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

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To assess the long-term safety of GZ/SAR402671 in adult male participants with Fabry disease who previously completed study ACT13739 (NCT02489344). Secondary Objective: To assess the long-term effect of GZ/SAR402671 on pharmacodynamic and exploratory efficacy endpoints in adult male participants with Fabry disease who previously completed study ACT13739.

Detailed Description
-----------------
The total duration of this extension study (LTS14116) was up to 31 months (30 months of treatment and one month post-treatment follow-up).

Official Title
-----------------
An Open-label, Multicenter, Multinational Extension Study of the Long-term Safety, Pharmacodynamics, and Exploratory Efficacy of GZ/SAR402671 in Adult Male Patients Diagnosed With Fabry Disease

Conditions
-----------------
Fabry Disease

Intervention / Treatment
-----------------
* Drug: GZ/SAR402671


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Male participant with Fabry disease who previously completed study ACT13739. Participants, willing and able to provide signed informed consent. Sexually active participants, willing to practice true abstinence in line with their preferred and usual lifestyle or using two acceptable effective methods of contraception. Exclusion criteria : -Participants, in the opinion of the Investigator, unable to adhere to the requirements of the study. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GZ/SAR402671<br>Participants received GZ/SAR402671 15 milligrams (mg) once daily orally for 30 months in this extension study (LTS14116). | Drug: GZ/SAR402671<br>* Pharmaceutical form:capsule Route of administration: oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters | 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). | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Urinalysis | Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0 | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 
| Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities | 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. | From baseline of ACT13739 study up to 37 months post-ACT13739 baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso GL-3) Concentration at Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration At Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Plasma Monosialodihexosylganglioside (GM3) Concentration At Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Urine GL-3 Concentration At Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in High Sensitivity Cardiac Troponin T At Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Podocyturia Counts (Per Milligram of Creatinine) At Weeks 12, 26, and 156 | 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. | Baseline of ACT13739 study and Weeks 12, 26, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 | 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 pain in past 10 days (before each of the specified time points). Participants answered the question: Do you currently suffer from abdominal (tummy) pain? [Yes/No]. For this analysis, baseline was defined as initial ACT13739 study. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, and 156 post-ACT13739 baseline | 
| 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 | 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 responded to question How often do you eat less during meals due to abdominal pain and/or bloating? in past 10 days (before each of the specified time points) in the categories as 'never', 'occasionally' or 'often'. For this analysis, baseline was defined as initial ACT13739 study baseline. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| 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 | 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. | Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline | 
| Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Beck Depression Inventory (BDI) Total Score at Weeks 26, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 104, and 156 post-ACT13739 baseline | 
| Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, and 156 post-ACT13739 baseline | 
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 26, 52, 104, and 156 | 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. | Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline | 
| Chitotriosidase (Chit1) Plasma Concentration Levels at Weeks 52, 104,156 and 160 (End of Treatment Follow-up) | 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. | Weeks 52, 104, 156 and 160 (End of Treatment Follow-up) post-ACT13739 baseline |