Launch of an investigator-initiated trial of VGN-R08b for treating type II Gaucher disease (GDII)


The 1st in-human trial of VGN-R08b, a gene therapy product independently developed by Shanghai Vitalgen BioPharma Co., Ltd. (hereinafter referred to as "Vitalgen"), has been initiated in collaboration with Xinhua Hospital, affiliated with the Shanghai JiaoTong University School of Medicine.  This trial will evaluate the tolerability, safety and efficacy of intracerebroventricular administration of VGN-R08b for treating GDII patients.  

Director Zhang Huiwen, an expert on pediatric endocrine and genetic metabolic diseases from Xinhua Hospital and the principal investigator of the study project, presided over the initiation meeting, and Shen Wei, director of the Office under Drug Clinical Trial Institution, Wang Xiaoqiang, deputy director of Pediatric Neurosurgery, Zhu Yueniu, deputy director of Department of Pediatric Critical Medicine, He Dake, director of Pediatric Neurology, together with other investigators, the sponsor and SMO attended the meeting.

At the initiation meeting, the Clinical Development Department of Vitalgen gave an overall overview of the study background, study protocol and the study procedures of this particular project. At the meeting, director Zhang Huiwen said: “ type II Gaucher disease, also known as neural Gaucher disease, is usually developed at young ages characterized by fast onset and high mortality. Currently, no effective therapies have been available for this disease, therefore, highly unmet clinical needs for effective treatment can be found among the patients. The conduct of this very study project will undoubtedly deliver promising prospects for patients with Gaucher disease, and we are delighted to carry out active work on developing this potential new therapy together with Vitalgen as a clinical trial facility.”

Image: Initiation meeting for the early clinical study on VGN-R08b injection in the treatment of type II Gaucher disea

“An exploratory clinical study to evaluate the tolerability and safety of VGN-R08b by intracerebroventricular injection in patients with type II Gaucher disease” is a clinical study on an AAV-mediated gene therapy product. The study is now recruiting patient volunteers nationwide and consultation from patients and their family members are sincerely expected at Xinhua Hospital.

Intended subjects

1.  Infants aged within 24 months;

2.  Patients with medical records showing diagnosis of Gaucher disease as confirmed by GCase activity testing, and with a double allele mutation in GBA1;

3.  Patients showing neurological signs or symptoms consistent with that of type II Gaucher disease;

4.  The parents or guardians of the subject are able to fully understand the study information, purpose of the study and the risks involved as described in the Informed Consent Form (ICF), give their authorization for the use of the subject's health information and provide the properly signed and dated ICF ;

5.  The parents or guardians of the subject are willing to participate in the study as information providers to provide relevant information on the subject's health status, cognitive competence and physical functions (including providing information for use in grading scales to be used in the study).

Contact information

Contact doctor: Zhang Huiwen

Contact address Department of Pediatric Endocrinology and Genetic Metabolic Diseases, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

About Gaucher disease
Gaucher disease (GD) is an autosomal recessive metabolic disorder, in which the activity of glucocerebrosidase (GCase) in the lysosomes within the human body is decreased due to the mutation occurred in glucocerebrosidase gene (GBA1), thus causing its substrate of glucocerebroside (also known as glucosylceramide) to be stored in the lysosomes of macrophages in organs and parts such as the liver, spleen, bone, lung, brain, eyes and form "Gaucher cells", which often manifests as signs like hepatosplenomegaly, ostalgia, anemia, thrombocytopenia, and neurologic symptoms, and other manifestations due to affected systems may also be observed, and are likely to aggravate on a progressive basis in the course of the disease development. GD can be classified into three types based on the involvement of the nervous system and the rate at which the disease progresses: (1) Type I GD, non neuropathic and the most common type, showing no signs of primary central nervous system involvement; (2) Type II GD, acute neuropathic type with extensive and severe viceral involvement, showing onset within one year after birth and causing most deaths within two years after birth; (3) Type III GD, chronic neuropathic type with its incidence higher than that of type II GD, mostly seen in children with slow disease progression.
Type II GD is classified as an acute neuropathic type and is characterized by significant signs of “early onset, high severity and rapidly progressive degeneration in the brain stem”. Type II GD can be observed in the early infancy and often shows severe visceral diseases and certain neurological signs; and most patients died from rapid progression of relevant neurological signs within two years after birth. The enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) currently available are treatments specially developed for non-neurological symptoms of Gaucher disease. However, these therapies will not achieve therapeutic effects on neurological symptoms due to the inaccessibility of drugs used in these therapies into the brain of the patients.

