Trial Outcomes & Findings for Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease (NCT NCT02228460)

NCT ID: NCT02228460

Last Updated: 2019-12-17

Results Overview

Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 11 participants
• Primary outcome timeframe: Baseline, Week 26
• Results posted on: 2019-12-17

Participant Flow

Participants were enrolled in the study at 8 centers in 5 countries between 11 November 2014 and 06 September 2016. A total of 14 participants were screened in the study.

Out of 14 screened participants, 11 participants were enrolled and treated in the study.

Participant milestones

Measure	GZ/SAR402671 GZ/SAR402671 15 milligram (mg) once daily, orally for 26 weeks.
Overall Study STARTED	11
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	GZ/SAR402671 GZ/SAR402671 15 milligram (mg) once daily, orally for 26 weeks.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	1

Baseline Characteristics

Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease

Baseline characteristics by cohort

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Age, Continuous	26.5 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on full analysis set (FAS) that included all participants who received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 1 / Week 26 Score: 1	4 Participants
Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 1 / Week 26 Score: 2	1 Participants
Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 2 / Week 26 Score: 1	3 Participants
Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 2 / Week 26 Score: 2	1 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Change from Baseline in GL-3 score was obtained by subtracting Baseline value from post-baseline value at Week 26. A negative change from Baseline indicates less severe condition at Week 26.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Mean Change From Baseline at Week 26 in Skin GL-3 Score in Superficial Skin Capillary Endothelium	-0.22 score on a scale Interval -0.73 to 0.29

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Change from Baseline in plasma GL-3 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of GL-3 in plasma was determined using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline in Plasma GL-3 Concentration at Week 26	-3.62 mcg/mL Standard Deviation 1.07

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Change from Baseline in plasma Lyso-GL-3 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of lyso-GL-3 in plasma was determined using a validated LC-MS/MS method.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso-GL-3) Concentration at Week 26	-30.99 ng/mL Standard Deviation 22.83

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Change from Baseline in plasma GL-1 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of GL-1 in plasma was determined using a validated LC-MS/MS method.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration at Week 26	-3.26 mcg/mL Standard Deviation 1.43

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Endothelial Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 1 / Week 26 Score: 1	1 Participants
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Endothelial Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 2 / Week 26 Score: 1	2 Participants
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Endothelial Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 2 / Week 26 Score: 2	6 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 1.5 / Week 26 Score: 1.5	2 Participants
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 2 / Week 26 Score: 2	7 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline at Week 26 in Skin GL-3 Score in Perineurium Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 1 / Week 26 Score: 2	1 Participants
Change From Baseline at Week 26 in Skin GL-3 Score in Perineurium Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 Baseline Score: 2 / Week 26 Score: 2	8 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.

Change from Baseline in urine GL-3 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of GL-3 in urine was determined using a validated LC-MS/MS method.

Outcome measures

Measure	GZ/SAR402671 n=8 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Change From Baseline in Urine Globotriaosylceramide (GL-3) Concentration at Week 26	-0.25 mg/mmol Cr Standard Deviation 0.19

SECONDARY outcome

Timeframe: From Baseline up to 212 days

Population: Analysis was performed on safety population which included all enrolled participants who received at least 1 dose of study drug.

Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened during on-treatment period (period from the first administration of study drug through the last administration of the study drug plus 30 days or end of study participation for participant, whichever occurs first).

Outcome measures

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	9 Participants

SECONDARY outcome

Timeframe: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)

Population: Analysis was performed on PK population which included all participants for whom the primary PK data were considered sufficient and interpretable. Here, 'number analyzed' = participants with available data at specified time-point.

Maximum plasma concentration observed for study drug was reported.

Outcome measures

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671 Day 1	24.7 ng/mL Standard Deviation 5.89
Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671 Day 182	192.0 ng/mL Standard Deviation 96.4

SECONDARY outcome

Timeframe: Predose on Days 14, 28, 56, 84, 126, and 182

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point.

Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.

Outcome measures

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671 Day 14	152.0 ng/mL Standard Deviation 68.9
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671 Day 28	165.0 ng/mL Standard Deviation 66.1
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671 Day 56	182.0 ng/mL Standard Deviation 90.3
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671 Day 84	164.0 ng/mL Standard Deviation 124.0
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671 Day 126	175.0 ng/mL Standard Deviation 94.7
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671 Day 182	164.0 ng/mL Standard Deviation 89.4

SECONDARY outcome

Timeframe: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point.

