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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 3
- 主要终点
- Change from baseline in treatment-emergent adverse events (TEAEs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cohort 1 (NPC and GM2 patients):
- •Have been randomized into Phase 2 Study AZA-001-5A2-
- •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.
排除标准
- •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.
研究组 & 干预措施
All patients
Arms (both cohorts 1 and 2): Nizubaglustat (AZ-3102)
干预措施: AZ-3102 (Drug)
结局指标
主要结局
Change from baseline in treatment-emergent adverse events (TEAEs)
时间窗: 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)
时间窗: 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
时间窗: Through study completion, an average of 4 years
Seizure duration (minutes) as per the seizure diary.
Maximum observed plasma concentration (Cmax)
时间窗: Baseline , Month 1 (Cohort 2 only) and Month 6
Time to Cmax (Tmax)
时间窗: Baseline, Month 1 (Cohort 2 only) and Month 6
Concentration at trough (Ctrough)
时间窗: 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
时间窗: Baseline, Month 1 (Cohort 2 only) and Month 6
次要结局
- 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)