a multi-cohort study of safety, efficacy, pk and pd of gnr-055 in patients with mucopolysaccharidosis type ii

Conditions: Mucopolysaccharidosis Type II; Metabolic Diseases

Summary: this is phase 2/3 study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational product gnr-055 in mps ii (hunter syndrome) patients of different age groups.

gnr-055 is intended for ert in patient with mucopolysaccharidosis type ii (mps ii), or hunter syndrome. mps ii is a recessive x-linked inheritance lysosomal storage disease, which is characterized by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (id2s), caused by a mutation in the id2s gene. enzyme deficiency leads to the accumulation of glycosaminoglycans (gag) (mainly of heparan and dermatan sulfates) in lysosomes of almost all types of cells of various tissues and organs. the disease is manifested by growth retardation, damage of many organs and systems, severe deformations of bones and joints, gross facial features, pathology of the respiratory and cardiovascular systems, damage to parenchymal organs (hepatosplenomegaly), and hearing impairment. a severe form of the disease occurs with the involvement of the nervous system in the pathological process, including mental retardation, behavior anomalies, and impaired motor function. gnr-055 is a recombinant modified id2s capable to penetrate the blood-brain barrier and thus expected to prevent neurodegenerative consequences and the cognitive deficit and to attain a significant improvement in the life quality and expectancy of patients with mps ii. study idb-mps-ii-iii is a multicenter, open-label, multi-cohort study to assess safety, pk and pd, and efficacy of gnr-055 in patients of different age groups with mps ii (hunter syndrome).

Eligibility criteria:
inclusion criteria: * signed inform consent; * verified diagnosis of mps ii (hunter syndrome); * naïve patients or patients who have received standard ert whit idursulfase products; * no contraindications for lumbar puncture as judged by the investigator; * willingness and ability to follow study procedures. exclusion criteria: * clinically pronounced hypersensitivity to id2s or any other component of the drug product; * history of hematopoietic stem cell transplantation (hsct) or bone marrow transplantation; * implanted or external non-removable metal devices, a cardiac pacemaker, or other objects sensitive to the magnetic field that may pose a danger to both the wearer and the correct operation of magnetic resonance imaging (mri) equipment; * concomitant diseases and conditions that, in the investigator's opinion, can put at risk the patient's safety during his/her participation in the study, or which will influence the safety data analysis in case of the disease/condition exacerbation during the study.

Keywords: mucopolysaccharidosis type ii cognitive dysfunction metabolic diseases lysosomal storage diseases neurocognitive disorders metabolism, inborn genetic diseases, inborn neurobehavioral manifestations neurologic manifestations genetic diseases, x-linked hunter syndrome iduronate-2-sulfatase modified i2s protein connective tissue diseases mental disorders intellectual disability nervous system diseases heredodegenerative disorders, nervous system cognition disorders mental retardation, x-linked