About VGN-R08b
As a gene therapy product independently developed by Vitalgen, VGN-R08b is an adeno-associated virus (AAV)-based gene replacement therapy specially developed for the treatment of Type II Gaucher disease (GD) for single-dose administration. When delivered to the central nervous system by intracerebroventricular (ICV) injection, VGN-R08b will transduce neurons and glial cells in which the functional GCase protein is expressed. The GCase protein derived from VGN-R08b will be translocated to lysosomes to restore GCase activity, after which the pathologically accumulated sphingolipid glucose ceramide GC will be decomposed into glucose and ceramide in the patient's brain. VGN-R08b will also be transduced into peripheral organs such as liver and spleen with the use of an extensive promoter, thus making it possible for patients to achieve peripheral benefits at the same time.

About the Department of Pediatric Endocrinology and Genetics, Xinhua Hospital

Established in 1981, the specialty of pediatric endocrinology and pediatric genetic diseases in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine is one of the key specialties under the “Pediatrics” in the National "211" Project of Shanghai Jiaotong University School of Medicine and a key specialty under the “Pediatrics” of Shanghai Municipal Education Commission; it is also a Research Base for Genetic Metabolic Diseases under Shanghai Municipal Education Commission, a Prenatal Diagnosis Center in Shanghai, a Screening Center for Neonatal Diseases in Shanghai and a deputy leader unit of the Chinese Society of Pediatric Endocrinology and Metabolism.
In terms of endocrinology, it has carried out extensive studies on the diagnosis, treatment of various endocrine diseases such as dwarfism caused by growth hormone deficiency, sexual precocity, obesity, thyroid disease, adrenal gland diseases and pituitary gland diseases. In terms of genetic metabolic disease, it was the first to conduct neonatal screening in 1981 and successfully calculated the incidence of phenylketonuria (PKU) and congenital hypothyroidism (CH) in China. Furthermore, it has additionally set up screening for diseases such as congenital adrenal hyperplasia (CAH), glucose-6-phosphate dehydrogenase deficiency (G6PD), and galactosemia, and established an integrated functional service system integrating neonatal screening, diagnosis, prenatal diagnosis, treatment, and popularization of phenylketonuria.

About Vitalgen
Founded in March 2020 in Shanghai, China, Vitalgen is committed to converting the cutting-edge genetic and cellular therapeutic technologies into clinically feasible and accessible therapies to generate curative benefits for more patients.
Vitalgen has fully established the ViVec®AAV vector screening platform, ViLNP® lipid nanoparticle technology platform, ViCas®CRISPR gene editing technology platform and ViHiYi®AAV high-yield technology platform with independent intellectual property rights. With the proper use of strategies such as gene replacement, gene regulation and gene editing, it specializes in developing innovative gene therapy drugs for the treatment of central nervous system diseases, metabolic and hematological system diseases, ophthalmic diseases and tumors, and has set up diversified pipelines including multiple potential First-in-class products.
As of now, Vitalgen has successfully received multiple round of investment from well-known funds such as IDG, Loyal Valley Capital, Hillhouse Capital, and Jifeng Ventures etc..; it has set up a gene therapy R&D operation center with an area of 2,500 m2 and a gene therapy pilot production workshop with an area of 3,000 m2 in Zhangjiang High-tech Park and Lingang New Area respectively; in addition, it has another GMP-compliant workshop for commercial production under vigorous planning and construction.