Mucopolysaccharidosis Type IIPhase 1NCT04539340
A Multi-cohort Study of the Tolerance, Safety, and Pharmacokinetics of GNR-055 in Healthy Volunteers
A Phase 1 study testing GNR-055 in people with Mucopolysaccharidosis Type II and Metabolic Diseases, run by AO GENERIUM at 1 site in Russia.
Trial summary
It is a phase I open-label single-dose, dose-escalation cohort study to evaluate of the tolerance, safety, and pharmacokinetics of GNR-055 in healthy volunteers Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Mucopolysaccharidosis Type II, Metabolic Diseases
- What is being tested?
- GNR-055
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteRussia
- Study dates
- 28 Feb 2020to 8 Sep 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men aged 18 to 50 years (inclusive) at the time of signing the Informed Consent Form;
- Body mass index (BMI) 18.5 to 30 kg/m2, body weight of 50 to 90 kg;
- A verified diagnosis as "healthy" (the diagnosis "healthy" is established on the basis of a detailed medical history, in the absence of deviations from normal values during a clinical examination, including measurement of blood pressure, respiratory rate, heart rate, body temperature, laboratory and instrumental (ECG) examination data);
- A written informed consent to participate in the study in accordance with applicable laws in place and compliance with all the procedures and requirements/restrictions provided for by the study protocol;
- Consent to use adequate methods of contraception (double barrier method-male or female (for partners of male research volunteers), condom with spermicide, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, cervical cap with spermicide).
Who cannot join
- Known hypersensitivity to idursulfase and/or to the medicinal product excipients;
- Burdened allergy history;
- Drug intolerance;
- History of seizures;
- Deposit injections or implants use of any other medicinal product three months before the Screening Visit;
- An unusual way of living (night working, extreme physical activity);
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- Diarrhea dehydration, vomiting, or other causes within 24 hours before the Screening Visit;
- Deviations from the normal values of the clinical, laboratory, and ECG examinations;
- If there are acute or chronic diseases of the cardiovascular, bronchopulmonary, nervous, immune, and endocrine systems, diseases of the gastrointestinal tract, liver and biliary tract, kidney and urinary tract, blood and lymphatic system, a history of mental illness;
- Positive results for hepatitis B or C markers, human immunodeficiency virus (HIV), and syphilis;
- Acute infectious diseases less than four weeks before the Screening Visit;
- Regular administration of medicinal products less than two weeks before the Screening Visit;
- Systolic blood pressure (SBP) below 100 mm Hg or above 140 mm Hg; diastolic blood pressure (DBP) below 70 mm Hg or above 90 mm Hg; HR below 60 bpm or above 80 bpm;
- Blood donation (450 mL or more of blood or plasma) less than three months before the Screening Visit;
- Participation in human clinical studies of medicinal products less than three months before the Screening Visit;
- Consumption of more than 10 units of alcohol per week (1 unit of alcohol is equivalent to 0.5 L of beer, 200 mL of dry wine, or 50 mL of strong spirits) OR history of alcoholism;
- Alcohol exhale positive test;
- Drug addiction, toxic substance abuse, a positive urine analysis for potent and narcotic substances, including cocaine, cannabis, amphetamine, barbiturates, benzodiazepines, and opioids;
- Smoking more than 10 cigarettes per day;
- Other reasons that, in the opinion of the investigator, prevent a volunteer from participating in the study or cause an unreasonable risk.
Trial locations and contacts
1 site in 1 country.
