A Study to Evaluate the Safety and Efficacy of Nizubaglustat (AZ-3102) in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease

Official title

Open-label Study to Evaluate the Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Nizubaglustat (AZ-3102) in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease, With or Without Previous Administration of Miglustat

Overview

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

• Drug AZ-3102
  Daily oral intake of AZ-3102 dispersible tablets

Primary outcome measures

• Change from baseline in treatment-emergent adverse events (TEAEs) [Time frame: Through study completion, an average of 4 years]
• Change from baseline in electrocardiogram (ECG) [Time frame: Through study completion, an average of 4 years]
• Change from baseline in seizures [Time frame: Through study completion, an average of 4 years]
• Change from baseline in seizures [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]

Secondary outcome measures (5)

• 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 3 centers

• Associação Hospitalar de Prot à Infância Dr. Raul Carneiro — Água Verde
• Hospital de Clinicas de Porto Alegre — Porto Alegre
• Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira — Rio de Janeiro

Identifiers

NCT: NCT07399704 · AZA-001-5A2-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