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

Inclusion criteria

• 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.

Exclusion criteria

• 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.