The Efficacy, Safety, and Tolerability of Laquinimod in Participants With Relapsing Remitting Multiple Sclerosis (RRMS)

Browse trials for

• Multiple Sclerosis 3,452
• Multiple Sclerosis, Relapsing-Remitting 602
• Sclerosis 3,139

Study arms

• Placebo comparator
  Placebo-Controlled Phase: Placebo

  Participants will receive 2 capsules of placebo (matching to laquinimod 0.6 milligrams \[mg\]) once daily orally for up to 24 months.

  Drug: Placebo

• Experimental
  Placebo-Controlled Phase: Laquinimod 0.6 mg

  Participants will receive 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months.

  Drug: Laquinimod · Drug: Placebo

• Experimental
  Placebo-Controlled Phase: Laquinimod 1.2 mg

  Participants will receive laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.

  Drug: Laquinimod

• Experimental
  Active Treatment Phase: Laquinimod 0.6 mg

  Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, will receive 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months.

  Drug: Laquinimod · Drug: Placebo

• Experimental
  Active Treatment Phase: Laquinimod 1.2 mg

  Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, will receive laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.

  Drug: Laquinimod

• No intervention
  Active Treatment Phase: Off Drug

  Participants who were discontinued from treatment with laquinimod 1.2 mg during the placebo-controlled phase due to sponsor decision after 01 January 2016 will continue the active-treatment phase off drug for 24 months.

Interventions

• DrugLaquinimod

  Laquinimod will be administered as per the dose and schedule specified in the respective arms.

• DrugPlacebo

  Placebo matching to laquinimod will be administered as per the schedule specified in the respective arms.

Primary outcomes

1. Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months)

   Time to CDP was defined as the time to a sustained increase in Kurtzke's Expanded Disability Status Scale (EDSS) score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least three months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]). Data is presented as distribution of CDP (number of participants with CDP) sustained for 3 months.

   Time frame: Baseline to Month 24

Secondary outcomes

1. Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15

   Brain atrophy was defined by the percent change in brain volume from baseline to Month 15. For participants who prematurely discontinued treatment or completed the placebo-controlled phase before Month 15, the last available measurement was used, provided it was performed at least 9 months following the initiation of study drug.

   Time frame: Baseline, Month 15

2. Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse)

   Relapse was defined as appearance of one or more new neurological abnormalities or reappearance or worsening of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in 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 EDSS; or one grade in score of 2 or more of 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in score of one of the FS as compared to previous evaluation. EDSS assesses disability in 8 FS with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of relapsing participants (number of participants with confirmed relapse).

   Time frame: Baseline to Month 24

3. Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months)

   Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 6 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 6 months.

   Time frame: Baseline to Month 24

4. Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months)

   Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 9 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 9 months.

   Time frame: Baseline to Month 24

Other outcomes

1. Placebo-Controlled Phase: 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.

   Time frame: Baseline up to Month 24

2. Active-Treatment Phase: 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. 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.

   Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

3. Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities

   Clinically significant vital signs abnormalities included: Pulse rate: greater than or equal to (\>=) 120 beats per minute (bpm) and increase from baseline of \>=30 bpm, \<=45 bpm and decrease from baseline of \>=30 bpm; Systolic blood pressure: \>=180 millimeters of mercury (mmHg) and increase from baseline of \>=30 mmHg, \<=90 and decrease from baseline of \>=30 mmHg; Diastolic blood pressure: \>=100 mmHg and increase from baseline of \>=20 mmHg, \<=50 mmHg and decrease from baseline of \>=20 mmHg.

   Time frame: Baseline up to Week 24

4. Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities

   Clinically significant vital signs abnormalities included: Pulse rate: \>=120 bpm and increase from baseline of \>=30 bpm, \<=45 bpm and decrease from baseline of \>=30 bpm; Systolic blood pressure: \>=180 mmHg and increase from baseline of \>=30 mmHg, \<=90 and decrease from baseline of \>=30 mmHg; Diastolic blood pressure: \>=100 mmHg and increase from baseline of \>=20 mmHg, \<=50 mmHg and decrease from baseline of \>=20 mmHg.

   Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

5. Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters

   ECG parameters included: PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.

   Time frame: Baseline, Endpoint (Month 24)

6. Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters

   ECG parameters included: PR interval, QRS interval, QTcF and QTcB. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.

   Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase), endpoint (Month 24 of active-treatment phase)

7. Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry

   Potentially clinically significant serum chemistry abnormalities included: Glucose \<=3 and \>=13.88 millimoles per liter (mmol/L); Alanine aminotransferase (ALT) (in units per liter \[U/L\]), aspartate aminotransferase (AST) (in U/L), alkaline phosphatase (in U/L), gamma-glutamyltransferase (GGT) (in U/L), creatine phosphokinase (CPK) (in U/L), C-reactive protein (CRP) (in milligrams per liter \[mg/L\]), pancreatic amylase (in U/L)\>=3 \* upper limit of normal (ULN); Fibrinogen \>=6 grams per liter (gm/L); Sodium \<=130 and \>=150 mmol/L; Potassium \<=3.2 and \>=5.5 mmol/L; Calcium \<=1.87 and \>=2.75 mmol/L; Phosphate \<=0.65 and \>=1.61 mmol/L.

   Time frame: Baseline up to Month 24

8. Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry

   Potentially clinically significant serum chemistry abnormalities included: Glucose \<=3 and \>=13.88 mmol/L; ALT (in U/L), AST (in U/L), alkaline phosphatase (in U/L), GGT (in U/L), CPK (in U/L), CRP (in mg/L), pancreatic amylase (in U/L)\>=3 \* ULN; Fibrinogen \>=6 gm/L; Sodium \<=130 and \>=150 mmol/L; Potassium \<=3.2 and \>=5.5 mmol/L; Calcium \<=1.87 and \>=2.75 mmol/L; Phosphate \<=0.65 and \>=1.61 mmol/L; Blood urea nitrogen (in mmol/L); Total bilirubin \>=28 micromols per liter (micromols/L); Creatinine \>=117 micromols/L; Albumin \<=25 gm/L.

   Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

9. Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values

   Potentially clinically significant hematological abnormalities included: Hemoglobin \<=11.5 grams per deciliter (gm/dL) in males and \<=10 gm/dL in females; White blood cells (WBCs) count \<=2.5 and \>=21\*10\^9 per liter (L); Absolute neutrophil count (ANC) \<=1.49\*10\^9 per L; Platelet count \<=100 and \>=600\*10\^9 per L.

   Time frame: Baseline up to Month 24

10. Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values

    Potentially clinically significant hematological abnormalities included: Hemoglobin \<=11.5, \>=20 gm/dL in males, and \<=10, \>=18.5 gm/dL in females; WBCs count \<=2.5 and \>=21\*10\^9 per L; ANC \<=1.49\*10\^9 per L; Platelet count \<=100 and \>=600\*10\^9 per L.

    Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

Baseline characteristics

Publications

• Comi G, Dadon Y, Sasson N, Steinerman JR, Knappertz V, Vollmer TL, Boyko A, Vermersch P, Ziemssen T, Montalban X, Lublin FD, Rocca MA, Volkinshtein R, Rubinchick S, Halevy N, Filippi M. CONCERTO: A randomized, placebo-controlled trial of oral laquinimod in relapsing-remitting multiple sclerosis. Mult Scler. 2022 Apr;28(4):608-619. doi: 10.1177/13524585211032803. Epub 2021 Aug 11. PubMed 34378456 ↗