Tmax was defined as time to reach maximum plasma concentration of study drug.

Outcome measures

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Time to Reach Maximum Plasma Drug Concentration (Tmax) of GZ/SAR402671 Day 1	8.00 hours Interval 1.07 to 24.0
PK: Time to Reach Maximum Plasma Drug Concentration (Tmax) of GZ/SAR402671 Day 182	4.00 hours Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point.

Area under the plasma concentration versus time curve of study drug from time 0 to 24 hours (AUC0-24) was calculated using the trapezoidal method over the dosing interval.

Outcome measures

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Area Under Plasma Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24) of GZ/SAR402671 Day 1	476 ng*hour/mL Standard Deviation 125
PK: Area Under Plasma Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24) of GZ/SAR402671 Day 182	4110 ng*hour/mL Standard Deviation 2090

SECONDARY outcome

Timeframe: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point.

Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half. The t1/2z was estimated based on 24-hour post-dose PK.

Outcome measures

Measure	GZ/SAR402671 n=11 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Terminal Half-life (t1/2z) of GZ/SAR402671 Day 1	86.8 hours Standard Deviation 39.6
PK: Terminal Half-life (t1/2z) of GZ/SAR402671 Day 182	128.0 hours Standard Deviation 59.0

SECONDARY outcome

Timeframe: Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Apparent total body clearance at steady state was a quantitative measure of rate of clearance of drug from the blood following oral administration, and is described in terms of volume of fluid clear of drug per time unit (eg, mL/min).

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Apparent Total Body Clearance of GZ/SAR402671 at Steady State (CLss/F)	7490 mL/hour Standard Deviation 10900

SECONDARY outcome

Timeframe: Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182

Population: Since the percent extrapolation of AUC for all participants was \>30%, AUC could not be determined and hence, Vss/F could not be calculated.

Volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of drug.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0-24 hours on Day 182

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Ae0-24 was the cumulated amount of study drug excreted in urine during the time interval of 0 to 24 hours.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Cumulated Amount of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (Ae0-24)	3210.0 mcg Standard Deviation 1640.0

SECONDARY outcome

Timeframe: 0-24 hours on Day 182

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

fe0-24 was the fraction of dose excreted in urine during the time interval of 0 to 24 hours.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Percentage of Dose of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (fe0-24)	21.4 percentage of dose Standard Deviation 10.9

SECONDARY outcome

Timeframe: 0-24 hours on Day 182

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

CLR was calculated by dividing the cumulative amount of drug excreted in urine during the dosing interval of 0-24 hours by area under the plasma drug concentration time-curve during the dosing interval of 0-24 hours.

Outcome measures

Measure	GZ/SAR402671 n=9 Participants GZ/SAR402671 15 mg once daily, orally for 26 weeks.
PK: Renal Clearance (CLR) of GZ/SAR402671 From 0 to 24 Hours	925 mL/hour Standard Deviation 407

Adverse Events

GZ/SAR402671

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	GZ/SAR402671 n=11 participants at risk GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Blood and lymphatic system disorders Haemolysis	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Floppy infant	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders Depressed mood	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.

Other adverse events

Measure	GZ/SAR402671 n=11 participants at risk GZ/SAR402671 15 mg once daily, orally for 26 weeks.
Skin and subcutaneous tissue disorders Angiokeratoma	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Tinnitus	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Blepharitis	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Chalazion	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Eye pain	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Lacrimation increased	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Lenticular opacities	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Retinal vascular disorder	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Vision blurred	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dry mouth	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophageal discomfort	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Toothache	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
General disorders Fatigue	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
General disorders Feeling hot	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
General disorders Influenza like illness	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
General disorders Non-cardiac chest pain	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
General disorders Pyrexia	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Ear infection	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Rhinitis	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Muscle strain	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Wound	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Investigations Electrocardiogram T wave abnormal	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Investigations Electrocardiogram abnormal	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Investigations Nuclear magnetic resonance imaging brain abnormal	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Investigations Vibration test abnormal	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle twitching	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Amnesia	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Headache	36.4% 4/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Hypoaesthesia	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Migraine	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Sinus headache	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders White matter lesion	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders Depressed mood	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.2% 2/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Acne	9.1% 1/11 • Baseline up to 212 days Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
• Publication restrictions are in place

Restriction type: OTHER