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

Relapsing Remitting Multiple Sclerosis Clinical Trial

Official title:

An Active Extension of LAQ/5062 Study. A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Safety, Tolerability and Efficacy of Two Doses (0.3 mg and 0.6 mg) of Laquinimod, Orally Administered in Relapsing Remitting (R-R) Multiple Sclerosis (MS) Subjects (Study LAQ/5063 Active Double-Blind Phase) Followed by an Open Label Phase of Laquinimod 0.6 mg Daily (LAQ/5063 OL)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00745615
• Other study ID #: LAQ/5063OL
• Secondary ID: LAQ/50632005-004
• Status: Terminated
• Phase: Phase 2
• Start date: December 7, 2005
• Est. completion date: July 23, 2017

Study information

• Verified date: March 2019
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 257
• Est. completion date: July 23, 2017
• Est. primary completion date: July 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria - Participants must have completed the 36 weeks of treatment (completion of the full 36 weeks or as requested by the Sponsor) of the active double-blind phase. - Women of childbearing potential (for example, women who were not postmenopausal or surgically sterilized) must have practiced 2 acceptable methods of birth control for the duration of the study and until 30 days after the last dose of study medication (acceptable methods of birth control in this open-label extension phase included intrauterine devices, barrier methods [condom or diaphragm with spermicide], and hormonal methods of birth control [for example, oral contraceptive, contraceptive patch, and long-acting injectable contraceptive]). - Participants must have been willing and able to comply with the protocol requirements for the duration of LAQ/5063 OL. - Participants must have given signed, written informed consent prior to entering LAQ/5063 OL. - For the 36 months further extension: Participants must have completed the 24 months of treatment of the first period of the open label phase. Exclusion Criteria - For the 36 month further extension: Premature discontinuation from LAQ/5063 OL phase prior to completion of 24 months of treatment period. - Pregnancy or breastfeeding. - Participants with clinically significant or unstable medical or surgical condition, detected or worsened during the active double-blind phase of LAQ/5063, which would have precluded safe and complete study participation. - Use of experimental drugs, immunosuppressive drugs, and/or participation in clinical studies within the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Previous treatment with immunomodulators with the exception of laquinimod (including interferon [IFN] 1a and 1b, glatiramer acetate, and intravenous [IV] immunoglobulin) within 2 months prior to entering the open-label phase for those subjects who had a time gap between termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of corticosteroids within 30 days prior to entering the open-label phase, except for IV methylprednisolone 1 grams/day for a maximum of 3 days, in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of potent inhibitors of cytochrome P3A4 (CYP3A4) within 2 weeks prior to LAQ/5063 OL and/or use of fluoxetine 1 month prior to entering LAQ/5063 OL, in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of the following substrates of cytochrome P1A2 (CYP1A2): theophylline and/or warfarin within 2 weeks prior to entering LAQ/5063 OL, in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of amiodarone in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Following the switch to new formulation (capsules), hypersensitivity to mannitol, meglumine, or sodium stearyl fumarate.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Laquinimod
Laquinimod tablets/capsules will be administered as per the dose and schedule specified in the respective arms.
• Placebo
Placebo matching to laquinimod will be administered as per the dose and schedule specified in the respective arms.

Locations

Country	Name	City	State
Czechia	Teva Investigational Site 382	Hradec Kralove 3
Czechia	Teva Investigational Site 380	Praha 2
Czechia	Teva Investigational Site 384	Praha 5- Motol
Germany	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
Hungary	Teva Investigational Site 580	Debrecen
Hungary	Teva Investigational Site 581	Gyula
Hungary	Teva Investigational Site 583	Miskolc
Hungary	Teva Investigational Site 584	Veszprem
Israel	Teva Investigational Site 982	Haifa
Israel	Teva Investigational Site 980	Jerusalem
Israel	Teva Investigational Site 981	Ramat -Gan	IL
Italy	Teva Investigational Site 483	Cagliari
Italy	Teva Investigational Site 484	Milano
Italy	Teva Investigational Site 486	Milano
Italy	Teva Investigational Site 488	Siena
Poland	Teva Investigational Site 281	Bydgoszcz
Poland	Teva Investigational Site 280	Katowice
Poland	Teva Investigational Site 285	Katowice
Poland	Teva Investigational Site 283	Lodz
Poland	Teva Investigational Site 284	Lublin
Poland	Teva Investigational Site 282	Wroclaw
Russian Federation	Teva Investigational Site 186	Moscow
Russian Federation	Teva Investigational Site 187	Moscow
Russian Federation	Teva Investigational Site 188	Moscow
Russian Federation	Teva Investigational Site 189	Moscow
Russian Federation	Teva Investigational Site 180	Saint Petersburg
Russian Federation	Teva Investigational Site 181	St. Petersburg
Russian Federation	Teva Investigational Site 182	St. Petersburg
Russian Federation	Teva Investigational Site 184	St. Petersburg
Russian Federation	Teva Investigational Site 185	St. Petersburg
Spain	Teva Investigational Site 782	Barakaldo
Spain	Teva Investigational Site 785	Barcelona
Spain	Teva Investigational Site 781	Bilbao
Spain	Teva Investigational Site 784	L'Hospitalet de Llobregat
Spain	Teva Investigational Site 780	Madrid
Spain	Teva Investigational Site 783	Sevilla
United Kingdom	Teva Investigational Site 884	Liverpool
United Kingdom	Teva Investigational Site 882	London
United Kingdom	Teva Investigational Site 881	Sheffield
United Kingdom	Teva Investigational Site 883	Stoke on Trent

Sponsors (1)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries, Ltd.

Countries where clinical trial is conducted

Czechia,  Germany,  Hungary,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Double-Blind Extension Period: Number of Participants With Adverse Events (AEs)	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'.	Baseline (Week 0) to Week 36
Primary	Open-label Extension Period: Number of Participants With AEs	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'.	Baseline (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)
Primary	Double-Blind Period: Number of Participants Who Prematurely Discontinued From the Study Due to Any Reason and Due to AEs	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.	Baseline (Week 0) to Week 36
Primary	Open-Label Period: Number of Participants Who Prematurely Discontinued From the Study Due to Any Reason and Due to AEs	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.	Baseline (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)
Secondary	Double-Blind Period: Relapse Rate: Total Number of Confirmed Relapses	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]).	Baseline (Week 0) up to end of active double-blind phase or termination/early termination visit (up to Week 36)
Secondary	Double-Blind Period: Percentage of Relapse-Free Participants	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).	Baseline (Week 0) up to end of active double-blind phase or termination/early termination visit (up to Week 36)
Secondary	Double-Blind Period: Number of Enhancing Lesions on T1-Weighted Images	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).	At the end of active double-blind phase or termination/early termination visit (up to Week 36)
Secondary	Double-Blind Period: Number of New T2 Lesions	Inflammatory disease activity was assessed by MRI measurement of the number of new T2 lesions.	At the end of active double-blind phase or termination/early termination visit (up to Week 36)
Secondary	Double-Blind Period: Volume of T2 Lesions	Volume of T2 lesion was assessed by magnetic MRI.	At the end of active double-blind phase or termination/early termination visit (up to Week 36)
Secondary	Double-Blind Period: Number of New Hypointense T1 Lesion on Enhanced T1 Scans	Inflammatory disease activity was assessed by MRI measurement of the number of new hypointense T1 lesions.	At the end of active double-blind phase or termination/early termination visit (up to Week 36)
Secondary	Double-Blind Period: Kurtzke's Expanded Disability Status Scale (EDSS) Score	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.	At the end of active double-blind phase or termination/early termination visit (up to Week 36)