Clinical trial NCT05226013: Tolerance, Pharmacokinetics / Pharmacodynamics (PK / PD) and Immunogenicity of Pegylated Uric Acid Oxidase for Injection in Healthy Adults and Hyperuricemia Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hyperuricemia
Lead sponsor: The Affiliated Hospital of Qingdao University
Sponsor class: OTHER
First posted: 2022-02-07
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: 500 days
measure: Maximum tolerated dose Maximum tolerated dose
timeFrame: 500 days
measure: Area under the plasma concentration versus time curve (AUC)0-t
timeFrame: 500 days
Secondary outcomes:
measure: Occurrence rate of Adverse Events
timeFrame: 500 day
measure: Immunogenicity
timeFrame: 500day
Other outcomes:
Locations:
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
Study officials:
affiliation: The Affiliated Hospital of Qingdao University
name: Yu Cao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Hospital of Qingdao University
name: Changgui Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: