Trial Outcomes & Findings for Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH) (NCT NCT01617655)

Results Overview

Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

107 participants

Primary outcome timeframe

From Baseline to Week 52

Results posted on

2016-10-04

Participant Flow

The study was conducted at 33 centers in 5 countries. A total of 206 participants were screened between June 2012 and May 2013, 99 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.

Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, and intensity of statin treatment. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo:alirocumab) after confirmation of selection criteria. 107 participants were randomized.

Participant milestones

Participant milestones
Measure	Placebo Q2W Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.	Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Overall Study STARTED	35	72
Overall Study Treated	35	72
Overall Study COMPLETED	26	43
Overall Study NOT COMPLETED	9	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Q2W Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.	Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Overall Study Adverse Event	2	3
Overall Study Poor compliance to protocol	1	4
Overall Study Participants moved	0	4
Overall Study Consent withdrawn by participant	1	1
Overall Study Last visit outside protocol visit window	1	10
Overall Study Site closure	3	5
Overall Study Other than specified above	1	2

Baseline Characteristics

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=72 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.	Total n=107 Participants Total of all reporting groups
Age, Continuous	52.1 years STANDARD_DEVIATION 11.2 • n=5 Participants	49.8 years STANDARD_DEVIATION 14.2 • n=7 Participants	50.6 years STANDARD_DEVIATION 13.3 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	37 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	35 Participants n=7 Participants	57 Participants n=5 Participants
Calculated LDL-C in mg/dL	201 mg/dL STANDARD_DEVIATION 43.4 • n=5 Participants	196.3 mg/dL STANDARD_DEVIATION 57.9 • n=7 Participants	197.8 mg/dL STANDARD_DEVIATION 53.4 • n=5 Participants
Calculated low density lipoprotein cholesterol (LDL-C) in mmol/L	5.205 mmol/L STANDARD_DEVIATION 1.125 • n=5 Participants	5.083 mmol/L STANDARD_DEVIATION 1.499 • n=7 Participants	5.123 mmol/L STANDARD_DEVIATION 1.382 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off- treatment.

Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis	-6.6 percent change Standard Error 4.9	-45.7 percent change Standard Error 3.5

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.

Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection (on-treatment analysis).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	-6.6 percent change Standard Error 5	-45.5 percent change Standard Error 3.5

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	-6.6 percent change Standard Error 4.6	-46.9 percent change Standard Error 3.2

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: mITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis	-6.6 percent change Standard Error 4.6	-46.9 percent change Standard Error 3.2

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=34 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=69 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis	-8.7 percent change Standard Error 3.8	-39 percent change Standard Error 2.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment (Apo B mITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=34 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=69 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis	-8.7 percent change Standard Error 3.9	-38.9 percent change Standard Error 2.8

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	-6.2 percent change Standard Error 4.3	-41.9 percent change Standard Error 3.1

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the mITT population with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis	-6.1 percent change Standard Error 4.3	-41.7 percent change Standard Error 3.1

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment (total-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	-4.8 percent change Standard Error 3.6	-33.2 percent change Standard Error 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Apo B ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=34 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=69 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	-9 percent change Standard Error 3.7	-39.2 percent change Standard Error 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Non-HDL-C ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	-6.9 percent change Standard Error 4.3	-41.4 percent change Standard Error 3

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Total-C ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	-5.2 percent change Standard Error 3.5	-33 percent change Standard Error 2.4

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from week 4 to week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis	-3 percent change Standard Error 5.9	-42.1 percent change Standard Error 4.2

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT population.

Very high CV risk participants: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents. High CV risk participants: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to \<60 ml/minute/1.73 m\^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of \>2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or a family history of premature CHD). Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis	5.7 percentage of participants	41.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: mITT population.

