Trial Outcomes & Findings for Evaluation of the Long-term Safety, Pharmacodynamics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-Naïve Adult Male Patients With Fabry Disease (NCT NCT02489344)

Last Updated: 2021-03-23

Results Overview

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 TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurred first). For this analysis, baseline was defined as initial ACT13739 study baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Results posted on

2021-03-23

Participant Flow

Participants who successfully completed 26 weeks of treatment in prior ACT13739 study (NCT02228460) were eligible to continue their treatment for up to 30 additional months in this extension study LTS14116. Eleven participants had enrolled and were treated in ACT13739 study, and 9 completed study. Of these 9 participants, 8 entered extension study.

In extension study, participants continued on same dose regimen they had received in initial study. Two participants in LTS14116 completed treatment and did not discontinue early, but are counted as not completed study due to no record of completion.

Participant milestones

Participant milestones
Measure	GZ/SAR402671 Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
ACT13739 (Initial Study): 26 Weeks STARTED	11
ACT13739 (Initial Study): 26 Weeks COMPLETED	9
ACT13739 (Initial Study): 26 Weeks NOT COMPLETED	2
LTS14116 (Extension Study): 31 Months STARTED	8
LTS14116 (Extension Study): 31 Months COMPLETED	5
LTS14116 (Extension Study): 31 Months NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	GZ/SAR402671 Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
ACT13739 (Initial Study): 26 Weeks Adverse Event	1
ACT13739 (Initial Study): 26 Weeks Lost to Follow-up	1
LTS14116 (Extension Study): 31 Months Adverse Event	1
LTS14116 (Extension Study): 31 Months Treatment completed/Study not completed	2

Baseline Characteristics

Evaluation of the Long-term Safety, Pharmacodynamics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-Naïve Adult Male Patients With Fabry Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
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
Race/Ethnicity, Customized Race · Caucasian/White	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Population: Analysis was performed on safety population: all participants who received at least 1 dose of investigational medicinal product (IMP) during the ACT13739 study. All data collected during ACT13739 and LTS14116 studies were included in analysis.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	9 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Population: Analysis was performed on safety population: all participants who received at least 1 dose of IMP during the ACT13739 study. All data collected during ACT13739 and LTS14116 studies were included in analysis.

Criteria for potentially clinically significant abnormalities: * Hemoglobin: less than or equal to (\<=) 115 grams per liter (g/L); greater than or equal to (\>=)185 g/L; decreased from baseline (DFB) \>=20 g/L * Hematocrit: \<=0.37 volume/volume (v/v); \>=0.55 v/v * Erythrocytes: \>=6 Tera/L * Platelets: lesser than (\<) 100 Giga/L; \>=700 Giga/L * Leukocytes: \<3.0 Giga/L (Non-Black \[NB\]) or \<2.0 Giga/L (Black \[B\]); \>=16.0 Giga/L * Neutrophils: \<1.5 Giga/L (NB) or \<1.0 Giga/L (B); * Lymphocytes: greater than (\>) 4.0 Giga/L * Monocytes: \>0.7 Giga/L * Basophils: \>0.1 Giga/L * Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L) For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Hemoglobin <=115 g/L	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Hemoglobin >=185 g/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Hemoglobin DFB >=20 g/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Hematocrit <=0.37 v/v	6 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Hematocrit >0.55 v/v	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Erythrocytes: >=6 Tera/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Platelets <100 Giga/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Platelets >=700 Giga/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Leukocytes <3.0 Giga/L (NB) or <2.0 Giga/L (B)	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Leukocytes >=16.0 Giga/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Lymphocytes >4.0 Giga/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Monocytes >0.7 Giga/L	2 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Basophils >0.1 Giga/L	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L)	0 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria for potentially clinically significant abnormalities: * Sodium: \<=129 millimoles (mmol)/L; \>=160 mmol/L * Potassium: \<3 mmol/L; \>=5.5 mmol/L * Chloride: \<80 mmol/L; \>115 mmol/L.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Sodium <=129 mmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Sodium >=160 mmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Potassium <3 mmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Potassium >=5.5 mmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Chloride <80 mmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Chloride >115 mmol/L	0 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria for potentially clinically significant abnormalities: * Alanine Aminotransferase (ALT): \>3 ULN; \>5 ULN; \>10 ULN and \>20 ULN * Aspartate aminotransferase (AST): \>3 ULN; \>5 ULN; \>10 ULN and \>20 ULN * Alkaline phosphatase: \>1.5 ULN * Bilirubin: \>1.5 ULN; \>2 ULN.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >3 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >5 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >10 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >20 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >3 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >5 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >10 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >20 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters Alkaline Phosphatase >1.5 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters Bilirubin >1.5 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters Bilirubin >2 ULN	0 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria for potentially clinically significant abnormalities: * Glucose: \<=3.9 mmol/L and \< lower limits of normal (LLN); \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]) * Lipase: \>= 3 ULN * C Reactive Protein (CRP): \> 2 ULN or \> 10 milligrams (mg)/L (if ULN not provided).

