Trial Outcomes & Findings for Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia (NCT NCT01644474)

NCT ID: NCT01644474

Last Updated: 2015-11-06

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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 103 participants
• Primary outcome timeframe: From Baseline to Week 24
• Results posted on: 2015-11-06

Participant Flow

The study was conducted at 8 centers in 4 countries. A total of 204 participants were screened between July 2012 and November 2012, 101 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.

Randomization was stratified according to the diabetes mellitus status. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1 ratio ( alirocumab:ezetimibe) after confirmation of selection criteria. 103 participants were randomized.

Participant milestones

Measure	Ezetimibe 10 mg Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Study STARTED	51	52
Overall Study Treated	51	52
Overall Study COMPLETED	44	44
Overall Study NOT COMPLETED	7	8

Reasons for withdrawal

Measure	Ezetimibe 10 mg Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Study Poor compliance to protocol	1	0
Overall Study Consent withdrawn by participant	0	1
Overall Study Participant moved	0	1
Overall Study Adverse Event	4	5
Overall Study Site scheduling error	1	1
Overall Study Protocol Violation	1	0

Baseline Characteristics

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia

Baseline characteristics by cohort

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Total n=103 Participants Total of all reporting groups
Age, Continuous	59.6 years STANDARD_DEVIATION 5.3 • n=5 Participants	60.8 years STANDARD_DEVIATION 4.6 • n=7 Participants	60.2 years STANDARD_DEVIATION 5.0 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants
Calculated LDL-C in mmol/L	3.58 mmol/L STANDARD_DEVIATION 0.6 • n=5 Participants	3.65 mmol/L STANDARD_DEVIATION 0.7 • n=7 Participants	3.62 mmol/L STANDARD_DEVIATION 0.7 • n=5 Participants
Calculated LDL-C in mg/dL	138.3 mg/dL STANDARD_DEVIATION 24.5 • n=5 Participants	141.1 mg/dL STANDARD_DEVIATION 27.1 • n=7 Participants	139.7 mg/dL STANDARD_DEVIATION 25.8 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis	-15.6 percent change Standard Error 3.1	-47.2 percent change Standard Error 3.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	-19.6 percent change Standard Error 2.6	-48.1 percent change Standard Error 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=46 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=48 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis	-11.0 percent change Standard Error 2.4	-36.7 percent change Standard Error 2.3

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	-15.1 percent change Standard Error 2.9	-40.6 percent change Standard Error 2.8

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	-10.9 percent change Standard Error 2.2	-29.6 percent change Standard Error 2.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=46 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=48 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	-11.7 percent change Standard Error 2.1	-37.3 percent change Standard Error 2.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	-16.7 percent change Standard Error 2.4	-42.5 percent change Standard Error 2.3

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	-12.0 percent change Standard Error 1.7	-30.3 percent change Standard Error 1.7

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population.

Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis	32.2 percentage of participants	88.1 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population.

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

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	2.4 percentage of participants	59.4 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis	-12.3 percent change Standard Error 3.8	-16.7 percent change Standard Error 3.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	1.6 percent change Standard Error 1.9	6.0 percent change Standard Error 1.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	1.6 percent change Standard Error 2.0	9.0 percent change Standard Error 2.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis	-14.2 percent change Standard Error 3.7	-17.2 percent change Standard Error 3.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	-10.8 percent change Standard Error 4.3	-11.9 percent change Standard Error 4.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=51 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=52 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	-2.3 percent change Standard Error 3.5	-12.2 percent change Standard Error 3.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=46 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=48 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis	-0.6 percent change Standard Error 1.6	4.7 percent change Standard Error 1.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Ezetimibe 10 mg n=46 Participants Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.	Alirocumab 75/Up to 150 mg Q2W n=48 Participants SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis	-2.2 percent change Standard Error 1.4	2.3 percent change Standard Error 1.4

Adverse Events

Ezetimibe 10 mg

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Alirocumab 75/Up150 mg Q2W

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ezetimibe 10 mg n=51 participants at risk Participants exposed to Ezetimibe 10 mg (mean exposure of 22 weeks).	Alirocumab 75/Up150 mg Q2W n=52 participants at risk Participants exposed to Alirocumab 75 mg/Up to 150 mg Q2W (mean exposure of 22 weeks).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	1.9% 1/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Musculoskeletal and connective tissue disorders Bone erosion	2.0% 1/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	0.00% 0/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).

Other adverse events

Measure	Ezetimibe 10 mg n=51 participants at risk Participants exposed to Ezetimibe 10 mg (mean exposure of 22 weeks).	Alirocumab 75/Up150 mg Q2W n=52 participants at risk Participants exposed to Alirocumab 75 mg/Up to 150 mg Q2W (mean exposure of 22 weeks).
Infections and infestations Nasopharyngitis	15.7% 8/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	23.1% 12/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Infections and infestations Influenza	5.9% 3/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	11.5% 6/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Infections and infestations Upper respiratory tract infection	9.8% 5/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	3.8% 2/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Infections and infestations Urinary tract infection	5.9% 3/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	0.00% 0/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Nervous system disorders Headache	3.9% 2/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	5.8% 3/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Nervous system disorders Dizziness	5.9% 3/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	1.9% 1/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Gastrointestinal disorders Diarrhoea	3.9% 2/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	11.5% 6/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Gastrointestinal disorders Nausea	5.9% 3/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	5.8% 3/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Musculoskeletal and connective tissue disorders Arthralgia	3.9% 2/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	5.8% 3/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).
Musculoskeletal and connective tissue disorders Back pain	5.9% 3/51 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).	1.9% 1/52 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (from the first dose of double-blind study drug administration (capsule or injection, whichever came first) up to the day of the last double-blind injection + 70 days).

Additional Information

Trial Transparency Team

Sanofi

Email: Contact-US@sanofi.com

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