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CompletedNCT02284568ARPEGGIOUpdated Mar 10, 2022Results posted

A Phase 2 Clinical Study in Subjects With Primary Progressive Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of Two Oral Doses of Laquinimod Either of 0.6 mg/Day or 1.5mg/Day (Experimental Drug) as Compared to Placebo

A Phase 2 interventional study of Placebo and Laquinimod in Primary Progressive Multiple Sclerosis, sponsored by Teva Branded Pharmaceutical Products R&D, Inc.. Completed at 99 sites in 10 countries. Open to participants aged 25 Years to 55 Years. Per ClinicalTrials.gov, last updated 2022-03-10.

Sponsored by Teva Branded Pharmaceutical Products R&D, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
374
Allocation
Randomized
Ages
25 Years to 55 Years
Sex
All
01

Study summary

This Phase 2 study is intended to serve as a proof of concept for potential treatment with laquinimod in patients with PPMS. The study is also aimed at evaluating 2 doses of laquinimod in this population.

Read the detailed description

Due to serious cardiovascular adverse events, Data Monitoring Committee (DMC) made a recommendation to stop all laquinimod treatment arms above 0.6 mg in the multiple sclerosis (MS) trials; therefore the 1.5 mg treatment arm in the ARPEGGIO study was discontinued as of 01 January 2016.

The DMC did not identify any definite cardiovascular risk in the 0.6 mg treatment arm, but felt that long term monitoring for emergence of any potential signal was necessary. Therefore, the 0.6 mg treatment arm was continued while the sponsor closely monitored cardiovascular events in all laquinimod studies. Prior to 01 January 2016, eligible patients were randomized in a 1:1:1 ratio into 1 of the following treatment arms (a total of 286 patients were randomized 1:1:1 prior to

01 January 2016):

  • Laquinimod 0.6 mg daily
  • Laquinimod 1.5 mg daily
  • Daily placebo

As of 01 January 2016, following the decision to discontinue the laquinimod 1.5 mg dose arm, additional eligible patients (87 patients) who were enrolled were randomized in a 1:1 ratio into one of the following treatment arms:

  • Laquinimod 0.6 mg daily
  • Daily placebo
02

Conditions studied

  • Primary Progressive Multiple Sclerosis

Keywords

  • multiple sclerosis
  • primary progressive multiple sclerosis
  • oral immunomodulator
03

In context

Multiple Sclerosis

3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.

This study's enrollment of 374 is above the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.

Browse Multiple Sclerosis studies →

Lead sponsor

Teva Branded Pharmaceutical Products R&D, Inc. is the lead sponsor of 205 studies on the registry; none are open to participants now.

Of its 49 completed or terminated interventional studies of FDA-regulated products, 47 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
25 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patients must have a confirmed and documented PPMS diagnosis as defined by the 2010 Revised McDonald criteria
  2. Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in either or both brain and spinal cord
  3. Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5, inclusive, at both screening and baseline visits
  4. Documented evidence of clinical disability progression in the 2 years prior to screening.
  5. Functional System Score (FSS) of > or equal 2 for the pyramidal system or gait impairment due to lower extremity dysfunction
  6. Patients must be between 25 to 55 years of age, inclusive
  7. Women of child-bearing potential must practice an acceptable method of birth control for 30 days before taking the study drug, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment is administered.
  8. Patients must sign and date a written informed consent prior to entering the study.
  9. Patients must be willing and able to comply with the protocol requirements for the duration of the study.

Exclusion criteria

Exclusion Criteria:

  1. Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis.
  2. Progressive neurological disorder other than PPMS.
  3. Any MRI record showing presence of cervical cord compression.
  4. Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms.
  5. Relevant history of vitamin B12 deficiency.
  6. Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.
  7. Use of experimental or investigational drugs in a clinical study within 24 weeks prior to baseline. Use of a currently marketed drug in a clinical study within 24 weeks prior to baseline would not be exclusionary, provided no other exclusion criteria are met.
  8. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine within 48 weeks prior to baseline.
  9. Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate (TECFIDERA®, Biogen Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-β (either 1a or 1b), intravenous immunoglobulin, or plasmapheresis within 8 weeks prior to baseline.
  10. Use of teriflunomide (AUBAGIO®, Sanofi) within 2 years prior to baseline, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to baseline.