Russia1 site
FSAEI HE "I.M. Sechenov First Moscow State Medical University" of the Ministry of Health of Russian Federation
Moscow, 119991
About this study
Official title: An Open-label Multi-cohort Dose-escalation Study to Evaluate the Tolerance, Safety, and Pharmacokinetics of GNR-055 (GENERIUM JSC, Russia) in Healthy Volunteers With a Single Intravenous Administration
It is a phase I open-label single-dose, dose-escalation cohort study to evaluate of the tolerance, safety, and pharmacokinetics of GNR-055 in healthy volunteers
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 lysosomal storage disease with an X-linked recessive inheritance type, which is characterized by a decrease in the activity of the lysosomal enzyme iduronate-2-sulfatase (I2S), caused by a mutation in the IDS gene. Enzyme deficiency leads to the accumulation of glycosaminoglycans (GAG) in lysosomes, mainly fractions of heparan and dermatan sulfates. Because of the insufficient activity of iduronate sulfatase participating in the first stage of catabolism of GAG, they accumulate 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 modified enzyme iduronate-2-sulfatase capable of penetrating the blood-brain barrier and thus it is expected to prevent neurodegenerative consequences and the development of cognitive deficit in the future that will allow achieving a significant improvement in the life quality and expectancy of patients with MPS II
- Conditions
- Mucopolysaccharidosis Type II, Metabolic Diseases
- Being tested
- GNR-055
- Keywords
- Mucopolysaccharidosis type II, Mucopolysaccharidoses, Metabolic Diseases, Lysosomal Storage Diseases, Carbohydrate Metabolism, Inborn, Metabolism, Inborn, Genetic Diseases, Inborn, Neurobehavioral Manifestations, Neurologic Manifestations, Genetic Diseases, X-Linked
- Medical subject headings
- Mucopolysaccharidosis II, Metabolic Diseases, Mucopolysaccharidoses, Lysosomal Storage Diseases, Genetic Diseases, Inborn, Neurobehavioral Manifestations, Neurologic Manifestations, Genetic Diseases, X-Linked
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GNR-055Biological
Single intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 GNR-055 (0.3 mg/kg) | Other | GNR-055 (0.3 mg/kg) Single intravenous administration GNR-055 Receives: Biological: GNR-055 |
| Cohort 2 GNR-055 (0.5 mg/kg) | Other | GNR-055 (0.5 mg/kg) Single intravenous administration GNR-055 Receives: Biological: GNR-055 |
| Cohort 3 GNR-055 (1 mg/kg) | Other | GNR-055 (1 mg/kg) Single intravenous administration GNR-055 Receives: Biological: GNR-055 |
| Cohort 4 GNR-055 ( 2 mg/kg) | Other | GNR-055 ( 2 mg/kg) Single intravenous administration GNR-055 Receives: Biological: GNR-055 |
| Cohort 5 GNR-055 (3 mg/kg) | Other | GNR-055 (3 mg/kg) Single intravenous administration GNR-055 Receives: Biological: GNR-055 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.
Measured: Day 7 ± 1
Secondary outcomes (8)
Serum pharmacokinetic parameters of GNR-055
Serum concentration GNR-055, Pharmacokinetic parameters
Measured: Day 2
Cmax - Maximum Serum Concentration
Pharmacokinetic parameters
Measured: Day 2
AUC - Area Under the Curve
Pharmacokinetic parameters
Measured: Day 2
Т1/2 - Half-life
Pharmacokinetic parameters
Measured: Day 2
Kel - Elimination rate constant
Pharmacokinetic parameters
Measured: Day 2
MRT - Mean residence time
Pharmacokinetic parameters
Measured: Day 2
Cl - Clearance
Pharmacokinetic parameters
Measured: Day 2
Vz - volume of distribution
Pharmacokinetic parameters
Measured: Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2020
- Study start28 Feb 2020
- Primary completion8 Sep 2020
- Study completion8 Sep 2020
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04539340
- Sponsor's protocol ID
- IDB-MPS-I
- Status last verified
- Aug 2020
- First submitted
- 28 Aug 2020
- Last updated
- 14 Oct 2020
- 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 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Multi-cohort Dose-escalation Study to Evaluate the Tolerance, Safety, and Pharmacokinetics of GNR-055 (GENERIUM JSC, Russia) in Healthy Volunteers With a Single Intravenous Administration
- ClinicalTrials.gov ID
- NCT04539340
- Acronym / sponsor ID
- IDB-MPS-I
- Conditions
- Mucopolysaccharidosis Type II, Metabolic Diseases
- Keywords
- Mucopolysaccharidosis type II, Mucopolysaccharidoses, Metabolic Diseases, Lysosomal Storage Diseases, Carbohydrate Metabolism, Inborn, Metabolism, Inborn, Genetic Diseases, Inborn, Neurobehavioral Manifestations
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2020 (actual)
- Primary completion
- 8 Sep 2020 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 7 Sep 2020 (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.
