

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Teva Investigational Site 382
🇨🇿Hradec Kralove 3, Czechia

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