A Study to Assess the Safety and Tolerability of SSS11 in Healthy Subjects.

Study Overview
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Brief Summary
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SSS11 is pegsiticase consisting of a recombinant uricase conjugated to multiple 20kDa PEG molecules. The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single dose SSS11 administered intravenously in healthy volunteers.

Detailed Description
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Objectives: Primary: • To assess the safety, tolerability of single dose SSS11 in healthy subjects Secondary: • To assess the pharmacokinetics, pharmacodynamics and immunogenicity of SSS-11 in healthy subjects Enrollment and Number of Arms (planned): 40 subjects will be assigned into 5 dosing cohorts (1.5, 3, 6, 12 and 24mg) with 5-10 subjects each. Original primary outcome Measures: Safety: Physical exam，ECG，Clinical laboratory tests，AE，SAE Tolerance assessment：MDT，DLT Original secondary outcome Measures: pharmacokinetics: Cmax, Tmax, AUC, CL, Vd, t1/2 pharmacodynamics: level of serum uric acid Immunogenicity ：anti-SSS11, anti-uricase and anti-PEG antibodies

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Single-dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSS11 Administered Intravenously in Healthy Volunteers.

Conditions
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Gout

Intervention / Treatment
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* Biological: SSS11
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Males and females, 18-45 years of age at time of consent; 2. Subjects are in good health, without any clinical significant symptoms or laboratory test; 3. Having a body mass index between 19 and 28 kilogram per meter square (kg/m²); 4. Capable of giving written informed consent 5. Understanding and being willing to comply with the requirements of protocol, participate to complete the study; 6. Having recovered if received a surgery before . Exclusion criteria： Allergic condition or having the history of allergic reactions to any drugs, pegylated products, or more than two substances; Use of any medicine within 4 weeks or shorter than 5 half-lives; Use of any medicine within 12 weeks, which is harm to any organ; Participated in any other clinical trial within 12 weeks; History of blood donation within 12 weeks; History of glucose-6-phosphate dehydrogenase deficiency; History of catalase deficiency; Any significant disease, including but not limited to the following: digestive system, cardiovascular system, respiratory system, urinary system, musculoskeletal system, endocrine system, neuropsychiatry system, hematological system, immune system, metabolic system abnormity. Abnormal significance clinical laboratory tests within 2 weeks such as routine blood test and urinalysis, blood chemistry, ECG. Positive serology for hepatitis B surface antigen , or antibodies to hepatitis C, or HIV and syphilis; Pregnancy, planning pregnancy, or breastfeeding; Positive pregnancy test; Male subject without effective contraception or his partner intend to be pregnant within 6 months; History of mental disorder or disabilities legally; History of alcohol abusing during the last 6 months; More than 5 cigarettes per day during the last 6 months; Positive drug abuse or alcohol test; More than 1L of strong tea, coffee or caffeine drink per day; Can't understand the content of informed consent form ; Any condition, which investigators consider, is not fit for the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SSS11, 1.5mg<br>SSS11, 1.5mg, iv, single dose at Day 1; | Biological: SSS11<br>* IV infusion for 60 min.<br>* Other names: pegsiticase;Other: placebo<br>* IV infusion for 60 min.<br>|
| Experimental: SSS11, 3.0mg<br>SSS11, 3.0mg, iv, single dose at Day 1; | Biological: SSS11<br>* IV infusion for 60 min.<br>* Other names: pegsiticase;Other: placebo<br>* IV infusion for 60 min.<br>|
| Experimental: SSS11, 6.0mg<br>SSS11, 6.0mg, iv, single dose at Day 1; | Biological: SSS11<br>* IV infusion for 60 min.<br>* Other names: pegsiticase;Other: placebo<br>* IV infusion for 60 min.<br>|
| Experimental: SSS11, 12.0mg<br>SSS11, 12.0mg, iv, single dose at Day 1; | Biological: SSS11<br>* IV infusion for 60 min.<br>* Other names: pegsiticase;Other: placebo<br>* IV infusion for 60 min.<br>|
| Experimental: SSS11, 24.0mg<br>SSS11, 24.0mg, iv, single dose at Day 1; | Biological: SSS11<br>* IV infusion for 60 min.<br>* Other names: pegsiticase;Other: placebo<br>* IV infusion for 60 min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of adverse events | incidence of adverse events | baseline to 4 weeks | 
| maximum tolerable dose | maximum tolerable dose | baseline to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| peak plasma concentration | peak plasma concentration | baseline to 4 weeks | 
| area under the plasma concentration versus time curve | area under the plasma concentration versus time curve | baseline to 4 weeks | 
| level of serum uric acid | level of serum uric acid | baseline to 4 weeks | 
| Immunogenicity | anti-SSS11 | baseline to 52 weeks |