Trial · NCT04221451

A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2

NCT04221451, Phase 3, Terminated, Genzyme, a Sanofi Company; results first posted 2026-01-28

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2. Trials, record NCT04221451. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04221451

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT number: NCT04221451
Status: Terminated
Phases: Phase 3
Enrollment: 75 participants, actual
Lead sponsor: Genzyme, a Sanofi Company
Conditions: Tay-Sachs Disease, Sandhoff Disease
Interventions: venglustat GZ402671, placebo
First posted: 2020-01-09
Last updated: 2026-01-28
Other registries' IDs: eudract:2019-002375-34
Results first posted: 2026-01-28
Limitations and caveats: The study was early terminated based on the absence of positive trends on clinical endpoints; there were no safety concerns. For sialidosis type 1 and juvenile/adult galactosialidosis, due to the rarity of the disease and the specificity of the endpoint, reporting individual-level data would risk compromising participant privacy and confidentiality.

Source ClinicalTrials.gov

Registered outcomes19

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	PAP: PP: Percent Change From Baseline in CSF GM2 Biomarker to Week 104	Baseline (Day 1) and Week 104	Lumbar puncture was performed for obtaining CSF samples at specified timepoints to assess the presence of GM2 biomarker in PP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP.
Primary	PAP: PP: Annualized Rate of Change From Baseline in the 9-HPT to Week 104	Baseline (Day 1) and Week 104	9-HPT is a test of upper extremity (arm and hand) function.Participant is seated at table with small, shallow container holding pegs and block containing 9 empty holes.On start command when stopwatch is started,participant picks up 9 pegs one at a time as quickly as possible, puts them in 9 holes and once they are in holes, removes them again as quickly as possible one at a time,replacing them into shallow container. Both dominant and non-dominant hands are tested twice (2 consecutive trials of dominant hand followed immediately by 2 consecutive trials of non-dominant hand).Total time (ranging up to 300 seconds):averaged, converted to reciprocals which were averaged and back-transformed to obtain global 9-HPT.Higher value on 9-HPT is indicative of higher disability.Mean annualized rate of change in 9-HPT was obtained from exponential transformation of mean slope of log-transformed 9-HPT.Baseline: last available value before or equal to the first dose of study drug date in the PAP.
Primary	PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants	Baseline (Day 1) and Week 104	Plasma and CSF samples were collected at specified timepoints to assess the presence of GL-1 and GM2 biomarkers in juvenile/adolescent late-onset GM2 gangliosidosis participants of SP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP.
Primary	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 and GM1 Biomarkers to Week 104 in GM1 Gangliosidosis Participants	Baseline (Day 1) and Week 104	Plasma and CSF samples were collected at specified timepoints to assess the presence of GL-1 and GM1 biomarkers in GM1 gangliosidosis participants of SP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP.
Primary	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM2 and Monosialodihexosylganglioside (GM3) Biomarkers to Week 104 in Sialidosis Type 1 Participant	Baseline (Day 1) and Week 104	Plasma and CSF samples were collected at specified timepoints to assess the presence of GL-1, GM2 and GM3 biomarkers in sialidosis type 1 participant of SP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP. Analysis was planned to be performed on sialidosis type 1 participant from secondary PD population (all enrolled participants with this clinical diagnosis who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD).
Primary	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM1 and GM3 Biomarkers to Week 104 in Juvenile/Adult Galactosialidosis Participants	Baseline (Day 1) and Week 104	Plasma and CSF samples were collected at specified timepoints to assess the presence of GL-1, GM1 and GM3 biomarkers in juvenile/adult galactosialidosis participants of SP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP. Analysis was planned to be performed on juvenile/adult galactosialidosis participant from secondary PD population which included all enrolled participants with this clinical diagnosis who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD.
Primary	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 Biomarker to Week 104 in Saposin C Deficiency Participants	Baseline (Day 1) to Week 104	Plasma and CSF samples were planned to be collected at specified timepoints to assess the presence of GL-1 biomarkers in saposin C deficiency participants of SP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP.
Secondary	PAP: PP: Absolute Change From Baseline in CSF GM2 Biomarker to Week 104	Baseline (Day 1) and Week 104	Lumbar puncture was performed for obtaining CSF samples at specified timepoints to assess the presence of GM2 biomarker in PP in PAP. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP.
Secondary	PAP: PP and SP: Change From Baseline in 25-foot Walk Test (25FWT) to Week 104	Baseline (Day 1) and Week 104	The 25FWT is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly and safely as possible for 2 trials (can use assistive devices). The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The amount of time (in seconds) to walk 25 feet is recorded (ranging up to 180 seconds). The 25FWT score is defined as the average of 2 trials. A higher value on the 25FWT is indicative of higher disability. The baseline value was defined as the last available value before or equal to the first dose of study drug date in the PAP.
Secondary	PAP: PP and SP: Change From Baseline in the Neurological Examination of the Friedreich's Ataxia Rating Scale (FARS) (FARS-neuro) to Week 104	Baseline (Day 1) and Week 104	The FARS-neuro includes 23 items and is composed of 4 sections that assesses different neurological faculties: bulbar activity (4 items), upper limb coordination (5 items assessed right and left side), lower limb coordination (2 items assessed right and left side), peripheral nervous system (5 items assessed right and left side) and upright stability (7 items). Total score is calculated as the sum of scores on items of this section and ranges from 0 to 117; mean is presented. Higher value indicates higher disability. Baseline=last available value before or equal to first dose of study drug date in PAP. PP: primary efficacy population: all randomized participants with diagnosis of late-onset GM2 gangliosidosis aged \>=18 years. SP: secondary efficacy population: all enrolled participants with diagnosis of juvenile/adolescent late-onset GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1, or juvenile/adult galactosialidosis.