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters Glucose <=3.9 mmol/L and <LLN	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters Albumin <=25 g/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters Lipase >=3 ULN	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters CRP >2 ULN or >10 mg/L (if ULN not provided)	2 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria for potentially clinically significant abnormalities: * Creatinine: \>=150 micromoles per liter (mcmol/L) (Adults); \>=30% change from baseline; \>= 100% change from baseline * Blood urea nitrogen: \>=17 mmol/L * Urate: \<120 mcmol/L; \>408 mcmol/L For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine >=150 mcmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine >=30% change from baseline	2 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine >=100% change from baseline	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Blood Urea Nitrogen >=17 mmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Urate <120 mcmol/L	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Urate >408 mcmol/L	5 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria with potentially clinically significant urine abnormalities: pH: \<= 4.6; pH: \>= 8.0

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Urinalysis pH <= 4.6	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Urinalysis pH >= 8.0	0 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria for potentially clinically significant vital sign abnormalities: * Systolic blood pressure (SBP) supine: \<=95 millimeters of mercury (mmHg) and DFB \>=20 mmHg; \>=160 mmHg and increase from baseline (IFB) \>=20 mmHg * Diastolic blood pressure (DBP) supine: \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg * Heart rate (HR) supine: \<=50 beats per minute (bpm) and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm * Weight: \>=5% DFB; \>=5% IFB For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities SBP (supine) <=95 mmHg and DFB >=20 mmHg	0 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities SBP (supine) >=160 mmHg and IFB >=20 mmHg	0 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities DBP (supine) <=45 mmHg and DFB >=10 mmHg	0 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities DBP (supine) >=110 mmHg and IFB >=10 mmHg	0 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities HR (supine) <=50 bpm and DFB >= 20 bpm	1 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities HR (supine) >=120 bpm and IFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities Weight >=5% DFB	3 Participants
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities Weight >=5% IFB	2 Participants

PRIMARY outcome

Timeframe: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline

Criteria for potentially clinically significant ECG abnormalities: * ECG mean HR: \<30 bpm; \<30 bpm and DFB \>=20 bpm; \<40 bpm; \<40 bpm and DFB \>=20 bpm; \<50 bpm; \<50 bpm and DFB \>=20 bpm; \>90 bpm; \<90 bpm and DFB \>=20 bpm; \>100 bpm; \<100 bpm and DFB \>=20 bpm; \>120 bpm; \<120 bpm and DFB \>=20 bpm * PR Interval: \>200 milliseconds (ms); \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB \>=25% * QRS duration: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25% * QTc Bazett (QTcB) interval: \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms, IFB \>60 ms * QTc Fridericia (QTc F): \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms * QT Interval: \>500 ms For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <30 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <30 bpm and DFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <40 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <40 bpm and DFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <50 bpm	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <50 bpm and DFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR >90 bpm	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <90 bpm and DFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR >100 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <100 bpm and DFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR >120 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities ECG Mean HR <120 bpm and DFB >=20 bpm	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities PR interval >200 ms	2 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities PR interval >200 ms and IFB >=25%	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities PR interval >220 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities PR interval >220 ms and IFB >=25%	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities PR >240 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities PR interval >240 ms and IFB >=25%	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QRS duration >110 ms	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QRS duration >110 ms and IFB >=25%	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QRS duration >120 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QRS duration >120 ms and IFB >=25%	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcB interval >450 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcB interval >480 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTc B interval >500 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcB interval IFB >30 and <=60 ms	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcB interval IFB >60 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcF interval >450 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTc F interval >480 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcF interval >500 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcF interval IFB >30 and <=60 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcF interval IFB >60 ms	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QT interval >500 ms	0 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Population: Analysis was performed on full analysis set: all participants who received at least 1 dose of IMP during the ACT13739 study. All data collected during ACT13739 and LTS14116 studies were included in analysis. Here, 'number analyzed' = participants with available data for each specified category.

