A Multi-cohort Study of the Tolerance, Safety, and Pharmacokinetics of GNR-055 in Healthy Volunteers

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Brief Title

A Multi-cohort Study of the Tolerance, Safety, and Pharmacokinetics of GNR-055 in Healthy Volunteers

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

Brief 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
    

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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of participants with Adverse Events

Secondary Outcome

 Serum pharmacokinetic parameters of GNR-055

Condition

Mucopolysaccharidosis Type II

Intervention

GNR-055

Study Arms / Comparison Groups

 Cohort 1 GNR-055 (0.3 mg/kg)
Description:  GNR-055 (0.3 mg/kg) Single intravenous administration GNR-055

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

20

Start Date

February 28, 2020

Completion Date

September 8, 2020

Primary Completion Date

September 8, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  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).

        Exclusion Criteria:

          -  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);

          -  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.
      

Gender

Male

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, , 

Location Countries

Russian Federation

Location Countries

Russian Federation

Administrative Informations


NCT ID

NCT04539340

Organization ID

IDB-MPS-I


Responsible Party

Sponsor

Study Sponsor

AO GENERIUM


Study Sponsor

, , 


Verification Date

August 2020