It is a phase I open-label single-dose, dose-escalation cohort study to evaluate of the tolerance, safety, and pharmacokinetics of GNR-055 in healthy volunteers
Detailed description
GNR-055 is intended for ERT in patient with Mucopolysaccharidosis type II (MPS II), or Hunter syndrome. MPS II is a lysosomal storage disease with an X-linked recessive inheritance type, which is characterized by a decrease in the activity of the lysosomal enzyme iduronate-2-sulfatase (I2S), caused by a mutation in the IDS gene. Enzyme deficiency leads to the accumulation of glycosaminoglycans (GAG) in lysosomes, mainly fractions of heparan and dermatan sulfates. Because of the insufficient activity of iduronate sulfatase participating in the first stage of catabolism of GAG, they accumulate 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 modified enzyme iduronate-2-sulfatase capable of penetrating the blood-brain barrier and thus it is expected to prevent neurodegenerative consequences and the development of cognitive deficit in the future that will allow achieving a significant improvement in the life quality and expectancy of patients with MPS II
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 GNR-055 (0.3 mg/kg) | Other | Biological: GNR-055GNR-055 (0.3 mg/kg) Single intravenous administration GNR-055 |
| Cohort 2 GNR-055 (0.5 mg/kg) | Other | Biological: GNR-055GNR-055 (0.5 mg/kg) Single intravenous administration GNR-055 |
| Cohort 3 GNR-055 (1 mg/kg) | Other | Biological: GNR-055GNR-055 (1 mg/kg) Single intravenous administration GNR-055 |
| Cohort 4 GNR-055 ( 2 mg/kg) | Other | Biological: GNR-055GNR-055 ( 2 mg/kg) Single intravenous administration GNR-055 |
| Cohort 5 GNR-055 (3 mg/kg) | Other | Biological: GNR-055GNR-055 (3 mg/kg) Single intravenous administration GNR-055 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men aged 18 to 50 years (inclusive) at the time of signing the Informed Consent Form;
- Body mass index (BMI) 18.5 to 30 kg/m2, body weight of 50 to 90 kg;
- A verified diagnosis as "healthy" (the diagnosis "healthy" is established on the basis of a detailed medical history, in the absence of deviations from normal values during a clinical examination, including measurement of blood pressure, respiratory rate, heart rate, body temperature, laboratory and instrumental (ECG) examination data);
- A written informed consent to participate in the study in accordance with applicable laws in place and compliance with all the procedures and requirements/restrictions provided for by the study protocol;
- Consent to use adequate methods of contraception (double barrier method-male or female (for partners of male research volunteers), condom with spermicide, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, cervical cap with spermicide).
Key exclusion criteria (20 listed)
- Known hypersensitivity to idursulfase and/or to the medicinal product excipients;
- Burdened allergy history;
- Drug intolerance;
- History of seizures;
- Deposit injections or implants use of any other medicinal product three months before the Screening Visit;
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-055Single intravenous administration | Biological | Cohort 1 GNR-055 (0.3 mg/kg), Cohort 2 GNR-055 (0.5 mg/kg), Cohort 3 GNR-055 (1 mg/kg), Cohort 4 GNR-055 ( 2 mg/kg), Cohort 5 GNR-055 (3 mg/kg) |
Primary outcome
Number of participants with Adverse Events
Time frame: Day 7 ± 1
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.
8 secondary outcomes
Serum pharmacokinetic parameters of GNR-055
Time frame: Day 2
Cmax - Maximum Serum Concentration
Time frame: Day 2
AUC - Area Under the Curve
Time frame: Day 2
Т1/2 - Half-life
Time frame: Day 2
Kel - Elimination rate constant
Time frame: Day 2
MRT - Mean residence time
Time frame: Day 2
Cl - Clearance
Time frame: Day 2
Vz - volume of distribution
Time frame: Day 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GNR-055 in people with Mucopolysaccharidosis Type II and Metabolic Diseases, run by AO GENERIUM at 1 site 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 20 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: finished, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of participants with Adverse Events (time frame: Day 7 ± 1). 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 14 Oct 2020.