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An Open-Label, Dose Escalation, Proof-of-Concept Clinical Trial of Chaperone therapy of Neuronopathic Gaucher Disease with Ambroxol (Chaperone therapy of Neuronopathic Gaucher Disease with Ambroxol)

Chaperone therapy of Neuronopathic Gaucher Disease with Ambroxol (Chaperone therapy of Neuronopathic Gaucher Disease with Ambroxol)

22

The number of informed consent acquisition were 22 subjects in this study, and all 22 subjects were enrolled and administered the study drug. In this study, all 22 subjects enrolled was recruited in Safety Analysis Set and Full Analysis Set.

This study was conducted in multi-hospital. First enrollment was achieved in March 16, 2010, and last subject was enrolled in October 20, 2015. Fifteen subjects completed the study, and 7 subjects discontinued from the study (3 for adverse event, 3 for insufficient effect and 1 for withdrawal of concent).

In this study, all 22 subjects enrolled was recruited in Safety Analysis Set, and none of them were excluded from the analysis. Adverse events (AEs) occurred in 19 subjects, with an incidence of 86.4% (19/22 subjects). Serious adverse events (SAEs) occurred in 7 subjects, with an incidence of 31.8% (7/22 subjects). AEs with a causal relationship to the study drug (ADR) occurred in 7 subjects, and the incidence was 31.8% (7/22 subjects). No serious ADR was observed. Discontinuation due to AEs were reported in 3 subjects, and 1 of them discontinued due to ADR (drug hypersensitivity).

The primary endpoints were adverse events (AEs) and vital signs, electrocardiogram, and abnormal changes in laboratory test values. A summary of AEs, regardless of causality, is provided in the Adverse Events module. No significant changes in various laboratory test values and drug-induced long QT syndrome were observed. Exploratory endpoints included a significant increase in lymphocyte GBA activity and a significant decrease in cerebrospinal fluid glucosylsphingosine concentration. There were no clinically significant changes in hemoglobin, platelet count and hepatosplenomegaly compared to baseline, but there was a significant decrease in ACE levels. In neurological symptoms, a decrease in UMRS score and improvement in pupillary function were observed.

A long term and high dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte GBA activity and decreased glucosylsphingosine levels in the cerebrospinal fluid. Various neurological symptoms were improved. The results of this study had been confirmed the clinical efficacy of this drug in patients with neuronopathic Gaucher disease.

Mar. 31, 2024

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs061180090

Maegaki Yoshihiro

Tottori University Hospital

36-1 Nishi-cho, Yonago, Tottori, Japan

maegaki@med.tottori-u.ac.jp

Narita Aya

Tottori University Hospital

36-1 Nishi-cho, Yonago, Tottori, Japan

+81-859-38-6777

aya.luce@nifty.com

Complete

Feb. 10, 2010

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

1)Patients with neuronopathic Gaucher disease, defined by the presence of deficiency of glucocerebrosidase activities in lymphocytes/fibroblasts and 2 mutated GBA alleles.
2)Patients with known sequence variants associated with ABX effectiveness (such as F213I,N188S,R120W,G202R), or prior known positive result on in-vitro chaperone test using ABX.
3)Signed written informed consent

1) Current participation in another investigational study, or using other investigational drug within 3 months prior to the participation to the trial.
2) Patients who are not appropriate to participate to the trial.

Both

Neuronopathic Gaucher disease

Ambroxol at a dose level of 25 mg/kg/day (upper limit: 1300mg/day) will be given by mouth for 6 months.

Gaucher disease, Pharmacological chaperone therapy, ambroxol

D005776

Primary Outcome Measures: Safety
Safety will be based on physical exam, vital signs, adverse event query, and clinical pathology (includes chemistry, hematology and urinalysis), asessed at baseline and approximately biweekly during the study.

Secondary Outcome Measures: Efficacy
Efficacy is based on biomarker (glucocerebrosidase activities in lymphocytes), changes in neurological or neurophysiological assessments, activities of daily
living (ADLs).

+81-859-38-7021

Jan. 29, 2019

none