A Phase 3b Single Arm Clinical Study to Evaluate the Efficacy and Safety of MT1621 in Nucleos(t)Ide Treatment Naïve Pediatric and Adolescent Subjects With Thymidine Kinase 2 (TK2) Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- Proportion of subjects acquiring a Motor Milestone
研究概览
简要总结
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study of the efficacy and safety of MT1621 in pediatric and adolescent patients with thymidine kinase 2 deficiency (TK2d). In order to be eligible for this study, participants must have genetic confirmation of TK2d and must not have ever received MT1621 or nucleos(t)ides before entering the study.
详细描述
Thymidine kinase 2 (TK2) is a protein involved in the normal function of mitochondria. Thymidine kinase 2 deficiency (TK2d) is a form of mitochondrial DNA depletion syndrome and is a very rare inherited genetic disorder. TK2d leads to abnormally low amounts of DNA in mitochondria and because of this defect, the mitochondria are not able to provide the energy that cells need to function properly, which causes severe muscle weakness, along with host of additional symptoms that may involve the respiration, feeding, and ambulation, and can progress until patients lose many of these abilities. There are no FDA-approved medicines to treat TK2d.
MT1621 is a therapy that targets the underlying pathophysiology of TK2d by restoring mitochondrial DNA (mtDNA) replication fidelity. MT1621 consists of a combination of deoxynucleosides (the building blocks of mtDNA) given orally. Deoxynucleoside combination therapy improves nucleotide balance, increases mtDNA copy number, improves cell function, and prolongs life in preclinical models of TK2d.
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study to assess the efficacy and safety of MT1621 in treatment naïve pediatric and adolescent subjects <18 years of age with TK2d. The study seeks to enroll approximately 16 subjects globally in this ultra rare disease.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be aged birth to <18 years of age on the day of consent.
- •Diagnosis of TK2 deficiency based on confirmed disease-causing mutation(s) in the TK2 gene.
- •Onset of TK2d at ≤12 years of age as defined as the age at which the first TK2d symptom occurred.
排除标准
- •Documented clinically significant central nervous system involvement.
- •ALT or AST >3 x upper limit of normal and total bilirubin > 2 x ULN or International Normalized Ratio (INR) >1.
- •EtCO2>45 mmHg if not on ventilatory support
- •Current or prior treatment with nucleos(t)ides for TK2d.
研究组 & 干预措施
Single Arm
Male and female Participants <18 years
干预措施: MT1621 (Drug)
结局指标
主要结局
Proportion of subjects acquiring a Motor Milestone
时间窗: 12 months
Proportion of subjects acquiring a motor milestone not present at baseline after 12 months of MT1621 treatment.
次要结局
- Time to Acquisition of a Motor Milestone(12 months)
- Survival(12 months)