NCT06181136进行中（未招募）1 期
A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 5
- 主要终点
- Change from baseline in the natural logarithm of cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
研究概览
简要总结
This is a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of DNL126 in participants with Sanfilippo syndrome Type A (MPS IIIA). The core study period is 25 weeks (approximately 6 months); followed by an open-label extension (OLE), which extends through Week 97 (approximately 18 months); and a long-term extension (LTE), which extends through Week 193 (Year 4). Participants with MPS IIIA will be enrolled in two planned cohorts, and additional participants with MPS IIIA may be enrolled in three optional cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of MPS IIIA
- •For Cohort A2: No more than 1 participant may have predictors of a slow-progressing phenotype
- •For Cohort A3: Approximately 2 participants will have predictors of the slow-progressing phenotype
- •For Cohort B1: Have a severe phenotype based on having at least one of the following:
- •An older sibling with the same genotype and severe MPS IIIA, in the opinion of the investigator
- •A definitive genotype indicative of severe MPS IIIA, in the opinion of the investigator
- •Clinical symptoms of MPS IIIA prior to 28 months of age that, in the opinion of the investigator, are indicative of severe MPS IIIA
- •For Cohort B2: Are an older sibling of a participant in Cohort B1 (who has already been confirmed to be eligible for dosing) with MPS IIIA, the same causative genotype, and who has severe MPS IIIA in the opinion of the investigator
排除标准
- •Have unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
- •Have lost the ability to walk independently, in the opinion of the investigator
- •Are unable to take the majority of nutrition via mouth, in the opinion of the investigator
- •For Cohort B only: Are homozygous or compound heterozygous for the N-sulfoglucosamine sulfohydrolase (SGSH) S298P mutation or any other mutation known to be associated with slow-progressing phenotype
- •Have used any CNS-targeted MPS IIIA enzyme replacement therapy (ERT) (eg, intrathecal SGSH or TfR-mediated SGSH delivery to CNS) within 3 months before Day 1
- •Have a prior history of hematopoietic stem cell transplantation
- •Have a prior history of gene therapy
- •Have used genistein or anakinra within 7 days of screening or intended use of genistein or anakinra during the study
- •Have a documented likely pathogenic mutation sufficient to cause disease (eg, taking into account zygosity) of other genes that are known to be associated with developmental delay, seizures, or other significant CNS disorders
- •Have clinically significant thrombocytopenia, other clinically significant coagulation abnormality, significant active bleeding, or require treatment with an anticoagulant or more than two antiplatelet agents
- •Contraindication for lumbar punctures
- •Contraindication for MRI scan
- •Have a clinically significant history of stroke, status epilepticus, head trauma with loss of consciousness, or any clinically significant CNS disease that is not MPS IIIA-related within 3 months of screening
- •Have had a ventriculoperitoneal (VP) shunt placed or a clinically significant VP shunt malfunction within 30 days of screening
- •Have any clinically significant CNS trauma or disorder, including severe untreated intracranial hypertension or brain surgery, that, in the opinion of the investigator, may interfere with assessment of study endpoints or make participation in the study unsafe
研究组 & 干预措施
Cohort A2
Experimental
Participants with MPS IIIA
干预措施: DNL126 (Drug)
Cohort A1
Experimental
Participants with MPS IIIA
干预措施: DNL126 (Drug)
Cohort A3
Experimental
Participants with MPS IIIA
干预措施: DNL126 (Drug)
Cohort B1
Experimental
Participants with MPS IIIA
干预措施: DNL126 (Drug)
Cohort B2
Experimental
Participants with MPS IIIA
干预措施: DNL126 (Drug)
结局指标
主要结局
Change from baseline in the natural logarithm of cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
时间窗: 49 weeks
Percentage change from baseline in cerebrospinal fluid (CSF) concentration of heparan sulfate (HS)
时间窗: 49 weeks
次要结局
- Change from baseline in the natural logarithm of urine HS (normalized to creatinine) concentration(49 weeks)
- Change from baseline in liver volume multiples of normal(49 weeks)
- Change from baseline in the natural logarithm of serum neurofilament light chain (NfL) concentration(73 weeks)
- Percentage change from baseline in urine concentration of HS (normalized to creatinine)(49 weeks)
- Change from baseline in liver volume(49 weeks)
- Percentage change from baseline in serum neurofilament light chain (NfL) concentration(73 weeks)
- Participants with CSF HS concentration within the normal range(49 weeks)
研究者
研究点 (5)
Loading locations...
相似试验
尚未招募
1 期
A Study of CM313 in Subjects With Relapsed or Refractory Multiple MyelomaMultiple MyelomaNCT06126237Keymed Biosciences Co.Ltd120
进行中（未招募）
1 期
A Study YL201 in Patients With Selected Advanced Solid TumorsAdvanced Solid TumorNCT06057922MediLink Therapeutics (Suzhou) Co., Ltd.990
进行中（未招募）
1 期
Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell MalignanciesPhase I: Relapsed or Refractory B-cell MalignanciesPhase II Cohort A: Relapsed or Refractory Mantle Cell LymphomaPhase II Cohort B: Relapsed or Refractory Chronic Lymphocytic LeukemiaNCT03932331AstraZeneca105
撤回
1 期
NTLA-3001 in Adults with Alpha-1 Antitrypsin Deficiency-Associated Lung DiseaseLung DiseasePulmonary DiseaseAlpha-1 Antitrypsin Deficiency-associated Lung DiseaseAATDAlpha-1 Antitrypsin DeficiencyNCT06622668Intellia Therapeutics30
招募中
2 期
A Study of HB0025 Injection in Patients With Advanced Renal CancerRenal CancerNCT06222125Huabo Biopharm Co., Ltd.100