  11. Prior use of monoclonal antibodies ever, except for:

    1. natalizumab (TYSABRI®, Biogen Idec Inc), if given more than 24 weeks prior to baseline AND the patient is John Cunningham (JC) virus antibody test negative (as per medical history)
    2. rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than 80 cells/μL
  12. Use of mitoxantrone (NOVANTRONE®, Immunex) within 5 years prior to screening. Use of mitoxantrone >5 years before screening is allowed in patients with normal ejection fraction and who did not exceed the total lifetime maximal dose.
  13. Previous use of laquinimod.
  14. Chronic (eg, more than 30 consecutive days or monthly dosing, with the intent of MS disease modification) systemic (intravenous, intramuscular or oral) corticosteroid treatment within 8 weeks prior to baseline.
  15. Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi).
  16. Previous total body irradiation or total lymphoid irradiation.
  17. Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of any kind.
  18. Patients who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) within 12 weeks prior to baseline.
  19. Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to baseline.
  20. Use of inducers of CYP3A4 within 2 weeks prior to baseline.
  21. Pregnancy or breastfeeding.
  22. Serum levels ≥3× upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at screening.
  23. Serum direct bilirubin which is ≥2×ULN at screening.
  24. Patients with a clinically significant or unstable medical or surgical condition that (in the opinion of the Investigator) would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests or chest X-ray.
  25. A known history of hypersensitivity to gadolinium (Gd).
  26. Glomerular filtration rate (GFR) \< or equal 60 mL/min at screening visit.
  27. Inability to successfully undergo MRI scanning, including claustrophobia.
  28. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
374 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    once daily oral dose

    Drug: Placebo

  • Experimental
    Laquinimod 0.6 mg

    1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.

    Drug: Laquinimod · Drug: Placebo

  • Experimental
    Laquinimod 1.5 mg

    3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.

    Drug: Laquinimod

Interventions

  • DrugPlacebo

    Placebo

  • DrugLaquinimod

    Laquinimod capsules in 0.5 mg and 0.6 mg strengths

    Also known as: TV-5600

  • DrugPlacebo

    Placebo capsules

06

What researchers measure

Primary outcomes

  1. Percent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model

    Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. BA was analyzed using baseline-adjusted repeated measures analysis of covariance (ANCOVA- SAS® PROC MIXED) in which 1 contrast was constructed in order to compare between laquinimod 0.6 mg and placebo. The statistical model was a repeated measures analysis of covariance with treatment group, week, treatment group by week interaction, normalized brain volume at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects. Only on-treatment observations (include all the assessments done up to one month after the last dose of the study drug) were included. Values are adjusted means. The cancelled laquinimod 1.5 mg treatment arm was not included in the repeated measures ANCOVA model analysis. However PBVC by visit data are offered in outcome #2.

    Time frame: Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48 and including early termination visits

  2. Percent Brain Volume Change (PBVC) From Baseline to Weeks 24 and 48

    Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. Early termination scans of participants who discontinued the study after week 36 are considered scans at week 48.

    Time frame: Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48

Secondary outcomes

  1. Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 48

    CDP was defined as increase in EDSS of \>=1 point from baseline EDSS, if EDSS at entry is ≤5.0 or increase of \>=0.5 point, if EDSS at entry is \>=5.5. This increase should be confirmed after at least 12 weeks. Progression cannot be confirmed during a protocol defined relapse. EDSS is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS scale ranges from 0 to 10 in 0.5 unit increments with 0=no disability and 10=death due to MS. Only an Examining Neurologist administered the EDSS. The Examining Neurologist did not have access to the patient's medical records or source documents, including previous EDSS forms or adverse events. If a patient died due to MS disease progression, the patient was analyzed as having CDP with the time to CDP as the onset date of progression. If a patient died due to MS before having progression, then the time to disability progression was censored using the date of death.

    Time frame: Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)

  2. Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) or the Timed 25-foot Walk (T25FW) Test up to Week 48

    CDP was defined as increase in EDSS of \>=1 point from baseline EDSS, if EDSS at entry is ≤5.0 or increase of \>=0.5 point, if EDSS at entry is \>=5.5 confirmed after at least 12 weeks, OR increase of \>= 20% from baseline in the T25FW test, confirmed after at least 12 weeks. EDSS quantifies disability in MS and monitors changes in the level of disability over time. The EDSS scale is 0-10 in 0.5 unit increments with 0=no disability and 10=death due to MS. The T25-FW is a quantitative mobility and leg function performance test based on the average time of two trials in which participants walk 25 feet as quickly as possible. Increasing time scores indicate increasing impairment. If a patient died due to MS disease progression, the patient was analyzed as having CDP with the time to CDP as the onset date of progression. If a patient died due to MS before having progression, then the time to disability progression was censored using the date of death.