1 to 10 of 19Source ClinicalTrials.gov

See all 19 registered outcomes

Outcomes19

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	PAP: PP: Percent Change From Baseline in CSF GM2 Biomarker to Week 104	Baseline (Day 1) and Week 104	PAP: Primary PD population included all randomized participants with diagnosis of late-onset GM2 gangliosidosis aged \>=18 years who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD. Only those participants with data collected at specified timepoints are reported.	percent change	MEAN
PRIMARY	PAP: PP: Annualized Rate of Change From Baseline in the 9-HPT to Week 104	Baseline (Day 1) and Week 104	PAP: Primary efficacy population included all randomized participants with diagnosis of late-onset GM2 gangliosidosis aged \>=18 years. Only those participants with data collected at specified timepoints are reported.	percent per year	MEAN
PRIMARY	PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants	Baseline (Day 1) and Week 104	PAP: Analysis was performed on juvenile/adolescent late-onset GM2 gangliosidosis participants from secondary PD population which included all enrolled participants with this clinical diagnosis who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD.	percent change	MEAN
PRIMARY	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 and GM1 Biomarkers to Week 104 in GM1 Gangliosidosis Participants	Baseline (Day 1) and Week 104	PAP: Analysis was performed on GM1 gangliosidosis participants from secondary PD population which included all enrolled participants with this clinical diagnosis who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD. Only those participants with data collected at specified timepoints are reported.	percent change	MEAN
PRIMARY	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM2 and Monosialodihexosylganglioside (GM3) Biomarkers to Week 104 in Sialidosis Type 1 Participant	Baseline (Day 1) and Week 104	Due to the rarity of the disease and the specificity of the endpoint, reporting individual-level data would risk compromising participant privacy and confidentiality. As presented in baseline characteristics, only 1 participant with sialidosis type 1 was enrolled in the study.	percent change	MEAN
PRIMARY	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM1 and GM3 Biomarkers to Week 104 in Juvenile/Adult Galactosialidosis Participants	Baseline (Day 1) and Week 104	Due to the rarity of the disease and the specificity of the endpoint, reporting individual-level data would risk compromising participant privacy and confidentiality. As presented in baseline characteristics, only 1 participant with juvenile/adult galactosialidosis was enrolled in the study.	percent change	MEAN
PRIMARY	PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 Biomarker to Week 104 in Saposin C Deficiency Participants	Baseline (Day 1) to Week 104	PAP: Analysis was planned to be performed on saposin C deficiency participants from secondary PD population which included all enrolled participants with this clinical diagnosis who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD. As presented in baseline characteristics, there was no participant enrolled with Saposin C deficiency.
SECONDARY	PAP: PP: Absolute Change From Baseline in CSF GM2 Biomarker to Week 104	Baseline (Day 1) and Week 104	PAP: Primary PD population included all randomized participants with diagnosis of late-onset GM2 gangliosidosis aged \>=18 years who received at least 1 dose of study drug and who had baseline and post-baseline assessments of PD. Only those participants with data collected at specified timepoints are reported.	ng/mL	MEAN
SECONDARY	PAP: PP and SP: Change From Baseline in 25-foot Walk Test (25FWT) to Week 104	Baseline (Day 1) and Week 104	PAP PP:primary efficacy population included all randomized participants with diagnosis of late-onset GM2 gangliosidosis aged \>=18 years.PAP SP: secondary efficacy population included all enrolled participants with a clinical diagnosis of juvenile/adolescent late-onset GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1, or juvenile/adult galactosialidosis.Only those participants with ability to walk at baseline and data collected at specified timepoints are reported.	seconds	MEAN
SECONDARY	PAP: PP and SP: Change From Baseline in the Neurological Examination of the Friedreich's Ataxia Rating Scale (FARS) (FARS-neuro) to Week 104	Baseline (Day 1) and Week 104	Only those participants with data collected at specified timepoints are reported. For sialidosis type 1: due to the rarity of the disease and the specificity of the endpoint, reporting individual-level data would risk compromising participant privacy and confidentiality. As presented in baseline characteristics, only 1 participant with sialidosis type 1 was enrolled in the study.	score on a scale	MEAN