Adjusted percentages at Week 24 from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - On-Treatment Analysis	5.7 percentage of participants	41.4 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis	-8.7 percent change Standard Error 5	-23.5 percent change Standard Error 3.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the ITT population with one baseline and at least one post-baseline HDL-C value on-or off-treatment (HDL-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	3.9 percent change Standard Error 2.7	7.5 percent change Standard Error 1.9

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	-1.9 percent change Standard Error 4.8	-10.5 percent change Standard Error 3.3

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on-or off-treatment (Apo A-1 ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=34 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=69 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis	2 percent change Standard Error 2.1	5.6 percent change Standard Error 1.5

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis	-1.5 percent change Standard Error 5.1	-23.2 percent change Standard Error 3.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: HDL-C ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	8.0 percent change Standard Error 3.4	7.9 percent change Standard Error 2.4

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	-4.4 percent change Standard Error 5.1	-9.4 percent change Standard Error 3.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Apo A-1 ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=34 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=69 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis	1.1 percent change Standard Error 2.2	4.6 percent change Standard Error 1.5

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT population.

Adjusted percentages at Week 24 from multiple imputation approach including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	2.9 percentage of participants	32.4 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: mITT population.

Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	2.9 percentage of participants	32.6 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 52

Population: mITT population.

Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis	-2.9 percent change Standard Error 6.1	-42.0 percent change Standard Error 4.4

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 78

Population: ITT population.

Adjusted LS means and standard errors at Week 78 from MMRM model including all available post-baseline data from Week 4 to Week 78 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis	1.2 percent change Standard Error 6.4	-37.9 percent change Standard Error 4.5

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 78

Population: mITT population.

Adjusted LS means and standard errors at Week 78 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 78 i.e. up to 21 days after last injection.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=35 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=71 Participants Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis	-0.2 percent change Standard Error 6.2	-40.9 percent change Standard Error 4.5

Adverse Events

Placebo Q2W

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Alirocumab 150 Q2W

Serious events: 10 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Q2W n=35 participants at risk Participants exposed to placebo Q2W on top of stable LMT (mean exposure of 71 weeks).	Alirocumab 150 Q2W n=72 participants at risk Participants exposed to Alirocumab 150 mg Q2W on top of stable LMT (mean exposure of 68 weeks).
Infections and infestations Bronchitis	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Diverticulitis	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Immune system disorders Anaphylactic reaction	2.9% 1/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	0.00% 0/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Nervous system disorders Carpal tunnel syndrome	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Cardiac disorders Myocardial infarction	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	2.8% 2/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Cardiac disorders Acute coronary syndrome	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Cardiac disorders Acute myocardial infarction	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Cardiac disorders Angina pectoris	2.9% 1/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Cardiac disorders Cardiac failure	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Hepatobiliary disorders Biliary colic	2.9% 1/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	0.00% 0/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	2.9% 1/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	0.00% 0/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Renal and urinary disorders Renal failure	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Renal and urinary disorders Renal colic	2.9% 1/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	0.00% 0/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).

Measure	Placebo Q2W n=35 participants at risk Participants exposed to placebo Q2W on top of stable LMT (mean exposure of 71 weeks).	Alirocumab 150 Q2W n=72 participants at risk Participants exposed to Alirocumab 150 mg Q2W on top of stable LMT (mean exposure of 68 weeks).
Infections and infestations Nasopharyngitis	11.4% 4/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	13.9% 10/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Influenza	2.9% 1/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	12.5% 9/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Bronchitis	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 4/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Urinary tract infection	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.9% 5/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Sinusitis	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 4/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Upper respiratory tract infection	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 4/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Nervous system disorders Dizziness	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.9% 5/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Nervous system disorders Headache	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.9% 5/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Ear and labyrinth disorders Vertigo	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.4% 1/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Gastrointestinal disorders Diarrhoea	8.6% 3/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 4/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Gastrointestinal disorders Vomiting	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 4/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Gastrointestinal disorders Nausea	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	2.8% 2/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Gastrointestinal disorders Dyspepsia	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	0.00% 0/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Musculoskeletal and connective tissue disorders Myalgia	8.6% 3/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 4/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
General disorders Injection site reaction	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	8.3% 6/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
General disorders Fatigue	0.00% 0/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.9% 5/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Investigations Blood uric acid increased	5.7% 2/35 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	0.00% 0/72 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).