Change from baseline in plasma GL-3 was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104, and 156. Concentration of GL-3 in plasma was determined using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 26	-3.62 micrograms per milliliter (mcg/mL) Standard Deviation 1.07
Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 52	-5.06 micrograms per milliliter (mcg/mL) Standard Deviation 1.04
Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 104	-6.32 micrograms per milliliter (mcg/mL) Standard Deviation 2.53
Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 156	-6.97 micrograms per milliliter (mcg/mL) Standard Deviation 2.27

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Change from baseline in plasma GL-3 was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104, and 156. Concentration of lyso-GL-3 in plasma was determined using a validated LC-MS/MS method. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 26	-30.99 nanograms per mL (ng/mL) Standard Deviation 22.83
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 52	-37.10 nanograms per mL (ng/mL) Standard Deviation 20.69
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 104	-39.84 nanograms per mL (ng/mL) Standard Deviation 18.12
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso GL-3) Concentration at Weeks 26, 52, 104, and 156 Week 156	-48.13 nanograms per mL (ng/mL) Standard Deviation 15.65

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Change from baseline in plasma GL-1 was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104, and 156. Concentration of GL-1 in plasma was determined using a validated LC-MS/MS method. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration At Weeks 26, 52, 104, and 156 Week 52	-3.58 mcg/mL Standard Deviation 0.85
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration At Weeks 26, 52, 104, and 156 Week 26	-3.26 mcg/mL Standard Deviation 1.43
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration At Weeks 26, 52, 104, and 156 Week 104	-3.70 mcg/mL Standard Deviation 0.85
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration At Weeks 26, 52, 104, and 156 Week 156	-3.23 mcg/mL Standard Deviation 1.11

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Change from baseline in plasma GM3 was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104, and 156. Concentration of GM3 in plasma was determined using a validated LC-MS/MS method. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Plasma Monosialodihexosylganglioside (GM3) Concentration At Weeks 26, 52, 104, and 156 Week 52	-8.84 mcg/mL Standard Deviation 4.55
Change From Baseline in Plasma Monosialodihexosylganglioside (GM3) Concentration At Weeks 26, 52, 104, and 156 Week 104	-9.92 mcg/mL Standard Deviation 3.26
Change From Baseline in Plasma Monosialodihexosylganglioside (GM3) Concentration At Weeks 26, 52, 104, and 156 Week 156	-8.12 mcg/mL Standard Deviation 5.37
Change From Baseline in Plasma Monosialodihexosylganglioside (GM3) Concentration At Weeks 26, 52, 104, and 156 Week 26	-10.77 mcg/mL Standard Deviation 6.02

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Change from baseline in urine GL-3 was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104, and 156. Concentration of GL-3 in urine was determined using a validated LC-MS/MS method. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Urine GL-3 Concentration At Weeks 26, 52, 104, and 156 Week 26	-0.25 mg/mmol creatinine (Cr) Standard Deviation 0.19
Change From Baseline in Urine GL-3 Concentration At Weeks 26, 52, 104, and 156 Week 52	-0.20 mg/mmol creatinine (Cr) Standard Deviation 0.22
Change From Baseline in Urine GL-3 Concentration At Weeks 26, 52, 104, and 156 Week 104	-0.18 mg/mmol creatinine (Cr) Standard Deviation 0.22
Change From Baseline in Urine GL-3 Concentration At Weeks 26, 52, 104, and 156 Week 156	-0.18 mg/mmol creatinine (Cr) Standard Deviation 0.27

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Change from baseline in high sensitivity cardiac troponin T was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104, and 156. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in High Sensitivity Cardiac Troponin T At Weeks 26, 52, 104, and 156 Week 26	0.0000 mcg/L Standard Deviation 0.0000
Change From Baseline in High Sensitivity Cardiac Troponin T At Weeks 26, 52, 104, and 156 Week 52	0.0105 mcg/L Standard Deviation 0.0241
Change From Baseline in High Sensitivity Cardiac Troponin T At Weeks 26, 52, 104, and 156 Week 104	-0.0015 mcg/L Standard Deviation 0.0000
Change From Baseline in High Sensitivity Cardiac Troponin T At Weeks 26, 52, 104, and 156 Week 156	0.0006 mcg/L Standard Deviation 0.0027

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 12, 26, and 156 post-ACT13739 baseline

