A Phase I/II Study of Bucladesine in Patients with Severe Methylmalonic Acidemia

JRCT ID: jRCT2041210065

Registered date:04/09/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: methylmalonic acidemia
• Date of first enrollment: 10/03/2022
• Target sample size: 6
• Study type: Interventional
• Intervention(s): Bucladesine will be administered intravenously over 60 minutes once a week. Starting dose is 0.3mg/kg. PK and safety data will be evaluated. Then, dosage will be incerased to 0.55mg/kg and administered repeatedly with monitoring safety data.

Outcome(s)

• Primary Outcome: Suspected adverse reaction rate
• Secondary Outcome: Adverse event rate, Serious suspected adverse reaction rate, PK, Clinical response

Key inclusion & exclusion criteria

• Age minimum: >= 3month old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Diagnosis of methylmalonic acidemia (MMA) defined by biochemical diagnostic criteria on the MMA guideline 2019
(2) Developmental quotient (DQ) <= 75 on Kyoto scale of psychological development 2020, OR, Initial clinical presentation of MMA occured before the report of newborn tandem mass screening test result, OR, Abnormal metabolic lab result* on dietary and medical management
*Abnormal metablic lab reslut is defined as a situation where any of the following conditions applies.
i) High anion gap (>15mEq/L) metabolic acidosis, and pH<7.3, HCO3-<22mmol/L, or pCO2<35mmHg (respiratory compensation) (VBG)
ii) Hyperammonemia: blood ammonia level>80ug/dL
iii) Hyperlactacidemia: blood lactic acid level>22mg/dL
iv) Hypoglycemia: random blood glucose level<70mg/dL
(3) 3 months old or older at a time of starting the investigational drug
(4) Written informed consent obtained by a patient (or a parent/legal guardian of the patient if a patient is under the age of 20)

Exclude criteria

(1) Vitamin B12 responsive MMA
(2) History of liver or kidney transplant
(3) AST or ALT elevated more than 5 times the upper limit of normal
(4) Any serious diseases not related to MMA
(5) Gestatoinal age <37 weeks at birth: This does not apply if over 12 months old at the time consent is obtained.
(6) History of allergy to bucladesine
(7) History of acute myocardial infarction or cardiomyopathy
(8) History of arrhythmia
(9) Having diabetes
(10) Having any renal cyst, OR, Family history of polycystic kidney disease
(11) History of illicit drug or alcohol abuse
(12) Use of any investigational drug or device in other clinical studies within 30 days before obtaining an informed consent
(13) Pregnant or breast feeding women. Not following contraception requirement during the clinical study.
(14) Not eligible for this clinical study decided by an investigator or sub-investigator

Related Information

• Primary Sponsor: Ito Tetsuya
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)