Tolerance, Pharmacokinetics / Pharmacodynamics (PK / PD) and Immunogenicity of Pegylated Uric Acid Oxidase for Injection in Healthy Adults and Hyperuricemia Volunteers

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Tolerance, Pharmacokinetics / Pharmacodynamics (PK / PD) and Immunogenicity of Pegylated Uric Acid Oxidase for Injection in Healthy Adults and Hyperuricemia Volunteers

A randomized, double-blind, placebo-controlled study of tolerance, pharmacokinetic / pharmacodynamics (PK / PD) and immunogenicity of single administration of PEG uric oxidase for injection in healthy adults and hyperuricemia volunteers.

Study Overview

• Status: Recruiting
• Conditions: Hyperuricemia
• Intervention / Treatment: Drug: Placebo; Drug: Polyglycol lated urate oxidase for injection

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266003
      • Recruiting
      • The affiliated hospital of Qingdao university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers:

  • Subjects understand well trial purpose, nature, content, process and possible adverse reactions, and voluntarily sign an informed consent form.
  • Serum uric acid level<360 µ mol / L twice on different days.
  • Healthy male or female aged between 18 and 60 years old (including the critical value).
  • The body mass index is in the range of 18-30kg/m2 (including the critical value). The weight of male is not less than 50 kg, and that of female is not less than 45 kg (including the critical value).
  • Subjects who had not any medical history of cardiovascular, digestive, respiratory, nervous, haemal diseases or hepatic/renal impairment.The following examination show that the indicators are normal or abnormal without clinical significance. The examination including: physical examination, 12-lead ECG, vital sign measurements and laboratory safety tests .
  • The subjects have no family planning within 6 months and could select contraceptive method. They have no sperm and egg donation program.
  • Before the study, all subjects have been informed of the study's purpose, protocal, benefits, and risks, and signed the informed consent voluntarily.
  • The blood pregnancy test of female subjects was negative, the menstrual cycle was regular, and the menstrual bleeding period was 3 ~ 7 days.

Patients with hyperuricemia:

• Patients with hyperuricemia ,male or female aged between 18 and 60 years old (including the critical value).
• Stop uric acid lowering treatment for at least 7 days, and 480≤UA≤540µmol/L twice on different days within 7 days.
• The body mass index is in the range of 18-30kg/m2 (including the critical value). The weight of male is not less than 50 kg, and that of female is not less than 45 kg (including the critical value).
• Before the study, all subjects have been informed of the study's purpose, protocal, benefits, and risks, and signed the informed consent voluntarily.
• The blood pregnancy test of female subjects was negative, the menstrual cycle was regular, and the menstrual bleeding period was 3 ~ 7 days.

Exclusion Criteria:

• Healthy volunteers:

  • A history of drug allergy, or allergic allergic disease, or known to be allergic to the test drug or its excipients or the same type of drug;
  • Hepatitis (including hepatitis B and C), positive screening results for AIDS or syphilis;
  • Any history of acute or chronic illness that might affect drug absorption, and/or metabolism;
  • Any history of drug abuse in the past 12 months prior to screening;
  • Any history of alcohol abuse 3 months prior to screening or moderate drinkers (drink more 2 units per day or 14 units per week);
  • Smoking more than 5 cigarettes per day during the 3 months prior to screening;
  • Blood donation, massive blood loss (#400mL) or enrolled in other clinical trials 3 months prior to screening;
  • Any use of other prescription drugs (including contraceptive)#over-the counter drugs, Chinese herbal medicine, health care products and 14 days prior to medication for this study;
  • Any history of postural hypotension, syncope, or amaurosis;
  • 6-glucose phosphate dehydrogenase (G6PD) deficiency;
  • Lactating or pregnant women

Patients with hyperuricemia:

• Using uric acid lowering drugs and unwilling to stop existing drugs.
• Ultrasonic examination of the metatarsal-toe joint suggested the presence of tophi.
• Serum CA72-4 level ≥7.5U / mL.
• History of organic heart disease (symptomatic cardiac insufficiency with grade II-IV).
• Patients with refractory hypertension.
• Patients with malignant tumors (treatment or not).
• Patients with organ transplantation treated with immunosuppressants.
• Any history of drug abuse in the past 12 months prior to screening;
• Any history of alcohol abuse 3 months prior to screening or moderate drinkers (drink more 2 units per day or 14 units per week).
• Smoking more than 5 cigarettes per day during the 3 months prior to screening.
• A history of drug allergy, or allergic allergic disease, or known to be allergic to the test drug or its excipients or the same type of drug.
• Any history of acute or chronic illness that might affect drug absorption, and/or metabolism.
• 6-glucose phosphate dehydrogenase (G6PD) deficiency.
• Once treated with urate oxidase.
• Subjects had an uncorrected dehydration, acidosis, hypotension, renal insufficiency, or were using drugs with nephrotoxicity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PEGylated Urate Oxidase for Injection; PEGylated Urate Oxidase for Injection，specification:5mg，Single dose ascending.Healthy subjects were divided into three dose groups (0.5mg, 1mg, 2mg), and hyperuricemia patients were divided into four dose groups (2mg, 4mg, 8mg, 12 mg), with increasing dose design.Each group will receive the experimental drug in 6 subjects.	Drug: Polyglycol lated urate oxidase for injection; Single dose escalation
PLACEBO_COMPARATOR: Placebo; Placebo , specification: 5mg,Single dose. Groups received the placebo in 2 patients per group.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	Evaluation of Peak Plasma Concentration (Cmax)	500 days
Maximum tolerated dose Maximum tolerated dose	Maximum tolerated dose Maximum tolerated dose for a single dose	500 days
Area under the plasma concentration versus time curve (AUC)0-t	Evaluation of Area under the plasma concentration versus time curve (AUC)0-t	500 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence rate of Adverse Events	Adverse events were recorded to evaluate the safety of the studied drugs	500 day
Immunogenicity	Antidrug antibody detection	500day

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Investigators: Principal Investigator: Changgui Li, Doctor, The affiliated hospital of Qingdao university

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 8, 2021
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: February 4, 2022
• First Posted (ACTUAL): February 7, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Antirheumatic Agents; Gout Suppressants; Rasburicase
• Other Study ID Numbers: XZ-PEG-UOX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the technical achievements and outcomes of this trial are owned by Revised Biomedical (Hangzhou) Research Institute Co., Ltd. and the research center. The research center can not publish any academic papers without the consent of the sponsor.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No