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

Multicenter, Open-Label, Multi-cohort Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Drug Product GNR 055 (JSC "GENERIUM", Russia) in Patients With Mucopolysaccharidosis Type II

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.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Diseases; Mucopolysaccharidosis Type II
• Intervention / Treatment: Drug: GNR-055 1.0-2.0-3.0 mg/kg; Drug: GNR-055 2.0 mg/kg; Drug: GNR-055 3.0 mg/kg

Detailed 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).

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Svetlana B. Korotkova, MD, PhD; Phone Number: 7096 +7(495) 988 47 94; Email: sbkorotkova@generium.ru
• Study Contact Backup: Name: Oksana A. Markova, MD, MSc; Phone Number: 7077 +7(495) 988 47 94; Email: oamarkova@generium.ru

Study Locations

• Russian Federation
  • Ekaterinburg, Russian Federation, 620149
    • Recruiting
    • State Autonomous Healthcare Institution of the Sverdlovsk Region Regional Children's Clinical Hospital
  • Moscow, Russian Federation, 119333
    • Not yet recruiting
    • 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)
  • Simferopol, Russian Federation, 295007
    • Recruiting
    • V.I. Vernadsky Crimean Federal University
  • St. Petersburg, Russian Federation, 194100
    • Not yet recruiting
    • Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State Pediatric Medical University" of the Ministry of Health of the Russian Federation
  • Ufa, Russian Federation, 450076
    • Recruiting
    • State Budgetary Healthcare Institution Republican Medical Genetic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult: GNR-055; GNR-055: 1.0-2.0-3.0 mg/kg	Drug: GNR-055 1.0-2.0-3.0 mg/kg; Weekly IV infusion (lyophilized powder) 1.0-2.0-3.0 mg/kg; Other Names: GNR-055
Experimental: Paediatric: GNR-055 2.0 mg/kg; GNR-055 2.0 mg/kg	Drug: GNR-055 2.0 mg/kg; Weekly IV infusion (lyophilized powder) 2.0 mg/kg; Other Names: GNR-055
Experimental: Paediatric: GNR-055 3.0 mg/kg; GNR-055 3.0 mg/kg	Drug: GNR-055 3.0 mg/kg; Weekly IV infusion (lyophilized powder) 3.0 mg/kg; Other Names: GNR-055

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of the GNR-055	Assessment of the serum concentration of GNR-055 and calculation of Cmax, AUC, T1/2, Cl et other parameters after multiple-dose administration	Week 52
GAG level in CerebroSpinal Fluid (CSF)	Changes in levels of CSF GAG after multiple-dose administration of GNR-055	Baseline to Week 6, 10, 26, and 52
Serum GAG level	Changes in levels of serum GAG after multiple-dose administration of GNR-055	Baseline to Week 4, 8, 10, 26, and 52
Large joint range of motion	Changes over time in the large joint range of motion after multiple-dose administration of GNR-055	Week 8, 10, 26, and 52
Liver and spleen volumes (MRI)	Changes over time in liver and spleen volume according to ultrasound/MRI after multiple-dose administration of GNR-055	Baseline to Week 8, 10, 26, and 52
6-minute walk test	Changes over time in the results of the 6-minute walk test after multiple-dose administration of GNR-055	Baseline to Week 8, 10, 26, and 52
Left ventricular mass by EchoCG	Changes over time in the left ventricular mass according to Echocardiography (Echo-CG) after multiple-dose administration of GNR-055	Baseline to Week 8, 10, 26, and 52
Lung Forced Vital Capacity (FVC)	Changes over time in FVC according to spirometry after multiple-dose administration of GNR-055	Baseline to Week 8, Week 26, and Week 52
Neurocognitive functions assessment	Changes over time in neurocognitive functions after multiple-dose administration of GNR-055	Baseline to Week 12, 26, and 52
Brain white/gray matter structures (MRI)	Changes over time in the quantitative MRI brain structure parameters after multiple-dose administration of GNR-055	Baseline to Week 26, and 52
Serum neuromarkers	Changes in levels of serum neuromarkers after multiple-dose administration of GNR-055	Baseline to Week 24, and 52
CSF neuromarkers	Changes in levels of CSF neuromarkers after multiple-dose administration of GNR-055	Baseline to Week 24, and 52

Collaborators and Investigators

• Sponsor: AO GENERIUM
• Investigators: Study Director: Oksana A. Markova, MD, MSc, AO GENERIUM

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Connective Tissue Diseases; Genetic Diseases, Inborn; Intellectual Disability; Neurologic Manifestations; Mental Disorders; Cognitive Dysfunction; Cognition Disorders; Metabolic Diseases; Neurocognitive Disorders; Hunter syndrome; Neurobehavioral Manifestations; Lysosomal Storage Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Mucopolysaccharidosis type II; Metabolism, Inborn; Iduronate-2-sulfatase; Modified I2S protein; Mental Retardation, X-Linked
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Connective Tissue Diseases; Neurobehavioral Manifestations; Heredodegenerative Disorders, Nervous System; Mental Retardation, X-Linked; Intellectual Disability; Genetic Diseases, X-Linked; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Metabolic Diseases; Mucopolysaccharidosis II
• Other Study ID Numbers: IDB-MPS-II-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No