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Phase II study of galactosidase as therapy for type IV galactosemia

Study of galactosidase as therapy for type IV galactosemia

3

The first individual was a 5-year-old boy who had cataracts until the age of 2 years, without other complications, and was assigned to Group A. The second individual was a 7-year-old girl with no complications and was assigned to Group B. The third candidate was a 2-year-old boy assigned to Group A, but he was excluded from the study due to papilledema at the ophthalmological screening. The third individual was a 5-year-old boy with no complications was assigned to Group B.

The planned number of cases was 8, but due to the COVID-19 pandemic, additional enrollment could not be expected. A request for early discontinuation of this study was submitted, and the Efficacy and Safety Evaluation Committee met and recommended early discontinuation of the study. Therefore, this study was stopped early at the completion of the implementation of the study in three cases.

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The blood galactose levels at 2 or 3 hours after lactose loading as planned primary outcome were not significant different between the group with and without galactosidase (2 hours after lactose loading, the mean blood galactose levels in galactosidase-free group was 18.2 mg/dL, the levels in galactosidase-treated group was 9.7 mg/dL, p = 0.08, and 3 hours after lactose loading, the levels in in galactosidase-free group was 4.5 mg/dL, the levels in galactosidase-treated group was 4.0 mg/dL, p = 0.22). However, as an unexpected fact, the peak of blood galactose in the group with galactosidase was delayed compared with that in the group without galactosidase, and the comparison of blood galactose at certain time was not appropriate. Thus, the most plausible outcome seems to be the peak value of blood galactose, and the peak levels of blood galactose was significantly decreased by the administration of the galactosidase (the mean blood galactose peak level in galactosidase-free group was 31.2 mg/dL, the level in galactosidase-treated group was 22.2 mg/dL, p=0.0046). The result indicated the clinical efficacy of the galactosidase in type IV galactosemia.

This study demonstrated that the galactosidase treatment for type IV galactosemia can reduce blood galactose levels in lactose loading, suggesting the galactosidase may be a therapeutic agent for type IV galactosemia.

Mar. 31, 2023

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https://jrct.mhlw.go.jp/latest-detail/jRCTs021200008

Kure Shigeo

Tohoku University Hospital

1-1 Seiryomachi, Aobaku, Sendai, Miyagi

kure@med.tohoku.ac.jp

Wada Yoichi

Tohoku University Hospital

1-1 Seiryomachi, Aobaku, Sendai, Miyagi

+81-22-717-7287

wada@med.tohoku.ac.jp

Complete

Mar. 01, 2020

Interventional

randomized controlled trial

open(masking not used)

no treatment control/standard of care control

crossover assignment

treatment purpose

Patients are diagnosed to type IV galactosemia by genetic test (pathogenic variants in GALM gene are identified by exome or direct sequencing) or GALM enzyme activity test.

(1) Patients with severe liver disease or liver injury (AST, ALT > 1.25 x upper limits of normal)
(2) Patients have participated to other clinical study or trial
(3) Patients with constipation which is in need of treat
(4) Patients with psychological problem

Both

type IV galactosemia

Test twice per patient will be performed using crossover technique.
group A: (lactose and galactosidase loading) , followed by (lactose loading)
group B: (lactose loading) , followed by (lactose and galactosidase loading)
Dose of lactose and galactosidase are 1.0 g/kg and 0.05 g/kg, respectively.
Eight cases are devided to group A or B.

galactosemia: galactose mutarotase: GALM

D005693

Blood galactose levels at 2 or 3 hours after lactose loading

Difference between peak level of blood galactose and minimum level of blood galactose after 30 minutes after lactose loading
Peak level of blood galactose
Peak level of urine galactitol

+81-22-718-0461

April. 27, 2020

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