    Time frame: Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)

  3. Change From Baseline for the Timed 25-foot Walk (T25FW) Score at Weeks 12, 24, 36 and 48

    The T25FW is a quantitative mobility and leg function performance test based on the average time of two trials in which participants walk 25 feet as quickly as possible. In cases when a patient could not complete a T25FW trial due to the physical limitations, a value of 180 seconds was assigned for that trial (this is the maximal possible value for the T25FW test). Increasing time scores indicate increasing impairment. Baseline values are summaries of observed values. Week values are change from baseline values.

    Time frame: Baseline (Week 0), Weeks 12, 24, 36, 48

  4. Number of New T2 Brain Lesions at Week 48

    Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new T2 lesions at week 48 as compared to baseline. Scans of patients who discontinued the study after week 36 are considered scans at week 48, and are included in week 48.

    Time frame: Baseline (Week 0), 48 weeks

  5. Participants With Treatment-Emergent Adverse Events (TEAEs)

    An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

    Time frame: Day 1 up to Week 130 (longest duration of treatment)

07

Results

Posted Nov 2, 2018

Participant flow

Participant flow — Overall Study
MilestonePlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Started14013995
Safety population14013895
Completed week 48 mri - on treatment1131070
Completed109930
Not completed314695
Withdrew: Adverse event294
Withdrew: Withdrawal by subject22211
Withdrew: Noncompliance with study drug admin120
Withdrew: Noncompliance100
Withdrew: Protocol violation010
Withdrew: Sponsor requested patient stop treatment0090
Withdrew: Lost to follow-up030
Withdrew: Lack of efficacy470
Withdrew: Other120
Withdrew: Withdrew before taking study drug010

Outcome measures

PrimaryPercent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model

Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. BA was analyzed using baseline-adjusted repeated measures analysis of covariance (ANCOVA- SAS® PROC MIXED) in which 1 contrast was constructed in order to compare between laquinimod 0.6 mg and placebo. The statistical model was a repeated measures analysis of covariance with treatment group, week, treatment group by week interaction, normalized brain volume at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects. Only on-treatment observations (include all the assessments done up to one month after the last dose of the study drug) were included. Values are adjusted means. The cancelled laquinimod 1.5 mg treatment arm was not included in the repeated measures ANCOVA model analysis. However PBVC by visit data are offered in outcome #2.

Time frame:
Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48 and including early termination visits
Reported as:
Mean · percentage change from baseline
Percent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model
percentage change from baselinePlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Percent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model-0.454 ± 0.0897-0.438 ± 0.0945—
Statistical analysis
  • Placebo vs Laquinimod 0.6 mg · Repeated Measures ANCOVA · p = 0.903 (significance at 0.05.) · Mean difference (final values): 0.016 · 95% CI -0.2390 to 0.2705
PrimaryPercent Brain Volume Change (PBVC) From Baseline to Weeks 24 and 48

Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. Early termination scans of participants who discontinued the study after week 36 are considered scans at week 48.

Time frame:
Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48
Reported as:
Mean · percentage change from baseline
Percent Brain Volume Change (PBVC) From Baseline to Weeks 24 and 48
percentage change from baselinePlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Week 24-0.241 ± 0.8978-0.042 ± 0.7537-0.820 ± 1.2693
Week 48-0.455 ± 0.9770-0.418 ± 0.98060.550
SecondaryPercentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 48

CDP was defined as increase in EDSS of \>=1 point from baseline EDSS, if EDSS at entry is ≤5.0 or increase of \>=0.5 point, if EDSS at entry is \>=5.5. This increase should be confirmed after at least 12 weeks. Progression cannot be confirmed during a protocol defined relapse. EDSS is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS scale ranges from 0 to 10 in 0.5 unit increments with 0=no disability and 10=death due to MS. Only an Examining Neurologist administered the EDSS. The Examining Neurologist did not have access to the patient's medical records or source documents, including previous EDSS forms or adverse events. If a patient died due to MS disease progression, the patient was analyzed as having CDP with the time to CDP as the onset date of progression. If a patient died due to MS before having progression, then the time to disability progression was censored using the date of death.

