Pilot Study of TTI-0102 in Cystinosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 6
- 主要终点
- White blood cell (WBC) cystine
研究概览
简要总结
White blood cell (WBC) cystine levels serve as the primary therapeutic target for monitoring cysteamine treatment in cystinosis, with a goal of <1.9 nmol ½ cystine/mg protein as measured 5-6 hours post-dose when treated with immediate-release formulation, Cystagon® , or 11-12 hours post-dose when treated with delayed-release formulation, Procysbi®, using UCSD granulocyte assay.
Although cysteamine dosing in cystinosis has traditionally been individualized based on WBC cystine levels, the FDA-approved Cystagon® prescribing information now includes an approximate recommended maintenance dose of 1.30 g/m²/day. When this dosing strategy is plotted against body weight, it aligns with the dosing regimen of TTI-0102 that was found effective in mitochondrial diseases, demonstrating a linear relationship between dose and weight.
The main objective of this study is to demonstrate that administration of a single dose of 60 ± 5 mg/kg/day of TTI-0102 (~26 mg/kg cysteamine base equivalent) allows maintenance of WBC cystine at <1.9 nmol ½ cystine/mg protein over 24 hours as determined by UCSD granulocyte assay.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-65 years with a confirmed diagnosis of cystinosis based on clinical features and/or genetic testing, with or without history of kidney transplantation.
- •Currently treated with a stable dose of Cystagon® or Procysbi® for at least 3 months prior to enrollment.
- •Body weight between 50 kg and 80 kg at screening.
- •Able to attend all required study visits and comply with study procedures, including blood draws over a 24-hour period.
- •Able to provide informed consent in English.
- •The first 3 patients must have WBC cystine levels over the last year no more than 50% greater than the upper limit of target level
排除标准
- •Known hypersensitivity or allergy to cysteamine, pantetheine, TTI-0102, or any excipients in the study drug.
- •Clinically significant uncontrolled medical conditions (e.g., unstable cardiac, hepatic, or renal disease) that, in the investigator's judgment, would increase risk or interfere with study participation.
- •Participation in another interventional clinical trial within 30 days prior to screening.
- •Any condition that, in the investigator's opinion, would make the participant an unsuitable candidate (e.g., inability to comply with procedures, significant cognitive impairment, active substance use disorder).
- •Any patient who is pregnant, plans to become pregnant or is unwilling to use contraceptive measures during study participation.
研究组 & 干预措施
TTI-0102 (cysteamine-pantetheine disulfide)
Given once daily for 7 days
干预措施: TTI-0102 (cysteamine-pantetheine disulfide) (Drug)
结局指标
主要结局
White blood cell (WBC) cystine
时间窗: Comparison of baseline, Day 1-2, Day 3-4, and treatment end (Day 7)
The primary endpoint is the change in white blood cell (WBC) cystine levels following treatment with TTI-0102. The study will evaluate whether a weight-based dose of 60 ± 5 mg/kg/day maintains WBC cystine levels below 1 nmol ½ cystine/mg protein over 24 hours.
次要结局
- Pharmacodynamic biomarker: tryptophan in plasma(Baseline (Day 0) to treatment end (Day 7))
- Pharmacokinetic parameter: Cmax(At specified days/timepoints during the treatment period: Day1-2, Day 3-4, Day 7)
- Pharmacokinetic parameter: Tmax(At specified days/timepoints during the treatment period: Day1-2, Day 3-4, Day 7)
- Pharmacokinetic parameter: AUC(At specified days/timepoints during the treatment period: Day1-2, Day 3-4, Day 7)
- Pharmacodynamic biomarker: lactate in plasma(Baseline (Day 0) to treatment end (Day 7))
- Pharmacodynamic biomarker: pyruvate in whole blood(Baseline (Day 0) to treatment end (Day 7))