GM2 Gangliosidosis, Niemann-Pick Type C Disease
Conditions
Keywords
Nizubaglustat
Brief summary
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).
Detailed description
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.
Interventions
DRUGAZ-3102
Daily oral intake of AZ-3102 dispersible tablets
Sponsors
Azafaros B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohort 1 (NPC and GM2 patients): * Have been randomized into Phase 2 Study AZA-001-5A2-01. OR Cohort 2 (NPC patients): * Be male or female aged ≥12 years * Have a genetically-confirmed diagnosis of NPC disease * Have received full-dose Miglustat treatment for at least 12 months and experienced disease stabilization or worsening with treatment over the 2 previous clinic visits. Patients experiencing clinical improvement with Miglustat over the preceding 3 months should not be considered for this study. * Wish to change treatment to Nizubaglustat for their NPC disease. * Participants from Phase 2 Study AZA-001-5A2-01 (RAINBOW) who transitioned to Miglustat may be eligible for Cohort 2 if they meet all other criteria. Participation is supported and deemed beneficial by the Principal Investigator. Be willing and able to be evaluated for all protocol assessments. The participant, parent, and/or legal guardian can read, understand, and sign the informed consent form. Where appropriate, assent will also be sought for participants who have not reached the age of majority.
Exclusion criteria
* A positive serum pregnancy test (only tested for women of childbearing potential). * Female planning to breastfeed during the study. * Any medical event/condition that prevents participation in the study based on the judgment of the Principal Investigator. * Participation in another interventional or non-interventional study or early access program.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in treatment-emergent adverse events (TEAEs) | Through study completion, an average of 4 years | Incidence and severity of all Adverse Events related to study drug treatment, study discontinuation or death |
| Change from baseline in electrocardiogram (ECG) | Through study completion, an average of 4 years | ECG read out Normal, Abnormal, Not Clinically Significant, Abnormal, Clinically Significant and Not Done. |
| Change from baseline in seizures | Through study completion, an average of 4 years | Seizure duration (minutes) as per the seizure diary. |
| Maximum observed plasma concentration (Cmax) | Baseline , Month 1 (Cohort 2 only) and Month 6 | — |
| Time to Cmax (Tmax) | Baseline, Month 1 (Cohort 2 only) and Month 6 | — |
| Concentration at trough (Ctrough) | 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 | Baseline, Month 1 (Cohort 2 only) and Month 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in the concentrations of Glucosylceramide (GlcCer) C16:0; C18:0 | Baseline, Month 1 (Cohort 2 only) and Month 6 |
| Change from Baseline in the concentrations of Neurofilament light chain (NfL) | Through study completion, an average of 4 years |
| For GM2 gangliosidosis patients: Change from Baseline in the concentrations of Monosialoganglioside GM2 (GM2) | Through study completion, an average of 4 years |
| For GM2 gangliosidosis patients: Change from Baseline in the concentrations of Lyso-monosialoganglioside GM2 | 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) | Through study completion, an average of 4 years |
Countries
Brazil
Outcome results
None listed