Mucopolysaccharidosis Type IIPhase 2/3NCT05208281
A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
A Phase 2/3 study testing GNR-055 1.0-2.0-3.0 mg/kg, GNR-055 2.0 mg/kg and GNR-055 3.0 mg/kg in people with Mucopolysaccharidosis Type II and Metabolic Diseases, run by AO GENERIUM at 5 sites in Russia.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Mucopolysaccharidosis Type II, Metabolic Diseases
- What is being tested?
- GNR-055 1.0-2.0-3.0 mg/kg, GNR-055 2.0 mg/kg and GNR-055 3.0 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 5 sitesRussia
- Study dates
- 30 Nov 2021to Mar 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Russia5 sites
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)
Moscow, 119333
Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State Pediatric Medical University" of the Ministry of Health of the Russian Federation
Saint Petersburg, 194100
V.I. Vernadsky Crimean Federal University
Simferopol, 295007
State Budgetary Healthcare Institution Republican Medical Genetic Center
Ufa, 450076
State Autonomous Healthcare Institution of the Sverdlovsk Region Regional Children's Clinical Hospital
Yekaterinburg, 620149
About this study
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
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.
Read the 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).
- Conditions
- Mucopolysaccharidosis Type II, Metabolic Diseases
- Being tested
- GNR-055 1.0-2.0-3.0 mg/kg, GNR-055 2.0 mg/kg, GNR-055 3.0 mg/kg
- 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
- Medical subject headings
- Mucopolysaccharidosis II, Metabolic Diseases, Cognitive Dysfunction, Lysosomal Storage Diseases, Neurocognitive Disorders, Genetic Diseases, Inborn, Neurobehavioral Manifestations, Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GNR-055 1.0-2.0-3.0 mg/kgDrug
Also called GNR-055
Weekly IV infusion (lyophilized powder) 1.0-2.0-3.0 mg/kg
GNR-055 2.0 mg/kgDrug
Also called GNR-055
Weekly IV infusion (lyophilized powder) 2.0 mg/kg
GNR-055 3.0 mg/kgDrug
Also called GNR-055
Weekly IV infusion (lyophilized powder) 3.0 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Adult: GNR-055 | Experimental | GNR-055: 1.0-2.0-3.0 mg/kg Receives: Drug: GNR-055 1.0-2.0-3.0 mg/kg |
| Paediatric: GNR-055 2.0 mg/kg | Experimental | GNR-055 2.0 mg/kg Receives: Drug: GNR-055 2.0 mg/kg |
| Paediatric: GNR-055 3.0 mg/kg | Experimental | GNR-055 3.0 mg/kg Receives: Drug: GNR-055 3.0 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 56
Urine GAG excretion
Changes in levels of urine GAG excretion after multiple-dose administration of GNR-055
Measured: Baseline to Week 4, 8, 10, 26, and 52
Secondary outcomes (12)
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
Measured: Week 52
GAG level in CerebroSpinal Fluid (CSF)
Changes in levels of CSF GAG after multiple-dose administration of GNR-055
Measured: Baseline to Week 6, 10, 26, and 52
Serum GAG level
Changes in levels of serum GAG after multiple-dose administration of GNR-055
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to Week 26, and 52
Serum neuromarkers
Changes in levels of serum neuromarkers after multiple-dose administration of GNR-055
Measured: Baseline to Week 24, and 52
CSF neuromarkers
Changes in levels of CSF neuromarkers after multiple-dose administration of GNR-055
Measured: Baseline to Week 24, and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start30 Nov 2021
- Primary completion20 Dec 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis Type IIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Sequential Assignment
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oksana A. Markova, MD, MSc, Study director, AO GENERIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05208281
- Sponsor's protocol ID
- IDB-MPS-II-III
- Status last verified
- Sep 2026
- First submitted
- 14 Oct 2021
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05208281
- Acronym / sponsor ID
- IDB-MPS-II-III
- Conditions
- Mucopolysaccharidosis Type II, Metabolic Diseases
- Keywords
- Mucopolysaccharidosis type II, Cognitive Dysfunction, Metabolic Diseases, Lysosomal Storage Diseases, Neurocognitive Disorders, Metabolism, Inborn, Genetic Diseases, Inborn, Neurobehavioral Manifestations
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 20 Dec 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 26 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Sequential Assignment
| Arm | Type | Receives |
|---|---|---|
| Adult: GNR-055 | Experimental | Drug: GNR-055 1.0-2.0-3.0 mg/kgGNR-055: 1.0-2.0-3.0 mg/kg |
| Paediatric: GNR-055 2.0 mg/kg | Experimental | Drug: GNR-055 2.0 mg/kgGNR-055 2.0 mg/kg |
| Paediatric: GNR-055 3.0 mg/kg | Experimental | Drug: GNR-055 3.0 mg/kgGNR-055 3.0 mg/kg |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GNR-055 1.0-2.0-3.0 mg/kgAlso: GNR-055Weekly IV infusion (lyophilized powder) 1.0-2.0-3.0 mg/kg | Drug | Adult: GNR-055 |
| GNR-055 2.0 mg/kgAlso: GNR-055Weekly IV infusion (lyophilized powder) 2.0 mg/kg | Drug | Paediatric: GNR-055 2.0 mg/kg |
| GNR-055 3.0 mg/kgAlso: GNR-055Weekly IV infusion (lyophilized powder) 3.0 mg/kg | Drug | Paediatric: GNR-055 3.0 mg/kg |
Primary outcome
Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline to Week 56
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.
Urine GAG excretion
Time frame: Baseline to Week 4, 8, 10, 26, and 52
Changes in levels of urine GAG excretion after multiple-dose administration of GNR-055
12 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oksana A. Markova, MD, MSc study director
AO GENERIUM
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing GNR-055 1.0-2.0-3.0 mg/kg, GNR-055 2.0 mg/kg and GNR-055 3.0 mg/kg in people with Mucopolysaccharidosis Type II and Metabolic Diseases, run by AO GENERIUM at 5 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline to Week 56). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.