Time frame:
Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)
Reported as:
Number · percentage of participants
Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 48
percentage of participantsPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 4823171
Statistical analysis
  • Placebo vs Laquinimod 0.6 mg · Log Rank · p = 0.426 (significance at 0.05. p-value was from a log-rank test, and estimate and confidence limits were from a Cox model with treatment group as fixed effect, due to the violation of the proportionality assumption.) · Hazard ratio (hr): 0.8 · 95% CI 0.48 to 1.37Laquinimod 0.6 mg vs placebo
SecondaryPercentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) or the Timed 25-foot Walk (T25FW) Test up to Week 48

CDP was defined as increase in EDSS of \>=1 point from baseline EDSS, if EDSS at entry is ≤5.0 or increase of \>=0.5 point, if EDSS at entry is \>=5.5 confirmed after at least 12 weeks, OR increase of \>= 20% from baseline in the T25FW test, confirmed after at least 12 weeks. EDSS quantifies disability in MS and monitors changes in the level of disability over time. The EDSS scale is 0-10 in 0.5 unit increments with 0=no disability and 10=death due to MS. The T25-FW is a quantitative mobility and leg function performance test based on the average time of two trials in which participants walk 25 feet as quickly as possible. Increasing time scores indicate increasing impairment. If a patient died due to MS disease progression, the patient was analyzed as having CDP with the time to CDP as the onset date of progression. If a patient died due to MS before having progression, then the time to disability progression was censored using the date of death.

Time frame:
Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)
Reported as:
Number · percentage of participants
Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) or the Timed 25-foot Walk (T25FW) Test up to Week 48
percentage of participantsPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) or the Timed 25-foot Walk (T25FW) Test up to Week 4834322
Statistical analysis
  • Placebo vs Laquinimod 0.6 mg · Regression, Cox · p = 0.867 (significance at 0.05.) · Hazard ratio (hr): 1.0 · 95% CI 0.68 to 1.59Laquinimod 0.6 mg vs placebo
SecondaryChange From Baseline for the Timed 25-foot Walk (T25FW) Score at Weeks 12, 24, 36 and 48

The T25FW is a quantitative mobility and leg function performance test based on the average time of two trials in which participants walk 25 feet as quickly as possible. In cases when a patient could not complete a T25FW trial due to the physical limitations, a value of 180 seconds was assigned for that trial (this is the maximal possible value for the T25FW test). Increasing time scores indicate increasing impairment. Baseline values are summaries of observed values. Week values are change from baseline values.

Time frame:
Baseline (Week 0), Weeks 12, 24, 36, 48
Reported as:
Median · seconds
Change From Baseline for the Timed 25-foot Walk (T25FW) Score at Weeks 12, 24, 36 and 48
secondsPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Baseline7.750 (3.15 to 46.00)7.600 (4.20 to 88.40)6.850 (4.25 to 62.00)
Week 120.100 (-8.85 to 16.00)0.050 (-56.90 to 113.05)0.100 (-6.15 to 172.00)
Week 240.100 (-20.50 to 16.85)0.350 (-58.50 to 113.05)0.150 (-4.00 to 172.15)
Week 360.200 (-18.15 to 21.80)0.450 (-64.60 to 113.05)12.550 (1.65 to 27.60)
Week 480.300 (-22.65 to 134.00)0.050 (-63.50 to 68.35)—
Statistical analysis
  • Placebo vs Laquinimod 0.6 mg · Repeated Measures ANCOVA · p = 0.248 (significance at 0.05. The p-value for ranked change from baseline values was from a repeated measures analysis of covariance with trt group, week, treatment group by week interaction, rank of T25FW score at baseline, and country as fixed effects.) · Mean difference (final values): -0.325 · 95% CI -0.8500 to 0.2000Laquinimod 0.6 mg vs. placebo treatment effect
SecondaryNumber of New T2 Brain Lesions at Week 48

Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new T2 lesions at week 48 as compared to baseline. Scans of patients who discontinued the study after week 36 are considered scans at week 48, and are included in week 48.

