This open-label study aims to gather long-term safety, tolerability, PK, biomarker, and clinical efficacy data relating to daily administration of Nizubaglustat in participants previously enrolled in the Phase 2 RAINBOW study (Cohort 1). In addition, the study aims to assess safety, clinical, and biochemical impact of transitioning NPC disease patients to Nizubaglustat after prior treatment with stable, full-dose Miglustat (Cohort 2).
This is a multicenter, open-label study to assess the safety, tolerability, PK, PD, and efficacy of Nizubaglustat in male or female patients with late-infantile or juvenile onset GM2 gangliosidosis or NPC disease in two cohorts: * Cohort 1: Patients who previously took part in Phase 2 Study AZA-001-5A2-01 (RAINBOW) and wish to continue in this open-label study * Cohort 2: Approximately 10 patients with NPC disease, aged ≥12 years who received full-dose Miglustat for more than 12 months, have stable or worsening disease over the 2 previous clinic visits, and who wish to stop Miglustat treatment and transition to Nizubaglustat.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Daily oral intake of AZ-3102 dispersible tablets
Associação Hospitalar de Prot à Infância Dr. Raul Carneiro
Água Verde, Curitiba, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira
Rio de Janeiro, Brazil
Change from baseline in treatment-emergent adverse events (TEAEs)
Incidence and severity of all Adverse Events related to study drug treatment, study discontinuation or death
Time frame: Through study completion, an average of 4 years
Change from baseline in electrocardiogram (ECG)
ECG read out Normal, Abnormal, Not Clinically Significant, Abnormal, Clinically Significant and Not Done.
Time frame: Through study completion, an average of 4 years
Change from baseline in seizures
Seizure duration (minutes) as per the seizure diary.
Time frame: Through study completion, an average of 4 years
Change from baseline in seizures
Seizure frequency (number) as per seizure diary.
Time frame: Through study completion, an average of 4 years
Maximum observed plasma concentration (Cmax)
Time frame: Baseline , Month 1 (Cohort 2 only) and Month 6
Time to Cmax (Tmax)
Time frame: Baseline, Month 1 (Cohort 2 only) and Month 6
Concentration at trough (Ctrough)
Time frame: Baseline, Month 1 (Cohort 2 only) and Month 6
Area under the plasma concentration-time curve from the time of dosing (zero) to 24 hours post-dose
Time frame: Baseline, Month 1 (Cohort 2 only) and Month 6
Change from Baseline in the concentrations of Glucosylceramide (GlcCer) C16:0; C18:0
Time frame: Baseline, Month 1 (Cohort 2 only) and Month 6
Change from Baseline in the concentrations of Neurofilament light chain (NfL)
Time frame: Through study completion, an average of 4 years
For GM2 gangliosidosis patients: Change from Baseline in the concentrations of Monosialoganglioside GM2 (GM2)
Time frame: Through study completion, an average of 4 years
For GM2 gangliosidosis patients: Change from Baseline in the concentrations of Lyso-monosialoganglioside GM2
Time frame: Through study completion, an average of 4 years
For NPC disease patients: Change from Baseline in the concentrations of N-palmitoyl-O-phosphocholine-serine (PPCS)
Time frame: Through study completion, an average of 4 years
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