A Phase 2 Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With Thymidine Kinase 2 Deficiency (TK2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 9
- 主要终点
- Safety as adverse events (AEs): number of participants who experience adverse events
研究概览
简要总结
This is a Phase 2 prospective open-label treatment study of the safety and efficacy of doxecitine and doxribtimine in study participants with thymidine kinase 2 (TK2) deficiency who participated in the retrospective study MT-1621-101 [NCT03701568] or who were receiving nucleos(t)ide treatment and were approved by the Sponsor.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by the parent(s) or legally authorized representative (LAR) and/or assent by the study participant (when applicable).
- •Confirmed genetic mutation in the TK2 gene.
- •Absence of other genetic disease or polygenic disease.
- •Current treatment with nucleos(t)ides for TK2 deficiency. Study participants who were not previously enrolled in MT-1621-101 [NCT03701568] will require Sponsor approval to ensure that collection of clinical and functional measurements prior to treatment are sufficient to serve as baseline assessments for purposes of evaluating safety and efficacy.
- •Female study participants must not be breastfeeding, have a negative pregnancy test at screening (females ≥10 years old), and have no intention to become pregnant during the course of the study. Female study participants who are of childbearing potential (ie, following menarche until ≥1 year post-menopausal if not anatomically and physiologically incapable of becoming pregnant) must agree and commit to the use of highly effective methods of birth control for the duration of the study and for 30 days after the end of the study. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (ie, <1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method. In certain countries (if permitted by law), women of childbearing potential may instead agree to abide by heterosexual sexual abstinence during the study and for 30 days after the end of the study.
- •Male study participants with sexual partners should use condoms for the duration of the study and for 30 days after the last dose of study drug to prevent passing study drug to the partner in the ejaculate. Male participants should be advised not to donate sperm for 30 days after the last dose of study drug.
- •Willingness to maintain current treatment regimen and current exercise regimen for the duration of the clinical study.
- •Willingness to comply with the study protocol, including but not limited to, all study procedures, study visits, and study drug compliance.
排除标准
- •History of liver disease, or liver function test results (ALT, AST, or total bilirubin) ≥2× upper limit of normal without prior Sponsor approval.
- •Other significant medical condition that, in the opinion of the Investigator or Study Sponsor, may confound interpretation of the clinical course of TK2 deficiency.
研究组 & 干预措施
doxecitine and doxribtimine
This is an open label study with all participants in a single arm. Study participants will take doxecitine and doxribtimine up to a maximum of 800 mg/kg/day (400 mg/kg/day doxecitine and 400 mg/kg/day doxiribtimine).
干预措施: doxecitine and doxribtimine (Drug)
结局指标
主要结局
Safety as adverse events (AEs): number of participants who experience adverse events
时间窗: Approximately 3 years
Safety as determined by the number of participants who experience adverse events (AE), type of AE, severity of AE.
Safety as determined by laboratory measurements
时间窗: Approximately 3 years
Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests.
Safety as determined by electrocardiograms (ECGs)
时间窗: Approximately 3 years
Number of Participants Who Experience a Clinically Significant Change from Baseline ECG.
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: From first administration of study drug until end of safety follow-up (up to approximately 7 years)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.
Incidence of TEAEs leading to study drug withdrawal
时间窗: From first administration of study drug until end of safety follow-up (up to approximately 7 years)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.
次要结局
- Time to maximum plasma concentration (Tmax) of deoxycytidine and deoxythymidine(Approximately 3 years)
- Biomarkers (plasma from blood)(Approximately 3 years)
- Efficacy - Motor Function Assessments(Approximately 3 years)
- Efficacy - Respiratory Status(Approximately 3 years)
- Apparent elimination half-life (t1/2) of deoxycytidine and deoxythymidine(Approximately 3 years)
- Quality of life through patient questionnaire - Individualized Neuromuscular Quality of Life (INQoL)(Approximately 3 years)
- Maximum plasma concentration (Cmax) of deoxycytidine and deoxythymidine(Approximately 3 years)
- Efficacy Assessment: Clinical Global Impression of Improvement (CGI-I) and Patient Global Impression of Improvement (PGI-I)(Approximately 3 years)
- Efficacy - Growth/Nutrition(Approximately 3 years)
- AUC - area under the plasma concentration time curve of deoxycytidine and deoxythymidine(Approximately 3 years)
- Characterization of health care utilization(Approximately 3 years)
- Clinical Global Impression of Improvement (CGI-I) Response score(Assessed at end of study (approximately 7 years))
- Mean minimum plasma concentration (Cmin) of deoxycytidine (dC) and deoxythymidine (dT) at steady state(Plasma samples will be collected at Months 1, 3, and 6)
- Mean maximum plasma concentration (Cmax) of dC and dT at steady state(Plasma samples will be collected at Months 1, 3, and 6)
- Mean area under the plasma concentration - time curve from time 0 to 24 hours (AUC0-24) of dC and dT at steady state(Plasma samples will be collected at Months 1, 3, and 6)