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

NCT02489344 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: LTS141162014-004995-49U1111-1165-9049
• Study Type: interventional
• Target: 8
• Locations: 5 countries
• Sites: 7

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.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (29)

• Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156

  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

  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

  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

  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

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

Study Arms (1)

GZ/SAR402671

EXPERIMENTAL

Participants received GZ/SAR402671 15 milligrams (mg) once daily orally for 30 months in this extension study (LTS14116).

Drug: GZ/SAR402671

Interventions

GZ/SAR402671 DRUG

Pharmaceutical form:capsule Route of administration: oral

GZ/SAR402671

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (7)

Investigational Site Number 840002

Atlanta, Georgia, 30322, United States

Location

Investigational Site Number 840003

Cincinnati, Ohio, 45229, United States

Location

Investigational Site Number 840001

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number 250001

Garches, 92380, France

Location

Investigational Site Number 616001

Warsaw, 04-730, Poland

Location

Investigational Site Number 643002

Moscow, 125167, Russia

Location

Investigational Site Number 826002

Cambridge, CB2 OQQ, United Kingdom

Location

Related Publications (1)

• Deegan PB, Goker-Alpan O, Geberhiwot T, Hopkin RJ, Lukina E, Tylki-Szymanska A, Zaher A, Sensinger C, Gaemers SJM, Modur V, Thurberg BL, Sharma J, Najafian B, Mauer M, DasMahapatra P, Wilcox WR, Germain DP. Venglustat, an orally administered glucosylceramide synthase inhibitor: Assessment over 3 years in adult males with classic Fabry disease in an open-label phase 2 study and its extension study. Mol Genet Metab. 2023 Feb;138(2):106963. doi: 10.1016/j.ymgme.2022.11.002. Epub 2022 Nov 9.

  PMID: 36481125 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

venglustat

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 3, 2015
• Study Start: July 7, 2015
• Primary Completion: November 20, 2018
• Study Completion: November 20, 2018
• Last Updated: March 23, 2021
• Results First Posted: December 9, 2019

Record last verified: 2021-02

Locations

FR (1); PL (1); RU (1); GB (1); US (3)