A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of GM1 Gangliosidosis or GM2 Gangliosidosis

Azafaros

Status and phase

Enrolling

Phase 3

Conditions

Gangliosidosis, GM1

Gangliosidoses, GM2

Treatments

Drug: AZ-3102

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT07082543

2024-515778-28-00 (EU Trial (CTIS) Number)

AZA-001-301-GMx

Details and patient eligibility

About

An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of GM1 gangliosidosis or GM2 gangliosidosis

Full description

Please see NCT #07054515 for information on the AZA-001-301 Master Protocol

PRIMARY OBJECTIVE

The primary objective of this study is to demonstrate superior efficacy on ataxic manifestations with oral nizubaglustat dosing compared with placebo when administered over 18 months in participants with late-infantile and juvenile forms of GM1/GM2 gangliosidosis

SECONDARY OBJECTIVES

I. To assess additional efficacy in ataxic and non-ataxic manifestations comparing nizubaglustat dosing with placebo when administered over 18 months in participants with late-infantile and juvenile forms of GM1/GM2 gangliosidosis

II. To assess the pharmacokinetic (PK) properties of nizubaglustat after administration of the first dose (Visit 1) and at steady state after multiple once daily doses

III. To assess the pharmacodynamic (PD) effects of nizubaglustat

IV. To assess the safety and tolerability of daily oral nizubaglustat dosing compared with placebo, when administered over 18 months in participants with late-infantile and juvenile forms of GM1/GM2 gangliosidosis

Enrollment

75 estimated patients

Sex

All

Ages

4+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Confirmed GM1 gangliosidosis or Tay-Sachs, Sandhoff, or GM2AB variant
Male and female participants aged 4 years and older at the time of informed consent
Onset of neurological symptoms from 1 to 10 years
Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and ≤30 at Baseline
Females of childbearing potential who are sexually active willing to follow the contraceptive guidance
Male participants with a female partner of childbearing potential willing to follow the contraceptive guidance

Exclusion criteria

A history of medical conditions other than GM1 or GM2 gangliosidosis that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results
Body weight of <10 kg
The presence of another neurologic disease
The presence of moderate or severe hepatic impairment
The presence of moderate or severe renal impairment
Platelet count of <100x10^9/L
The dose of any anti-epileptic treatment(s) was not stable (required a change in dose within the previous 3 months) and/or a new anti-epileptic treatment (drug or procedure) was prescribed in the month before Baseline
Prior use of an investigational drug within the 3 months before Screening; or prior participation in a clinical study involving gene therapy or stem cell transplantation within 2 years prior to Screening
A positive serum pregnancy test (for women of childbearing potential)