Change from baseline in podocyturia was obtained by subtracting baseline value from post-baseline value at Weeks 12, 26, and 156. Urine samples were processed to identify podocyte (podocalyxin, PCX) and parietal cell (claudin 1, CL1) markers. PCX +/CL1 negative cells were identified as podocytes and PCX +/CL1 positive cells as parietal cells with podocyte phenotype. All counts were corrected for urine Cr. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Podocyturia Counts (Per Milligram of Creatinine) At Weeks 12, 26, and 156 Week 12	-1.40 Count of podocytes/mg Cr Standard Deviation 2.69
Change From Baseline in Podocyturia Counts (Per Milligram of Creatinine) At Weeks 12, 26, and 156 Week 26	-1.65 Count of podocytes/mg Cr Standard Deviation 2.97
Change From Baseline in Podocyturia Counts (Per Milligram of Creatinine) At Weeks 12, 26, and 156 Week 156	-2.73 Count of podocytes/mg Cr Standard Deviation 3.97

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline

Skin biopsies were performed for the scoring of GL-3 accumulation/inclusions by light microscopy. Three independent pathologists scored GL-3 clearance by 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 Weeks 12, 26, 52, and 156 GL-3 score. Shift to lower score from baseline indicated less severe condition at that respective time point. Any shift category of Baseline score/Week score that was not observed (no participant had data in the category) was not reported. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 12 Score:1	4 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 12 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 12 Score:1	3 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 12 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 26 Score:1	4 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 26 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 26 Score:1	3 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 26 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 52 Score:1	3 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:1	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 156 Score:0	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Sore:1/Week 156 Score:1	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:1	3 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 12 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 12 Score:1	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 12 Score:2	6 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 26 Score:1	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 26 Score:1	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 26 Score:2	6 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:1	3 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:1.5	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Sore:2/Week 52 Score:2	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 156 Score:1	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:0.5	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:1	3 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:2	1 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1.5/Week 12 Score:2	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 12 Score:2	7 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1.5/Week 26 Score:1.5	2 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 26 Score:2	7 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1.5/Week 52 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:2	4 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1.5/Week 156 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:1	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:1.5	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:2	3 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 12 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:1.5	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:2	3 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 156 Score:1	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:1.5	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 156 Score:2	4 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 12 Score:2	8 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 26 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 26 Score:2	8 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:1/Week 52 Score:2	1 Participants
Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score Baseline Score:2/Week 52 Score:1	1 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

The SF-36 health survey is a participant-reported survey to measure participant's health. It is a 36-item questionnaire used to measure 8 various aspects of health (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health). The score range for each of the 8 aspects was from 0 (maximum disability) to 100 (no disability), higher scores indicating good health condition. Responses on the SF-36 were also used to calculate 2 summary scores: Physical component score (PCS) and mental component score (MCS). The score range for each of these 2 summary scores was from 0 (maximum disability) to 100 (no disability), where higher score indicated less disability or good health condition. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Mental Component Summary: Week 156	2.87 units on a scale Standard Deviation 14.17
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Physical Component Summary: Week 26	8.39 units on a scale Standard Deviation 6.88
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Physical Component Summary: Week 52	7.70 units on a scale Standard Deviation 7.76
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Mental Component Summary: Week 26	-3.31 units on a scale Standard Deviation 20.34
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Physical Component Summary: Week 104	9.72 units on a scale Standard Deviation 9.02
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Physical Component Summary: Week 156	5.30 units on a scale Standard Deviation 11.83
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Mental Component Summary: Week 52	1.69 units on a scale Standard Deviation 8.27
Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156 Mental Component Summary: Week 104	6.48 units on a scale Standard Deviation 8.14

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · Yes	6 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · No	6 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · Yes	5 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · No	7 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · Yes	4 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · No	5 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · No	5 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · Yes	2 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · No	5 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · No	5 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · No	8 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · Yes	3 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · No	8 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · Yes	2 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · No	7 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · Yes	2 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · No	6 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · Yes	3 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · Yes	2 Participants
Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · Yes	2 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to mark the severity of the abdominal pain in past 10 days (before each of the specified time points) on a visual analogue scale (VAS). The scale ranged from 0% (no pain) to 100% (very severe), where higher score indicated more severity. For this analysis, baseline was defined as initial ACT13739 study baseline. Standard deviation (SD) can only be calculated when there are more than 1 participant with data available. Thereby, applicable fields were left blank when SD was not calculable.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18	43.00 score on a 0-100 percent scale Standard Deviation 29.70
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline	52.50 score on a 0-100 percent scale Standard Deviation 20.50
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2	35.60 score on a 0-100 percent scale Standard Deviation 18.47
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4	29.75 score on a 0-100 percent scale Standard Deviation 20.07
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8	29.00 score on a 0-100 percent scale Standard Deviation 21.28
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12	40.00 score on a 0-100 percent scale Standard Deviation 21.21
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26	31.33 score on a 0-100 percent scale Standard Deviation 32.81
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52	21.00 score on a 0-100 percent scale
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104	21.00 score on a 0-100 percent scale
Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156	15.00 score on a 0-100 percent scale Standard Deviation 7.07