Time frame:
Baseline (Week 0), 48 weeks
Reported as:
Mean · lesions
Number of New T2 Brain Lesions at Week 48
lesionsPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Number of New T2 Brain Lesions at Week 483.5 ± 10.821.3 ± 3.011.0
Statistical analysis
  • Placebo vs Laquinimod 0.6 mg · negative binomial regression model · p = 0.001 (significance at 0.05) · Risk ratio (rr): 0.4 · 95% CI 0.26 to 0.69Laquinimod 0.6 mg vs. placebo risk ratio
SecondaryParticipants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Time frame:
Day 1 up to Week 130 (longest duration of treatment)
Reported as:
Count of participants · Participants
Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Any TEAE10911563
Severe TEAE663
Treatment-related TEAE274129
Deaths001
Serious TEAE6103
Withdrawn from treatment due to TEAE284

Adverse events

Collected over Day 1 up to Week 130 (longest duration of treatment). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/140 (0%)6/140 (4.3%)77/140 (55%)
Laquinimod 0.6 mg0/138 (0%)10/138 (7.2%)74/138 (53.6%)
Laquinimod 1.5 mg1/95 (1.1%)3/95 (3.2%)40/95 (42.1%)
Most frequent serious events
Showing 10 of 23
Most frequent serious events
EventPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
Urinary tract infectionInfections and infestations2/1401/1380/95
Angina unstableCardiac disorders0/1400/1381/95
Testicular abscessInfections and infestations0/1400/1381/95
Lumbosacral plexopathyNervous system disorders0/1400/1381/95
Neuromyelitis optica spectrum disorderNervous system disorders0/1400/1381/95
Oedema peripheralGeneral disorders0/1401/1380/95
Bacterial pyelonephritisInfections and infestations0/1401/1380/95
PneumoniaInfections and infestations0/1401/1380/95
UrosepsisInfections and infestations0/1401/1380/95
Radius fractureInjury, poisoning and procedural complications0/1401/1380/95
Most frequent other events
Showing 10 of 14
Most frequent other events
EventPlaceboLaquinimod 0.6 mgLaquinimod 1.5 mg
NasopharyngitisInfections and infestations24/14024/1384/95
HeadacheNervous system disorders16/14014/13815/95
Back painMusculoskeletal and connective tissue disorders15/14012/1385/95
InfluenzaInfections and infestations13/1407/1382/95
Upper respiratory tract infectionInfections and infestations6/14012/1382/95
Urinary tract infectionInfections and infestations11/1409/1384/95
DiarrhoeaGastrointestinal disorders6/1409/1381/95
FallInjury, poisoning and procedural complications9/1409/1384/95
NauseaGastrointestinal disorders3/1404/1386/95
ArthralgiaMusculoskeletal and connective tissue disorders6/1408/1386/95

Baseline characteristics

Intent to treat population

Age, Continuous
Age, Continuous(years)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Mean46.6 ± 7.1846.1 ± 6.6846.1 ± 7.2146.3 ± 6.99
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Female675745169
Male738250205
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
White13813292362
Black0224
Asian0202
Other2316
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Not HIspanic or Latino13513491360
Hispanic or Latino45110
Unknown1034
Weight
Weight(kg)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Mean73.97 ± 16.80975.91 ± 16.66873.47 ± 14.83174.57 ± 16.275
Height
Height(cm)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Mean171.25 ± 9.818172.61 ± 9.246171.03 ± 9.677171.70 ± 9.573
Body Mass Index
Body Mass Index(kg/m^2)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Mean25.136 ± 5.028325.373 ± 4.553925.026 ± 4.100225.196 ± 4.6208
Time Since First MS Symptom
Time Since First MS Symptom(years)PlaceboLaquinimod 0.6 mgLaquinimod 1.5 mgTotal
Mean7.4 ± 5.228.3 ± 6.338.5 ± 5.618.0 ± 5.76

3 further baseline measures are reported on the registry.

