Trial Outcomes & Findings for A Clinical Study in Participants With Huntington's Disease (HD) to Assess Efficacy and Safety of Three Oral Doses of Laquinimod (NCT NCT02215616)

Last Updated: 2020-05-04

Results Overview

UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and Total Functional Capacity (TFC) score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

352 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2020-05-04

Participant Flow

A total of 468 participants were screened, of whom 116 participants were screen failures and 352 participants were enrolled. Of 352 enrolled participants, 123 participants were randomized in 1:1:1:1 ratio to receive laquinimod 0.5, 1.0, 1.5 milligrams/day (mg/day), or matching placebo prior to 10 January 2016.

As of 10 January 2016; following recommendation of Data Safety Monitoring Board (DSMB), treatment of laquinimod 1.5 mg dose arm was discontinued as a proactive safety measure. After 10 January 2016; additional eligible participants, who were enrolled, were randomized in 1:1:1 ratio to receive laquinimod 0.5 mg/day, 1.0 mg/day, or matching placebo.

Participant milestones

Participant milestones
Measure	Placebo Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.
Overall Study STARTED	108	107	107	30
Overall Study Received at Least 1 Dose of Study Drug	108	107	106	29
Overall Study COMPLETED	97	90	93	17
Overall Study NOT COMPLETED	11	17	14	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.
Overall Study Sponsor requested to stop study drug	0	0	1	4
Overall Study Death	1	0	0	0
Overall Study Adverse Event	7	4	9	2
Overall Study Withdrawal by Subject	1	8	2	5
Overall Study Non-compliance	0	2	1	0
Overall Study Protocol Violation	0	2	0	0
Overall Study Lost to Follow-up	1	1	0	1
Overall Study Other than specified	1	0	1	1

Baseline Characteristics

'Number analyzed' signifies participants evaluable for this parameter.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=108 Participants Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg n=107 Participants Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg n=107 Participants Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg n=30 Participants Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.	Total n=352 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 7.76 • n=108 Participants	43.3 years STANDARD_DEVIATION 7.75 • n=107 Participants	44.0 years STANDARD_DEVIATION 7.83 • n=107 Participants	45.5 years STANDARD_DEVIATION 6.03 • n=30 Participants	43.9 years STANDARD_DEVIATION 7.64 • n=352 Participants
Sex: Female, Male Female	56 Participants n=108 Participants	52 Participants n=107 Participants	54 Participants n=107 Participants	11 Participants n=30 Participants	173 Participants n=352 Participants
Sex: Female, Male Male	52 Participants n=108 Participants	55 Participants n=107 Participants	53 Participants n=107 Participants	19 Participants n=30 Participants	179 Participants n=352 Participants
Race/Ethnicity, Customized White	104 Participants n=108 Participants	103 Participants n=107 Participants	105 Participants n=107 Participants	28 Participants n=30 Participants	340 Participants n=352 Participants
Race/Ethnicity, Customized Black	0 Participants n=108 Participants	1 Participants n=107 Participants	1 Participants n=107 Participants	0 Participants n=30 Participants	2 Participants n=352 Participants
Race/Ethnicity, Customized Asian	2 Participants n=108 Participants	0 Participants n=107 Participants	0 Participants n=107 Participants	1 Participants n=30 Participants	3 Participants n=352 Participants
Race/Ethnicity, Customized Other	0 Participants n=108 Participants	1 Participants n=107 Participants	0 Participants n=107 Participants	0 Participants n=30 Participants	1 Participants n=352 Participants
Race/Ethnicity, Customized Missing	2 Participants n=108 Participants	2 Participants n=107 Participants	1 Participants n=107 Participants	1 Participants n=30 Participants	6 Participants n=352 Participants
Unified Huntington's Disease Rating Scale - Total Motor Score (UHDRS-TMS)	26.4 units on a scale STANDARD_DEVIATION 14.63 • n=108 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	24.0 units on a scale STANDARD_DEVIATION 13.23 • n=107 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	22.1 units on a scale STANDARD_DEVIATION 10.74 • n=106 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	26.8 units on a scale STANDARD_DEVIATION 13.75 • n=30 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	24.4 units on a scale STANDARD_DEVIATION 13.12 • n=351 Participants • 'Number analyzed' signifies participants evaluable for this parameter.
Normalized Caudate Volume	6.06 milliliters (mL) STANDARD_DEVIATION 1.857 • n=106 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	5.78 milliliters (mL) STANDARD_DEVIATION 1.818 • n=103 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	6.02 milliliters (mL) STANDARD_DEVIATION 1.781 • n=102 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	5.39 milliliters (mL) STANDARD_DEVIATION 1.218 • n=28 Participants • 'Number analyzed' signifies participants evaluable for this parameter.	5.90 milliliters (mL) STANDARD_DEVIATION 1.781 • n=339 Participants • 'Number analyzed' signifies participants evaluable for this parameter.