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to report the number of days they had abdominal pain in past 10 days (before each of the specified time points). Number of days with abdominal pain score was achieved by multiplying number of days with pain \* 10. The score ranges from 10 to 100, where higher score signifies more number of days with pain. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline	38.33 score on a scale Standard Deviation 31.89
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2	26.00 score on a scale Standard Deviation 20.74
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4	25.00 score on a scale Standard Deviation 20.82
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8	25.00 score on a scale Standard Deviation 23.80
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12	35.00 score on a scale Standard Deviation 7.07
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18	35.00 score on a scale Standard Deviation 21.21
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26	30.00 score on a scale Standard Deviation 34.64
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52	7.00 score on a scale Standard Deviation 12.12
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104	5.00 score on a scale Standard Deviation 7.07
Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156	20.00 score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to report the presence of abdominal distention in past 10 days (before each of the specified time points). Participants answered the question: "Do you currently suffer from abdominal distension (bloating, swelling or tight tummy)? \[Yes/No\]". For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · No	8 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · Yes	3 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · No	7 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · Yes	4 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · No	9 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · Yes	2 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · Yes	1 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · Yes	0 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · No	9 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · Yes	2 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · No	9 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · No	8 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · Yes	1 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · No	8 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · Yes	1 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · No	7 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · Yes	0 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · No	7 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · No	6 Participants
Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · Yes	1 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to mark the severity of the abdominal distension in past 10 days (before each of the specified time points) on a VAS. The scale ranged from 0% (no distention) to 100% (very severe), where higher score indicated more severity. For this analysis, baseline was defined as initial ACT13739 study baseline. The SD can only be calculated when there are more than 1 participant with data available. Thereby, applicable fields were left blank when SD was not calculable.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 2	38.67 score on a 0-100 percent scale Standard Deviation 38.42
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 4	21.00 score on a 0-100 percent scale Standard Deviation 26.15
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 26	80.00 score on a 0-100 percent scale
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Baseline	45.33 score on a 0-100 percent scale Standard Deviation 24.01
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 8	35.00 score on a 0-100 percent scale Standard Deviation 48.08
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 12	72.00 score on a 0-100 percent scale
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 18	69.00 score on a 0-100 percent scale
Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 Week 156	5.00 score on a 0-100 percent scale

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · Occasionally	5 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · Never	7 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · Never	6 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · Never	6 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156 · Often	0 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to mark their satisfaction over bowel habits in past 10 days (before each of the specified time points) on a VAS. The scale ranged from 0% (very happy) to 100% (very unhappy), where higher percentage indicated less satisfaction. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12	21.50 score on a 0-100 percent scale Standard Deviation 17.83
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52	19.00 score on a 0-100 percent scale Standard Deviation 17.05
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156	34.02 score on a 0-100 percent scale Standard Deviation 36.67
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline	26.55 score on a 0-100 percent scale Standard Deviation 19.09
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2	30.82 score on a 0-100 percent scale Standard Deviation 21.17
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4	36.09 score on a 0-100 percent scale Standard Deviation 28.68
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8	34.27 score on a 0-100 percent scale Standard Deviation 27.02
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18	23.89 score on a 0-100 percent scale Standard Deviation 21.29
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26	35.56 score on a 0-100 percent scale Standard Deviation 29.37
Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104	18.00 score on a 0-100 percent scale Standard Deviation 15.18

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to report the frequency of their bowel movement (per day or per week or per month) in past 10 days (before each of the specified time points) by answering the question "What is the most number of times you move your bowels per day/week/month?". Participants selected their preferred time unit (e.g., per day). Response provided by participants was converted to number of times per day for reporting the results. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18	2.17 number of bowel movements per day Standard Deviation 1.05
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52	2.08 number of bowel movements per day Standard Deviation 1.00
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline	2.36 number of bowel movements per day Standard Deviation 1.03
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2	2.00 number of bowel movements per day Standard Deviation 0.63
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4	2.00 number of bowel movements per day Standard Deviation 1.00
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8	1.74 number of bowel movements per day Standard Deviation 1.07
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12	2.04 number of bowel movements per day Standard Deviation 1.08
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26	2.16 number of bowel movements per day Standard Deviation 1.07
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104	1.96 number of bowel movements per day Standard Deviation 1.05
Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156	1.65 number of bowel movements per day Standard Deviation 0.61