1 to 10 of 19Source ClinicalTrials.gov

See all 19 outcomes

Results by group96

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
PAP: PP: Percent Change From Baseline in CSF GM2 Biomarker to Week 104	PAP: PP: Placebo		-11.33	Standard Error 4.23	percent change
PAP: PP: Percent Change From Baseline in CSF GM2 Biomarker to Week 104	PAP: PP: Venglustat		-47.57	Standard Error 3.04	percent change
PAP: PP: Annualized Rate of Change From Baseline in the 9-HPT to Week 104	PAP: PP: Placebo		0.95	Standard Error 1.92	percent per year
PAP: PP: Annualized Rate of Change From Baseline in the 9-HPT to Week 104	PAP: PP: Venglustat		2.49	Standard Error 1.35	percent per year
PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants	PAP: SP: Venglustat	GL-1: CSF	-82.35	Standard Deviation 9.94	percent change
PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants	PAP: SP: Venglustat	GL-1: Plasma	-79.28	Standard Deviation 2.56	percent change
PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants	PAP: SP: Venglustat	GM2: CSF	-43.41	Standard Deviation 23.14	percent change
PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants	PAP: SP: Venglustat	GM2: Plasma	-55.91	Standard Deviation 11.76	percent change
PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 and GM1 Biomarkers to Week 104 in GM1 Gangliosidosis Participants	PAP: SP: Venglustat	GL-1: CSF	17.42	Standard Deviation 188.41	percent change
PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 and GM1 Biomarkers to Week 104 in GM1 Gangliosidosis Participants	PAP: SP: Venglustat	GL-1: Plasma	-80.42	Standard Deviation 8.17	percent change

1 to 10 of 96Source ClinicalTrials.gov

See all 96 results by group

Participant flow36

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
PAP: Baseline (Day 1) up to 104 Weeks	STARTED	PAP: PP: Placebo	19
PAP: Baseline (Day 1) up to 104 Weeks	STARTED	PAP: PP: Venglustat	40
PAP: Baseline (Day 1) up to 104 Weeks	STARTED	PAP: SP: Venglustat	16
PAP: Baseline (Day 1) up to 104 Weeks	STARTED	OLE: PP: Delayed Venglustat	0
PAP: Baseline (Day 1) up to 104 Weeks	STARTED	OLE: PP: Early Venglustat	0
PAP: Baseline (Day 1) up to 104 Weeks	STARTED	OLE: SP: Venglustat	0
PAP: Baseline (Day 1) up to 104 Weeks	COMPLETED	PAP: PP: Placebo	17
PAP: Baseline (Day 1) up to 104 Weeks	COMPLETED	PAP: PP: Venglustat	35
PAP: Baseline (Day 1) up to 104 Weeks	COMPLETED	PAP: SP: Venglustat	14
PAP: Baseline (Day 1) up to 104 Weeks	COMPLETED	OLE: PP: Delayed Venglustat	0

1 to 10 of 36Source ClinicalTrials.gov

See all 36 participant flow

Adverse events1,152

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Bacterial Infection	Infections and infestations	PAP: PP: Placebo	0	19	0
other	Bacterial Infection	Infections and infestations	PAP: PP: Venglustat	0	40	0
other	Bacterial Infection	Infections and infestations	PAP: SP: Venglustat	1	16	1
other	Bacterial Infection	Infections and infestations	OLE: PP: Delayed Venglustat	0	16	0
other	Bacterial Infection	Infections and infestations	OLE: PP: Early Venglustat	0	34	0
other	Bacterial Infection	Infections and infestations	OLE: SP: Venglustat	0	14	0
other	Bacterial Vaginosis	Infections and infestations	PAP: PP: Placebo	0	19	0
other	Bacterial Vaginosis	Infections and infestations	PAP: PP: Venglustat	0	40	0
other	Bacterial Vaginosis	Infections and infestations	PAP: SP: Venglustat	0	16	0
other	Bacterial Vaginosis	Infections and infestations	OLE: PP: Delayed Venglustat	0	16	0

1 to 10 of 1,152Source ClinicalTrials.gov

See all 1,152 adverse events

Adverse event totals18

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	PAP: PP: Placebo	0	19
Total, all-cause mortality	PAP: PP: Venglustat	0	40
Total, all-cause mortality	PAP: SP: Venglustat	1	16
Total, all-cause mortality	OLE: PP: Delayed Venglustat	1	16
Total, all-cause mortality	OLE: PP: Early Venglustat	0	34
Total, all-cause mortality	OLE: SP: Venglustat	0	14
Total, other adverse events	PAP: PP: Placebo	19	19
Total, other adverse events	PAP: PP: Venglustat	38	40
Total, other adverse events	PAP: SP: Venglustat	14	16
Total, other adverse events	OLE: PP: Delayed Venglustat	11	16

1 to 10 of 18Source ClinicalTrials.gov

See all 18 adverse event totals

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
34539759	DERIVED

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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