A Study to Evaluate the Effects and Safety of Hydroxocobalamin in Participants With Combined Methylmalonic Academia (cblC Type)

Официальное название

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)

Обзор

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).

Вмешательства

• Препарат Hydroxocobalamin Chloride Injection
  1 - 20 mg per dose, 1 - 5 times per week

Первичные конечные точки

• Proportion of participants achieving normalization of plasma or urinary methylmalonic acid levels post-dose. [Срок оценки: Week4、Week6、Week10、Week16、Week24]

Вторичные конечные точки (11)

• Change from baseline in plasma total homocysteine level. [Срок оценки: 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. [Срок оценки: Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48]
• Change from baseline in plasma methylmalonic acid concentration. [Срок оценки: Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48]
• Change from baseline in urinary methylmalonic acid excretion. [Срок оценки: Day3、Week2、Week4、Week6、Week10、Week16、Week24、Week32、Week40、Week48]
• Proportion of participants achieving plasma methylmalonic acid levels within the normal reference range. [Срок оценки: Week32、Week40、Week48]
• Proportion of participants achieving urinary methylmalonic acid levels within the normal reference range. [Срок оценки: Week32、Week40、Week48]
• Change from baseline in growth parameters (height). [Срок оценки: Week24、Week48]
• Change from baseline in growth parameters (weight) [Срок оценки: Week24、Week48]
• Change from baseline in growth parameters (head circumference). [Срок оценки: Week24、Week48]
• Change from baseline in Gesell Developmental Scales. [Срок оценки: Week24、Week48]
• Change from baseline in Wechsler Intelligence Scale [Срок оценки: Week24、Week48]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07163364 · SYH9097-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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