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to report the frequency of their bowel movement (per day or per week or per month) in past 10 days (before each of the specified time points). Participants answered the question "What is the least number of times you move your bowels per day/week/month?". Participants selected their preferred time unit (e.g., per day). Response provided by participants was converted to number of times per day for reporting the results. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline	0.78 number of bowel movements per day Standard Deviation 0.56
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2	0.66 number of bowel movements per day Standard Deviation 0.43
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4	0.65 number of bowel movements per day Standard Deviation 0.62
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8	0.62 number of bowel movements per day Standard Deviation 0.64
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12	0.67 number of bowel movements per day Standard Deviation 0.65
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18	0.73 number of bowel movements per day Standard Deviation 0.65
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26	0.75 number of bowel movements per day Standard Deviation 0.40
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52	0.76 number of bowel movements per day Standard Deviation 0.72
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104	0.61 number of bowel movements per day Standard Deviation 0.49
Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156	0.92 number of bowel movements per day Standard Deviation 0.62

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline

Participants assessed their GI symptoms (abdominal pain, abdominal distention, bowel movements) by completing a questionnaire (modified version of the inflammatory bowel severity scoring system). Participants were asked to mark the influence of their GI symptoms of Fabry disease on life in past 10 days (before each of the specified time points) on a VAS. The scale ranged from 0% (no at all) to 100% (completely), where higher percentage indicated more influence of the GI symptoms of the disease on life. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Baseline	34.36 score on a 0-100 percent scale Standard Deviation 26.47
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 2	26.73 score on a 0-100 percent scale Standard Deviation 25.22
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 4	21.27 score on a 0-100 percent scale Standard Deviation 19.88
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 8	22.09 score on a 0-100 percent scale Standard Deviation 19.77
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 12	17.50 score on a 0-100 percent scale Standard Deviation 19.92
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 18	24.89 score on a 0-100 percent scale Standard Deviation 23.34
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 26	36.44 score on a 0-100 percent scale Standard Deviation 30.18
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 52	20.33 score on a 0-100 percent scale Standard Deviation 22.04
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 104	26.50 score on a 0-100 percent scale Standard Deviation 23.31
Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 Week 156	19.82 score on a 0-100 percent scale Standard Deviation 21.14

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Participants were asked to rate their stool consistency in past 10 days (before each of the specified time points) on a 7-point Bristol stool scale, according to the following types: 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces. Types 1 and 2 indicate constipation, types 3 and 4 indicate "ideal stools" (easiest to defecate), and 5-7 tending towards diarrhea. Frequency of each stool type was categorized as 'never', occasionally', or 'often'. For this analysis, baseline was defined as the initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 26 · Occasionally	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 26 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 104 · Occasionally	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 156 · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 156 · Occasionally	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 26 · Often	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 156 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Baseline · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 52 · Occasionally	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 26 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 104 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 104 · Never	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 104 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 104 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 156 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 156 · Occasionally	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 156 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Baseline · Never	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Baseline · Occasionally	9 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Baseline · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 26 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 26 · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 26 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 52 · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 52 · Occasionally	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 52 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 104 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 104 · Occasionally	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 104 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 156 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool type 5: Week 156 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Baseline · Occasionally	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Baseline · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 26 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 26 · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 26 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 52 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 52 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 104 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 104 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Baseline · Never	11 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 104 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 156 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 156 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 6: Week 156 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Baseline · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Baseline · Occasionally	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Baseline · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 26 · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 26 · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 52 · Never	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 52 · Occasionally	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 52 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 104 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 104 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 156 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 156 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 7: Week 156 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Baseline · Occasionally	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Baseline · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 26 · Never	8 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 52 · Never	6 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 52 · Occasionally	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 52 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 104 · Never	6 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 104 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 1: Week 156 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Baseline · Never	6 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Baseline · Occasionally	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Baseline · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 26 · Never	6 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 26 · Occasionally	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 26 · Often	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 52 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 52 · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 52 · Often	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 104 · Never	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 104 · Occasionally	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 104 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 156 · Never	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 156 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 2: Week 156 · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Baseline · Never	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Baseline · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Baseline · Often	6 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 26 · Never	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 26 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 26 · Often	5 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 52 · Never	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 52 · Occasionally	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 52 · Often	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 104 · Never	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 104 · Occasionally	6 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 104 · Often	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 156 · Never	0 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 156 · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 3: Week 156 · Often	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Baseline · Never	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Baseline · Occasionally	8 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Baseline · Often	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 26 · Never	2 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 26 · Occasionally	4 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 52 · Never	3 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 52 · Occasionally	1 Participants
Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 Stool Type 4: Week 52 · Often	3 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 104, and 156 post-ACT13739 baseline