08

Study locations

99 sites
  • Teva Investigational Site 12966
    Phoenix, Arizona 85018, United States
  • Teva Investigational Site 12967
    Newport Beach, California 92663, United States
  • Teva Investigational Site 12962
    San Francisco, California 94158, United States
  • Teva Investigational Site 12964
    Aurora, Colorado 80045, United States
  • Teva Investigational Site 12973
    Northbrook, Illinois 60062, United States
  • Teva Investigational Site 12975
    Kansas City, Kansas 66160-7314, United States
  • Teva Investigational Site 12969
    Lenexa, Kansas 66214, United States
  • Teva Investigational Site 12977
    Golden Valley, Minnesota 55422, United States
  • Teva Investigational Site 13010
    Golden Valley, Minnesota 55422, United States
  • Teva Investigational Site 12965
    Chesterfield, Missouri 63017, United States
  • Teva Investigational Site 12968
    Saint Louis, Missouri 63110, United States
  • Teva Investigational Site 12963
    New York, New York 10016, United States
  • Teva Investigational Site 12971
    Charlotte, North Carolina 28207, United States
  • Teva Investigational Site 12976
    Columbus, Ohio 43221, United States
  • Teva Investigational Site 12970
    Uniontown, Ohio 44685, United States
  • Teva Investigational Site 11089
    Calgary, AL T2N 4Z1, Canada
  • Teva Investigational Site 11084
    Halifax, Nova Scotia B3H 4K4, Canada
  • Teva Investigational Site 11081
    Ottawa, Ontario K1H 8L6, Canada
  • Teva Investigational Site 11087
    Toronto, Ontario M5B-1W8, Canada
  • Teva Investigational Site 11082
    Montreal, Quebec H3A 2B4, Canada
  • Teva Investigational Site 11088
    Quebec, G1J 1Z4, Canada
  • Teva Investigational Site 32505
    Bad Mergentheim, 97980, Germany
  • Teva Investigational Site 32512
    Bamberg, 96049, Germany
  • Teva Investigational Site 32510
    Berlin, 10117, Germany
  • Teva Investigational Site 32522
    Bochum, 44791, Germany
  • Teva Investigational Site 32509
    Dresden, 01307, Germany
  • Teva Investigational Site 32517
    Dusseldorf, 40225, Germany
  • Teva Investigational Site 32543
    Goettigen, 37075, Germany
  • Teva Investigational Site 32514
    Hamburg, 20099, Germany
  • Teva Investigational Site 32507
    Hannover, 30625, Germany
  • Teva Investigational Site 32513
    Munchen, 81675, Germany
  • Teva Investigational Site 32504
    Munchen, D-81377, Germany
  • Teva Investigational Site 32516
    Rostock, 18057, Germany
  • Teva Investigational Site 32523
    Trier, 54292, Germany
  • Teva Investigational Site 32503
    Ulm, 89081, Germany
  • Teva Investigational Site 32511
    Wurzburg, 97080, Germany
  • Teva Investigational Site 30106
    Cefalu, 90015, Italy
  • Teva Investigational Site 30110
    Firenze, 50134, Italy
  • Teva Investigational Site 30105
    Gallarate, 21013, Italy
  • Teva Investigational Site 30108
    Genova, 16132, Italy
  • Teva Investigational Site 30102
    Milano, 20127, Italy
  • Teva Investigational Site 30107
    Orbassano, 10043, Italy
  • Teva Investigational Site 30103
    Padova, 35128, Italy
  • Teva Investigational Site 30101
    Rome, 00133, Italy
  • Teva Investigational Site 30104
    Rome, ?00152, Italy
  • Teva Investigational Site 38068
    Amsterdam, 1081 HV, Netherlands
  • Teva Investigational Site 38067
    Nijmegen, 6532 SZ, Netherlands
  • Teva Investigational Site 38069
    Sittard, 6162 BG, Netherlands
  • Teva Investigational Site 53262
    Bialystok, 15-402, Poland
  • Teva Investigational Site 53250
    Bydgoszcz, 85-795, Poland
  • Teva Investigational Site 53253
    Gdansk, 80-803, Poland
  • Teva Investigational Site 53257
    Katowice, 40-635, Poland
  • Teva Investigational Site 53258
    Katowice, 40-684, Poland
  • Teva Investigational Site 53256
    Katowice, 40-749, Poland
  • Teva Investigational Site 53255
    Kielce, 25-726, Poland
  • Teva Investigational Site 53260
    Lublin, 20-954, Poland
  • Teva Investigational Site 53261
    Olsztyn, 10-560, Poland
  • Teva Investigational Site 53252
