Back to resultsA Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
Primary Purpose
Mucopolysaccharidosis Type II, Metabolic Diseases
Status
Recruiting
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
GNR-055 1.0-2.0-3.0 mg/kg
GNR-055 2.0 mg/kg
GNR-055 3.0 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis Type II focused on measuring 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
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.
Sites / Locations
- State Autonomous Healthcare Institution of the Sverdlovsk Region Regional Children's Clinical HospitalRecruiting
- 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)
- V.I. Vernadsky Crimean Federal UniversityRecruiting
- Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State Pediatric Medical University" of the Ministry of Health of the Russian Federation
- State Budgetary Healthcare Institution Republican Medical Genetic CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Adult: GNR-055
Paediatric: GNR-055 2.0 mg/kg
Paediatric: GNR-055 3.0 mg/kg
Arm Description
GNR-055: 1.0-2.0-3.0 mg/kg
GNR-055 2.0 mg/kg
GNR-055 3.0 mg/kg
Outcomes
Primary Outcome Measures
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.
Urine GAG excretion
Changes in levels of urine GAG excretion after multiple-dose administration of GNR-055
Secondary Outcome Measures
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
GAG level in CerebroSpinal Fluid (CSF)
Changes in levels of CSF GAG after multiple-dose administration of GNR-055
Serum GAG level
Changes in levels of serum GAG after multiple-dose administration of GNR-055
Large joint range of motion
Changes over time in the large joint range of motion after multiple-dose administration of GNR-055
Liver and spleen volumes (MRI)
Changes over time in liver and spleen volume according to ultrasound/MRI after multiple-dose administration of GNR-055
6-minute walk test
Changes over time in the results of the 6-minute walk test after multiple-dose administration of GNR-055
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
Lung Forced Vital Capacity (FVC)
Changes over time in FVC according to spirometry after multiple-dose administration of GNR-055
Neurocognitive functions assessment
Changes over time in neurocognitive functions after multiple-dose administration of GNR-055
Brain white/gray matter structures (MRI)
Changes over time in the quantitative MRI brain structure parameters after multiple-dose administration of GNR-055
Serum neuromarkers
Changes in levels of serum neuromarkers after multiple-dose administration of GNR-055
CSF neuromarkers
Changes in levels of CSF neuromarkers after multiple-dose administration of GNR-055
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05208281
Brief Title
A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
March 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AO GENERIUM
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, 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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Model Description
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Adult: GNR-055
Arm Type
Experimental
Arm Description
GNR-055: 1.0-2.0-3.0 mg/kg
Arm Title
Paediatric: GNR-055 2.0 mg/kg
Arm Type
Experimental
Arm Description
GNR-055 2.0 mg/kg
Arm Title
Paediatric: GNR-055 3.0 mg/kg
Arm Type
Experimental
Arm Description
GNR-055 3.0 mg/kg
Intervention Type
Drug
Intervention Name(s)
GNR-055 1.0-2.0-3.0 mg/kg
Other Intervention Name(s)
GNR-055
Intervention Description
Weekly IV infusion (lyophilized powder) 1.0-2.0-3.0 mg/kg
Intervention Type
Drug
Intervention Name(s)
GNR-055 2.0 mg/kg
Other Intervention Name(s)
GNR-055
Intervention Description
Weekly IV infusion (lyophilized powder) 2.0 mg/kg
Intervention Type
Drug
Intervention Name(s)
GNR-055 3.0 mg/kg
Other Intervention Name(s)
GNR-055
Intervention Description
Weekly IV infusion (lyophilized powder) 3.0 mg/kg
Primary Outcome Measure Information:
Title
Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline to Week 56
Title
Urine GAG excretion
Description
Changes in levels of urine GAG excretion after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 4, 8, 10, 26, and 52
Secondary Outcome Measure Information:
Title
Serum concentration of the GNR-055
Description
Assessment of the serum concentration of GNR-055 and calculation of Cmax, AUC, T1/2, Cl et other parameters after multiple-dose administration
Time Frame
Week 52
Title
GAG level in CerebroSpinal Fluid (CSF)
Description
Changes in levels of CSF GAG after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 6, 10, 26, and 52
Title
Serum GAG level
Description
Changes in levels of serum GAG after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 4, 8, 10, 26, and 52
Title
Large joint range of motion
Description
Changes over time in the large joint range of motion after multiple-dose administration of GNR-055
Time Frame
Week 8, 10, 26, and 52
Title
Liver and spleen volumes (MRI)
Description
Changes over time in liver and spleen volume according to ultrasound/MRI after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 8, 10, 26, and 52
Title
6-minute walk test
Description
Changes over time in the results of the 6-minute walk test after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 8, 10, 26, and 52
Title
Left ventricular mass by EchoCG
Description
Changes over time in the left ventricular mass according to Echocardiography (Echo-CG) after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 8, 10, 26, and 52
Title
Lung Forced Vital Capacity (FVC)
Description
Changes over time in FVC according to spirometry after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 8, Week 26, and Week 52
Title
Neurocognitive functions assessment
Description
Changes over time in neurocognitive functions after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 12, 26, and 52
Title
Brain white/gray matter structures (MRI)
Description
Changes over time in the quantitative MRI brain structure parameters after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 26, and 52
Title
Serum neuromarkers
Description
Changes in levels of serum neuromarkers after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 24, and 52
Title
CSF neuromarkers
Description
Changes in levels of CSF neuromarkers after multiple-dose administration of GNR-055
Time Frame
Baseline to Week 24, and 52
10. Eligibility
Sex
Male
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Svetlana B. Korotkova, MD, PhD
Phone
+7(495) 988 47 94
Ext
7096
Email
sbkorotkova@generium.ru
First Name & Middle Initial & Last Name or Official Title & Degree
Oksana A. Markova, MD, MSc
Phone
+7(495) 988 47 94
Ext
7077
Email
oamarkova@generium.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oksana A. Markova, MD, MSc
Organizational Affiliation
AO GENERIUM
Official's Role
Study Director
Facility Information:
Facility Name
State Autonomous Healthcare Institution of the Sverdlovsk Region Regional Children's Clinical Hospital
City
Ekaterinburg
ZIP/Postal Code
620149
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
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)
City
Moscow
ZIP/Postal Code
119333
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
V.I. Vernadsky Crimean Federal University
City
Simferopol
ZIP/Postal Code
295007
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State Pediatric Medical University" of the Ministry of Health of the Russian Federation
City
St. Petersburg
ZIP/Postal Code
194100
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
State Budgetary Healthcare Institution Republican Medical Genetic Center
City
Ufa
ZIP/Postal Code
450076
Country
Russian Federation
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
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