The BDI-II Scale was a 21-item scoring tool which measures the existence and severity of symptoms of depression. Each of the 21 items on BDI-II tool represent a depressive symptom. Each symptoms were scored on a 4-point scale of 0 to 3 (0=symptom not present); (3=symptom very intense). Scores for each symptom were added up to obtain the total scores for all 21 items, which were interpreted as follows: Scores of 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression and 29-63: severe depression, where higher scores indicated more depression. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Beck Depression Inventory (BDI) Total Score at Weeks 26, 104, and 156 Week 104	2.00 score on a scale Standard Deviation 3.37
Change From Baseline in Beck Depression Inventory (BDI) Total Score at Weeks 26, 104, and 156 Week 156	-3.43 score on a scale Standard Deviation 7.09
Change From Baseline in Beck Depression Inventory (BDI) Total Score at Weeks 26, 104, and 156 Week 26	-0.89 score on a scale Standard Deviation 8.13

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

For each scheduled visit for this assessment, 3 timed overnight urine samples were collected between 4 to 7 days of each other. All urine samples were collected within a 16-day period. ACR and PCR were determined for each collection. The median of the values determined for the 3 collections/visit was used for analysis. Baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 ACR: Week 52	1.00 mg/g Standard Deviation 57.23
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 ACR: Week 26	-26.22 mg/g Standard Deviation 26.75
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 ACR: Week 104	12.21 mg/g Standard Deviation 71.82
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 ACR: Week 156	-1.14 mg/g Standard Deviation 54.80
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 PCR: Week 26	-38.33 mg/g Standard Deviation 24.40
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 PCR: Week 52	0.33 mg/g Standard Deviation 62.11
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 PCR: Week 104	-12.88 mg/g Standard Deviation 76.97
Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 PCR: Week 156	-34.38 mg/g Standard Deviation 71.40

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

The summary statistics of all continuous echocardiogram variables were calculated for each visit. The overall interpretation of the readings were summarized in 3 categories: normal, abnormal but not clinically significant (NCS), and abnormal but clinically significant (CS) categories. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Baseline · Abnormal CS	0 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 26 · Abnormal CS	0 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 104 · Abnormal NCS	3 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Baseline · Normal	6 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Baseline · Abnormal NCS	2 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 26 · Normal	6 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 26 · Abnormal NCS	3 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 52 · Normal	5 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 52 · Abnormal NCS	2 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 52 · Abnormal CS	0 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 104 · Normal	4 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 104 · Abnormal CS	0 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 156 · Normal	5 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 156 · Abnormal NCS	2 Participants
Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 Week 156 · Abnormal CS	0 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, and 156 post-ACT13739 baseline

All continuous MRI variables were summarized using descriptive statistics for each visit. The overall interpretation of the readings were summarized in 2 categories as: normal, and abnormal. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 Baseline · Normal	6 Participants
Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 Baseline · Abnormal	4 Participants
Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 Week 26 · Normal	7 Participants
Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 Week 26 · Abnormal	2 Participants
Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 Week 156 · Normal	4 Participants
Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 Week 156 · Abnormal	3 Participants

SECONDARY outcome

Timeframe: Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline

Estimated glomerular filtration rate was used to measure level of kidney function and determine the stage of kidney disease. Change from baseline in eGFR was obtained by subtracting baseline value from post-baseline value at Weeks 26, 52, 104 and 156. For this analysis, baseline was defined as initial ACT13739 study baseline.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=11 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 26, 52, 104, and 156 Week 26	-3.43 mL/min/1.73m^2 Standard Deviation 8.64
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 26, 52, 104, and 156 Week 52	-5.57 mL/min/1.73m^2 Standard Deviation 11.07
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 26, 52, 104, and 156 Week 104	-5.71 mL/min/1.73m^2 Standard Deviation 10.23
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 26, 52, 104, and 156 Week 156	-4.83 mL/min/1.73m^2 Standard Deviation 17.54

SECONDARY outcome

Timeframe: Weeks 52, 104, 156 and 160 (End of Treatment Follow-up) post-ACT13739 baseline

Population: Analysis population included participants in LTS14116 study with evaluable plasma Chit1 data. Only data collected during LTS14116 study were included in analysis. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Plasma concentrations of Chit1 over time were determined using mass spectrometry (MS)-based assay. For the analysis, 52 ng/mL was considered as the lower limit of quantification. Although identified in protocol as a secondary endpoint, plasma Chit1 is also an exploratory measure. Only LTS14116 timepoints were analyzed and are presented. Data summarized are the measured values at each time point (not change from baseline). Here, measured value '0.000' denotes no chitotriosidase detected in plasma for the 5 participants at Week 156 reported by laboratory for all evaluable participants.