    Warsaw, 02-957, Poland
  • Teva Investigational Site 50285
    Kaluga, 248007, Russian Federation
  • Teva Investigational Site 50288
    Kazan, 420021, Russian Federation
  • Teva Investigational Site 50290
    Kazan, 420103, Russian Federation
  • Teva Investigational Site 50294
    Kirov, 610006, Russian Federation
  • Teva Investigational Site 50292
    Krasnoyarsk, 660022, Russian Federation
  • Teva Investigational Site 50287
    Moscow, 127018, Russian Federation
  • Teva Investigational Site 50291
    Nizhny Novgorod, 603126, Russian Federation
  • Teva Investigational Site 50286
    Novosibirsk, 630007, Russian Federation
  • Teva Investigational Site 50295
    Perm, 614990, Russian Federation
  • Teva Investigational Site 50293
    Saint Petersburg, 197022, Russian Federation
  • Teva Investigational Site 50289
    St. Petersburg, 194044, Russian Federation
  • Teva Investigational Site 31108
    Barcelona, 08036, Spain
  • Teva Investigational Site 31106
    Barcelona, 8035, Spain
  • Teva Investigational Site 31105
    El Palmar, 30120, Spain
  • Teva Investigational Site 31111
    Lleida, 25198, Spain
  • Teva Investigational Site 31112
    Madrid, 28040, Spain
  • Teva Investigational Site 31192
    Madrid, 28223, Spain
  • Teva Investigational Site 31101
    Malaga, 29010, Spain
  • Teva Investigational Site 31104
    San Sebastian, 20014, Spain
  • Teva Investigational Site 31102
    Sevilla, 41009, Spain
  • Teva Investigational Site 31100
    Valencia, 46026, Spain
  • Teva Investigational Site 58158
    Dnipropetrovsk, 49005, Ukraine
  • Teva Investigational Site 58159
    Ivano-Frankivsk, 76014, Ukraine
  • Teva Investigational Site 58157
    Kharkiv, 61068, Ukraine
  • Teva Investigational Site 58160
    Kyiv, ?03110, Ukraine
  • Teva Investigational Site 58152
    Lutsk, 43005, Ukraine
  • Teva Investigational Site 58154
    Lviv, 79010, Ukraine
  • Teva Investigational Site 58153
    Lviv, 79044, Ukraine
  • Teva Investigational Site 58156
    Zaporizhzhia, 69068, Ukraine
  • Teva Investigational Site 58150
    Zaporizhzhya, 69035, Ukraine
  • Teva Investigational Site 58151
    Zaporizhzhya, 69600, Ukraine
  • Teva Investigational Site 34190
    Bristol, BS10 5NB, United Kingdom
  • Teva Investigational Site 34188
    Edinburgh, EH4 2XU, United Kingdom
  • Teva Investigational Site 34189
    Exeter, EX2 5DW, United Kingdom
  • Teva Investigational Site 34182
    Liverpool, L9 7LJ, United Kingdom
  • Teva Investigational Site 34181
    London, E1 2AT, United Kingdom
  • Teva Investigational Site 34183
    Nottingham, NG7 2UH, United Kingdom
  • Teva Investigational Site 34184
    Oxford, OX3 9DU, United Kingdom
  • Teva Investigational Site 34186
    Plymouth, PL6 8DH, United Kingdom
  • Teva Investigational Site 34185
    Stoke-on-Trent, ST4 6GQ, United Kingdom
  • Teva Investigational Site 34187
    Swansea, SA6 6NL, United Kingdom
09

References and documents

Publications

  • Giovannoni G, Knappertz V, Steinerman JR, Tansy AP, Li T, Krieger S, Uccelli A, Uitdehaag BMJ, Montalban X, Hartung HP, Pia Sormani M, Cree BAC, Lublin F, Barkhof F. A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis. Neurology. 2020 Aug 25;95(8):e1027-e1040. doi: 10.1212/WNL.0000000000010284. Epub 2020 Jul 10. PubMed 32651286 ↗

Study documents

  • Study protocol · Feb 1, 2016
  • Statistical analysis plan · Jun 1, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 10, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02284568
Lead sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Responsible party
Sponsor
First posted
Nov 6, 2014
Start date
Jan 12, 2015
Primary completion
May 4, 2017
Completion
Oct 1, 2017
Results posted
Nov 2, 2018
Last update
Mar 10, 2022

Study contacts

Teva Medical Expert, MD
study director · Teva Branded Pharmaceutical Products R&D, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

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Discussion

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