A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: GNR-055 1.0-2.0-3.0 mg/kg, GNR-055 2.0 mg/kg, GNR-055 3.0 mg/kg.
- Who it may be relevant to
- Registry conditions: Mucopolysaccharidosis Type II, Metabolic Diseases. Basic parameters: No limits · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Russia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
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
Overview
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.
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).
Interventions
- Drug GNR-055 1.0-2.0-3.0 mg/kg
Weekly IV infusion (lyophilized powder) 1.0-2.0-3.0 mg/kg - Drug GNR-055 2.0 mg/kg
Weekly IV infusion (lyophilized powder) 2.0 mg/kg - Drug GNR-055 3.0 mg/kg
Weekly IV infusion (lyophilized powder) 3.0 mg/kg
Primary outcome measures
- Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs) [Time frame: Baseline to Week 56]
- Urine GAG excretion [Time frame: Baseline to Week 4, 8, 10, 26, and 52]
Secondary outcome measures (12)
- Serum concentration of the GNR-055 [Time frame: Week 52]
- GAG level in CerebroSpinal Fluid (CSF) [Time frame: Baseline to Week 6, 10, 26, and 52]
- Serum GAG level [Time frame: Baseline to Week 4, 8, 10, 26, and 52]
- Large joint range of motion [Time frame: Week 8, 10, 26, and 52]
- Liver and spleen volumes (MRI) [Time frame: Baseline to Week 8, 10, 26, and 52]
- 6-minute walk test [Time frame: Baseline to Week 8, 10, 26, and 52]
- Left ventricular mass by EchoCG [Time frame: Baseline to Week 8, 10, 26, and 52]
- Lung Forced Vital Capacity (FVC) [Time frame: Baseline to Week 8, Week 26, and Week 52]
- Neurocognitive functions assessment [Time frame: Baseline to Week 12, 26, and 52]
- Brain white/gray matter structures (MRI) [Time frame: Baseline to Week 26, and 52]
- Serum neuromarkers [Time frame: Baseline to Week 24, and 52]
- CSF neuromarkers [Time frame: Baseline to Week 24, and 52]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Russia · 5 centers
- Federal State-Funded Healthcare Institution Central Clinical Hospital of the Russian Acade — Moscow
- Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State — Saint Petersburg
- V.I. Vernadsky Crimean Federal University — Simferopol
- State Budgetary Healthcare Institution Republican Medical Genetic Center — Ufa
- State Autonomous Healthcare Institution of the Sverdlovsk Region Regional Children's Clini — Yekaterinburg
Identifiers
NCT: NCT05208281 · IDB-MPS-II-III