Outcome measures

Outcome measures
Measure	GZ/SAR402671 n=7 Participants Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Chitotriosidase (Chit1) Plasma Concentration Levels at Weeks 52, 104,156 and 160 (End of Treatment Follow-up) Week 52	35.965 ng/mL Standard Deviation 46.520
Chitotriosidase (Chit1) Plasma Concentration Levels at Weeks 52, 104,156 and 160 (End of Treatment Follow-up) Week 104	12.785 ng/mL Standard Deviation 20.993
Chitotriosidase (Chit1) Plasma Concentration Levels at Weeks 52, 104,156 and 160 (End of Treatment Follow-up) Week 156	0.000 ng/mL Standard Deviation 0.000
Chitotriosidase (Chit1) Plasma Concentration Levels at Weeks 52, 104,156 and 160 (End of Treatment Follow-up) Week 160 (End of Treatment Follow-up)	6.483 ng/mL Standard Deviation 6.309

Adverse Events

GZ/SAR402671

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GZ/SAR402671 n=11 participants at risk Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Blood and lymphatic system disorders Haemolysis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Deafness unilateral	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Vertigo	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Floppy infant	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Ischaemic stroke	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Psychiatric disorders Depressed mood	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Psychiatric disorders Intentional self-injury	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.

Other adverse events

Other adverse events
Measure	GZ/SAR402671 n=11 participants at risk Participants received GZ/SAR402671 15 mg once daily orally for 36 months during combined ACT13739/LTS14116 treatment period.
Cardiac disorders Atrial fibrillation	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Cardiac disorders Atrioventricular block first degree	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Cardiac disorders Cardiomyopathy	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Cardiac disorders Sinus bradycardia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Deafness unilateral	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Ear pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Middle ear effusion	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Tinnitus	27.3% 3/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Ear and labyrinth disorders Vertigo	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Blepharitis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Chalazion	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Diplopia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Eye pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Lacrimation increased	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Lenticular opacities	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Retinal vascular disorder	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Eye disorders Vision blurred	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Abdominal pain upper	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Constipation	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Diarrhoea	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Dry mouth	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Gastrooesophageal reflux disease	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Nausea	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Oesophageal discomfort	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Toothache	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Gastrointestinal disorders Vomiting	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Fatigue	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Feeling hot	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Influenza like illness	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Non-cardiac chest pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Oedema	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Oedema peripheral	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Pain	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Pyrexia	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
General disorders Temperature intolerance	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Conjunctivitis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Ear infection	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Herpes simplex	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Influenza	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	36.4% 4/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Periodontitis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Pharyngitis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Pharyngitis streptococcal	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Rhinitis	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Upper respiratory tract infection	27.3% 3/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Infections and infestations Upper respiratory tract infection bacterial	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Arthropod bite	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Contusion	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Joint injury	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Limb injury	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Meniscus injury	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Muscle strain	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Tooth fracture	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Injury, poisoning and procedural complications Wound	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Investigations Electrocardiogram T wave abnormal	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Investigations Electrocardiogram abnormal	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Investigations Glomerular filtration rate decreased	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Investigations Nuclear magnetic resonance imaging brain abnormal	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Investigations Vibration test abnormal	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Metabolism and nutrition disorders Decreased appetite	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Arthralgia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Back pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Muscle twitching	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Myalgia	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Neck pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Amnesia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Balance disorder	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Burning sensation	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Carpal tunnel syndrome	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Cerebral ischaemia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Dizziness	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Headache	36.4% 4/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Hemiparesis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Hypoaesthesia	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Memory impairment	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Migraine	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Monoparesis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Neuralgia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Paraesthesia	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Presyncope	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders Tremor	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Nervous system disorders White matter lesion	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Psychiatric disorders Anxiety	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Psychiatric disorders Depressed mood	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Psychiatric disorders Depression	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Psychiatric disorders Nervousness	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Renal and urinary disorders Micturition frequency decreased	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Cough	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dry throat	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.2% 2/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Hiccups	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Sinus pain	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Acne	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Angiokeratoma	27.3% 3/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Dermatitis contact	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Hyperhidrosis	9.1% 1/11 • From baseline of ACT13739 study up to 37 months post-ACT13739 baseline. Reported AEs were TEAEs, defined as AEs that developed/worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurs first). Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

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.
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