NCT07163364尚未招募3 期
A Single-arm Phase III Clinical Study to Evaluate the Efficacy and Safety of Hydroxocobalamin Chloride Injection in Participants With Methylmalonic Acidemia (MMA) With Elevated Homocysteine (Cobalamin C Deficiency)
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.0 个研究点目标入组 20 人开始时间: 2025年8月31日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 主要终点
- Proportion of participants achieving normalization of plasma or urinary methylmalonic acid levels post-dose.
研究概览
简要总结
This study is a Single-Center, Single-Arm, open-label, Phase III clinical study to evaluate the efficacy, safety characteristics of Hydroxocobalamin Chloride Injection (20 mg/mL) for Maintenance Therapy in participants with Methylmalonic Acidemia (MMA) with Elevated Homocysteine (Cobalamin C Deficiency).
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
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6 months (inclusive) to < 18 years at the time of first investigational product administration; both sexes eligible.
- •Confirmed diagnosis of cobalamin C (cbl C)-type methylmalonic acidemia (MMA) fulfilling ALL of the following:
- •Documented vitamin B12 responsiveness: ≥ 50 % reduction from pre-treatment baseline in plasma C3/C2 ratio and urinary methylmalonic acid following vitamin B12 therapy.
- •Presence of pathogenic MMACHC gene variants in a participant with MMA associated with hyperhomocysteinemia.
- •Investigator-assessed clinical stability, defined as:
- •No emergency room visits or hospitalizations within 6 months prior to screening for metabolic crises (e.g., electrolyte disturbances, metabolic acidosis, dysglycaemia, multi-organ failure); AND
- •Plasma methylmalonic acid within the normal reference range at screening.
- •Continuous treatment with injectable hydroxocobalamin for ≥ 3 months immediately preceding first dose of study drug.
- •Written informed consent obtained from participant and/or legally authorised representative; willingness and ability to comply with all study visits and procedures.
- •Female participants of childbearing potential (post-menarche) must have a negative serum β-hCG test at screening. All participants of reproductive potential (post-menarche females or males with documented spermarche) must use a highly effective contraceptive method throughout the study and for an appropriate post-study period as defined by local regulations.
排除标准
- •Use of any vitamin B12 preparation other than injectable hydroxocobalamin within 3 months prior to screening.
- •Participation in another clinical trial within 28 days or 5 half-lives of the investigational agent (whichever is longer) before screening initiation, except for screening-only participants who did not receive study drug.
- •Prior liver or kidney transplantation, or any prior cell-based therapy.
- •Any of the following laboratory abnormalities:
- •Hemoglobin < 90 g/L; or
- •Platelet count < 100 × 10⁹/L; or
- •Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²; or
- •Requirement for dialysis due to renal disease.
- •Evidence of clinically significant hepatic dysfunction defined as:
- •Alanine aminotransferase (ALT) > 2.0 × upper limit of normal (ULN);
- •Aspartate aminotransferase (AST) > 2.0 × ULN or total bilirubin > 1.5 × ULN;
- •Prothrombin time > 1.5 × ULN.
- •Hyperammonemia characterised by blood ammonia ≥ 3 × ULN, or any acute metabolic decompensation (e.g., lethargy, restlessness, somnolence, feeding refusal, or vomiting).
- •Evidence on prior imaging of a space-occupying lesion suspicious for malignancy, or any known history of malignancy.
- •New York Heart Association (NYHA) Class III or IV heart failure, or moderate-to-severe pulmonary hypertension.
- •Clinically significant urolithiasis identified on imaging performed during screening.
- •Presence of any of the following underlying conditions: immunodeficiency, severe malnutrition, congenital heart disease, congenital malformations of the respiratory system, or any clinically significant cardiac, hepatic, pulmonary, or renal disorder; diabetes mellitus; severe hematological disease; uncontrolled epilepsy or other significant central nervous system disorders.
- •History of severe hypersensitivity or known hypersensitivity/intolerance to hydroxocobalamin, structurally related compounds, or any excipients in the investigational product.
- •Any other condition or circumstance that, in the judgment of the investigator, would compromise participant safety, compliance, or data integrity.
研究组 & 干预措施
Hydroxocobalamin Chloride Injection
Experimental
Hydroxocobalamin Chloride Injection
干预措施: Hydroxocobalamin Chloride Injection (Drug)
结局指标
主要结局
Proportion of participants achieving normalization of plasma or urinary methylmalonic acid levels post-dose.
时间窗: Week4、Week6、Week10、Week16、Week24
次要结局
- Change from baseline in plasma total homocysteine level.(Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48)
- Change from baseline in plasma propionylcarnitine (C3), plasma C3/acetylcarnitine (C2) ratio, and urinary methylcitrate.(Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48)
- Change from baseline in plasma methylmalonic acid concentration.(Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48)
- Change from baseline in urinary methylmalonic acid excretion.(Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48)
- Proportion of participants achieving plasma methylmalonic acid levels within the normal reference range.(Week32、Week40、Week48)
- Proportion of participants achieving urinary methylmalonic acid levels within the normal reference range.(Week32、Week40、Week48)
- Change from baseline in growth parameters (height).(Week24、Week48)
- Change from baseline in growth parameters (weight)(Week24、Week48)
- Change from baseline in growth parameters (head circumference).(Week24、Week48)
- Change from baseline in Gesell Developmental Scales.(Week24、Week48)
- Change from baseline in Wechsler Intelligence Scale(Week24、Week48)
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