Mucopolysaccharidosis Type IIPhase 1NCT06475404
A Study of the Tolerance, Safety, and Pharmacokinetics of GNR-055 in Healthy Volunteers
A Phase 1 study testing verenafusp alfa 6 mg/kg, verenafusp alfa 9 mg/kg and verenafusp alfa 12 mg/kg 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 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Mucopolysaccharidosis Type II, Metabolic Diseases
- What is being tested?
- verenafusp alfa 6 mg/kg, verenafusp alfa 9 mg/kg and verenafusp alfa 12 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteRussia
- Study dates
- 6 Apr 2023to 20 Sep 2023
- 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 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men aged 18 to 45 years (inclusive) at the time of signing the Informed Consent Form;
- Body mass index (BMI) 18.5 to 29.9 kg/m2, body weight of 50 to 90 kg;
- A verified diagnosis as "healthy" (the diagnosis "healthy" is established based on 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);
Show all 22Show fewer
- 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 90 mm Hg or above 139 mm Hg; diastolic blood pressure (DBP) below 50 mm Hg or above 89 mm Hg; heart rate (HR) below 60 bpm or above 90 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 5 units of alcohol per week (1 unit of alcohol is equal to 30 ml of ethyl alcohol) OR history of alcoholism, drug addiction, or drug abuse;
- Alcohol exhale positive test;
- Drug addiction and positive urine analysis for potent and narcotic substances;
- Smoking more than 5 cigarettes per day;
- Any planned surgical intervention during the study period;
- Reluctance to comply with contraceptive methods;
- Vaccination (with any vaccine) within 30 days before signing the informed consent and/or the need for vaccination during the study period; 23. History of an autoimmune disease; 24. History of any cancer.
Trial locations and contacts
1 site in 1 country.
Russia1 site
State budgetary healthcare institution of the city of Moscow "City Clinic No. 2 of the Moscow Health Department"
Moscow, 117556
About this study
Official title: Open-label Multi-cohort Study of the Tolerability, Safety, and Pharmacokinetics of GNR-055 in Healthy Volunteers After a Single Intravenous Injection in Increasing Doses
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 (verenafusp alfa) is intended for enzyme replacement therapy (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 idursulfase (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), 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 (verenafusp alfa) is a modified enzyme I2S 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
- verenafusp alfa 6 mg/kg, verenafusp alfa 9 mg/kg, verenafusp alfa 12 mg/kg
- Keywords
- Mucopolysaccharidosis type II, Mucopolysaccharidoses, Metabolic Diseases, Lysosomal Storage Diseases, Carbohydrate Metabolism, Inborn, Metabolism, Genetic Diseases, 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.
verenafusp alfa 6 mg/kgBiological
Also called GNR-055
Single intravenous administration of 6 mg/kg of verenafusp alfa
verenafusp alfa 9 mg/kgBiological
Also called GNR-055
Single intravenous administration of 9 mg/kg of verenafusp alfa
verenafusp alfa 12 mg/kgBiological
Also called GNR-055
Single intravenous administration of 12 mg/kg of verenafusp alfa
| Study group | Role | What they receive |
|---|---|---|
| verenafusp alfa 6 mg/kg intravenously | Experimental | Single intravenous administration Receives: Biological: verenafusp alfa 6 mg/kg |
| verenafusp alfa 9 mg/kg intravenously | Experimental | Single intravenous administration Receives: Biological: verenafusp alfa 9 mg/kg |
| verenafusp alfa 12 mg/kg intravenously | Experimental | Single intravenous administration Receives: Biological: verenafusp alfa 12 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with Adverse Events
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic reactions, Infusion reactions, Antidrug antibody
Measured: Day 28
Secondary outcomes (2)
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
Analysis of equivalence of area under concentration-time curve from time 0 (predose) to the last quantifiable data point and to infinity
Measured: Day 4
Pharmacokinetics: Peak Plasma Concentration (Cmax)
Analysis of equivalence of Cmax
Measured: Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2024
- Study start6 Apr 2023
- Primary completion20 Sep 2023
- Study completion20 Sep 2023
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
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oksana A. Markova, MD, Study chair, JSC GENERIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06475404
- Sponsor's protocol ID
- IDB-MPS-I02
- Status last verified
- Jun 2024
- First submitted
- 20 Jun 2024
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Multi-cohort Study of the Tolerability, Safety, and Pharmacokinetics of GNR-055 in Healthy Volunteers After a Single Intravenous Injection in Increasing Doses
- ClinicalTrials.gov ID
- NCT06475404
- Acronym / sponsor ID
- IDB-MPS-I02
- Conditions
- Mucopolysaccharidosis Type II, Metabolic Diseases
- Keywords
- Mucopolysaccharidosis type II, Mucopolysaccharidoses, Metabolic Diseases, Lysosomal Storage Diseases, Carbohydrate Metabolism, Inborn, Metabolism, Genetic Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 6 Apr 2023 (actual)
- Primary completion
- 20 Sep 2023 (actual)
- Study completion
- 20 Sep 2023 (actual)
- First posted
- 26 Jun 2024 (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 (verenafusp alfa) is intended for enzyme replacement therapy (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 idursulfase (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), 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 (verenafusp alfa) is a modified enzyme I2S 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| verenafusp alfa 6 mg/kg intravenously | Experimental | Biological: verenafusp alfa 6 mg/kgSingle intravenous administration |
| verenafusp alfa 9 mg/kg intravenously | Experimental | Biological: verenafusp alfa 9 mg/kgSingle intravenous administration |
| verenafusp alfa 12 mg/kg intravenously | Experimental | Biological: verenafusp alfa 12 mg/kgSingle intravenous administration |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men aged 18 to 45 years (inclusive) at the time of signing the Informed Consent Form;
- Body mass index (BMI) 18.5 to 29.9 kg/m2, body weight of 50 to 90 kg;
- A verified diagnosis as "healthy" (the diagnosis "healthy" is established based on 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 (22 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 |
|---|---|---|
| verenafusp alfa 6 mg/kgAlso: GNR-055Single intravenous administration of 6 mg/kg of verenafusp alfa | Biological | verenafusp alfa 6 mg/kg intravenously |
| verenafusp alfa 9 mg/kgAlso: GNR-055Single intravenous administration of 9 mg/kg of verenafusp alfa | Biological | verenafusp alfa 9 mg/kg intravenously |
| verenafusp alfa 12 mg/kgAlso: GNR-055Single intravenous administration of 12 mg/kg of verenafusp alfa | Biological | verenafusp alfa 12 mg/kg intravenously |
Primary outcome
Proportion of participants with Adverse Events
Time frame: Day 28
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic reactions, Infusion reactions, Antidrug antibody
2 secondary outcomes
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
Time frame: Day 4
Pharmacokinetics: Peak Plasma Concentration (Cmax)
Time frame: Day 4
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 3 Jul 2024.
- Individual participant dataSharing planned: No
Related trials for Mucopolysaccharidosis Type II
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
Enrolling by invitationPhase 2/3
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Mucopolysaccharidosis II
Active, not recruitingPhase 3
A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)
Mucopolysaccharidosis II
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 1/2
A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)
Mucopolysaccharidosis IIIB
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 study chair
JSC GENERIUM
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 verenafusp alfa 6 mg/kg, verenafusp alfa 9 mg/kg and verenafusp alfa 12 mg/kg 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 22 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 3 Jul 2024. 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?
Proportion of participants with Adverse Events (time frame: Day 28). 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 3 Jul 2024.