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis set (FAS) included all participants in the ITT population (all randomized participants) who received at least 1 dose of study drug and had at least 1 post-baseline TMS assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=98 Participants Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg n=92 Participants Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg n=95 Participants Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg n=4 Participants Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.
Change From Baseline in UHDRS-TMS at Week 52	1.3 units on a scale Standard Deviation 8.00	1.4 units on a scale Standard Deviation 8.34	2.0 units on a scale Standard Deviation 7.27	11.0 units on a scale Standard Deviation 7.12

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: FAS included all participants in the ITT population (all randomized participants) who received at least 1 dose of study drug and had at least 1 post-baseline TMS assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Brain atrophy was assessed using magnetic resonance imaging (MRI) measures of caudate volume. Caudate volume atrophy is a sensitive biomarker in very early HD and correlates with disease progression. Brain atrophy in the caudate refers to the shrinkage in volume, so that a decrease in volume is a positive value, while an increase in volume is a negative value. Percent change in caudate volume at Week 52 was calculated as the change in caudate volume since the baseline visit, divided by the baseline caudate volume and multiplied by 100.

Outcome measures

Outcome measures
Measure	Placebo n=87 Participants Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg n=87 Participants Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg n=85 Participants Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg n=2 Participants Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.
Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52	5.13 percent change Standard Deviation 3.265	4.03 percent change Standard Deviation 3.275	3.14 percent change Standard Deviation 3.360	4.11 percent change Standard Deviation 0.598

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 62 other events

Deaths: 1 deaths

Laquinimod 0.5 mg

Serious events: 7 serious events

Other events: 69 other events

Deaths: 0 deaths

Laquinimod 1.0 mg

Serious events: 5 serious events

Other events: 58 other events

Deaths: 0 deaths

Laquinimod 1.5 mg

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=108 participants at risk Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg n=107 participants at risk Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg n=106 participants at risk Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg n=29 participants at risk Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.
Cardiac disorders Defect conduction intraventricular	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Burn infection	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Gastrointestinal viral infection	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Osteomyelitis chronic	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femur fracture	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Multiple injuries	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Road traffic accident	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Traumatic liver injury	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Nervous system disorders Cluster headache	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Product Issues Device dislocation	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Depression	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Psychiatric decompensation	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Psychotic disorder	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Suicide attempt	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Mediastinal haematoma	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Cutaneous lupus erythematosus	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.

Measure	Placebo n=108 participants at risk Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.	Laquinimod 0.5 mg n=107 participants at risk Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.0 mg n=106 participants at risk Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.	Laquinimod 1.5 mg n=29 participants at risk Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.
Gastrointestinal disorders Abdominal pain	0.93% 1/108 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.5% 7/107 • Number of events 10 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/106 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	2.8% 3/108 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/107 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/106 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	8.3% 9/108 • Number of events 9 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	11.2% 12/107 • Number of events 14 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	8.5% 9/106 • Number of events 11 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	10.3% 3/29 • Number of events 6 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	3.7% 4/108 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	4.7% 5/107 • Number of events 10 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	4.7% 5/106 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	13.8% 4/29 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	2.8% 3/108 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.5% 7/107 • Number of events 10 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.8% 4/106 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Influenza	6.5% 7/108 • Number of events 9 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	7.5% 8/107 • Number of events 8 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.6% 7/106 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	17.6% 19/108 • Number of events 33 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	9.3% 10/107 • Number of events 12 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	9.4% 10/106 • Number of events 13 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	6.5% 7/108 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/107 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/106 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	4.6% 5/108 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/106 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	5.6% 6/108 • Number of events 8 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	8.3% 9/108 • Number of events 15 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	9.3% 10/107 • Number of events 12 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	4.7% 5/106 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 6 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ligament sprain	1.9% 2/108 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/107 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.8% 4/106 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Investigations Amylase increased	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	7.5% 8/107 • Number of events 10 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	5.7% 6/106 • Number of events 10 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Investigations Blood folate decreased	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	5.7% 6/106 • Number of events 6 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Investigations Haemoglobin decreased	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/106 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	10.3% 3/29 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Investigations Pancreatic enzymes increased	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/107 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/106 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	4.6% 5/108 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	4.7% 5/107 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.8% 4/106 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	6.5% 7/108 • Number of events 8 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.5% 7/107 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	7.5% 8/106 • Number of events 12 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Nervous system disorders Balance disorder	0.00% 0/108 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.93% 1/107 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Nervous system disorders Chorea	2.8% 3/108 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/107 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/106 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Nervous system disorders Headache	6.5% 7/108 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	17.8% 19/107 • Number of events 22 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	13.2% 14/106 • Number of events 31 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	17.2% 5/29 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Anxiety	3.7% 4/108 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/107 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.94% 1/106 • Number of events 1 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Depression	4.6% 5/108 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/107 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/106 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Insomnia	3.7% 4/108 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.7% 4/107 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	1.9% 2/106 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	6.9% 2/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Psychiatric disorders Irritability	3.7% 4/108 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	5.6% 6/107 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/106 • Number of events 3 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	3.4% 1/29 • Number of events 2 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	3.7% 4/108 • Number of events 5 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	2.8% 3/107 • Number of events 4 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	5.7% 6/106 • Number of events 7 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.	0.00% 0/29 • Baseline up to Week 56 Safety analysis set included all participants who had received at least 1 dose of study drug.