A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II

study id #: NCT05208281

condition: Mucopolysaccharidosis Type II, Metabolic Diseases

status: Recruiting

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.

intervention: GNR-055 1.0-2.0-3.0 mg/kg, GNR-055 2.0 mg/kg, GNR-055 3.0 mg/kg

results: https://clinicaltrials.gov/ct2/show/results/NCT05208281

last updated: February 26, 2022

start date: November 30, 2021

estimated completion: March 2025

last updated: January 26, 2022

phase of development: Phase 2/Phase 3

size / enrollment: 32

study description: 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).

primary outcomes:

• Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
  Safety assessment will be performed based on the subjective complaints, physical examination, assessment of vital signs, laboratory tests, and 12-lead ECG; Incidence of allergic and infusion-related reactions; Incidence of Anti-Drug Antibodies (ADAs) against GNR-055 and their neutralizing activity.
• Baseline to Week 56
  Urine GAG excretion
  Changes in levels of urine GAG excretion after multiple-dose administration of GNR-055
• Baseline to Week 4, 8, 10, 26, and 52
  

secondary outcomes:

• Serum concentration of the GNR-055
  Week 52
• GAG level in CerebroSpinal Fluid (CSF)
  Baseline to Week 6, 10, 26, and 52
• Serum GAG level
  Baseline to Week 4, 8, 10, 26, and 52
• Large joint range of motion
  Week 8, 10, 26, and 52
• Liver and spleen volumes (MRI)
  Baseline to Week 8, 10, 26, and 52
• 6-minute walk test
  Baseline to Week 8, 10, 26, and 52
• Left ventricular mass by EchoCG
  Baseline to Week 8, 10, 26, and 52
• Lung Forced Vital Capacity (FVC)
  Baseline to Week 8, Week 26, and Week 52
• Neurocognitive functions assessment
  Baseline to Week 12, 26, and 52
• Brain white/gray matter structures (MRI)
  Baseline to Week 26, and 52
• Serum neuromarkers
  Baseline to Week 24, and 52
• CSF neuromarkers
  Baseline to Week 24, and 52

inclusion criteria:

exclusion criteria: 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.

sponsor: AO GENERIUM

contacts: Svetlana B. Korotkova, MD, PhD, +7(495) 988 47 94, sbkorotkova@generium.ru

investigators: Oksana A. Markova, MD, MSc,AO GENERIUM

trial center locations: Russian Federation

• Russian Federation
  Federal State Budgetary Educational Institution of Higher Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of the Russian Federation
  
  
• Russian Federation
  Federal State-Funded Healthcare Institution Central Clinical Hospital of the Russian Academy of Sciences (Research Institute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences)
  
  
• Russian Federation
  State Autonomous Healthcare Institution of the Sverdlovsk Region Regional Children’s Clinical Hospital
  
  
• Russian Federation
  State Budgetary Healthcare Institution Republican Medical Genetic Center
  
  
• Russian Federation
  V.I. Vernadsky Crimean Federal University