Clinical trial NCT05302388: A Study Exploring Efficacy of Pegloticase in Subjects With Asymptomatic Hyperuricemia
Official title: A Phase I Randomized, Double-blind, Placebo-controlled, Dose-increasing Single Dose Study Evaluating the Safety, Tolerability，Pharmacokinetics and Pharmacodynamics Analysis of Pegloticase in Subjects With Asymptomatic Hyperuricemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asymptomatic Hyperuricemia
Keywords: Hyperuricemia
Pegloticase
Safety
Tolerability
Lead sponsor: Shanghai Institute Of Biological Products
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Bengbu Medical University
First posted: 2022-03-31
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a phase I randomized, double-blind, placebo-controlled and dose-increasing single dosing study.
Primary purpose: TREATMENT

Brief summary: The main purpose To evaluate the safety and tolerability of pegloticase in subjects with asymptomatic hyperuricemia by single intravenous infusion at different doses, and to provide a basis for multiple doses of Pegloticase in subjects with asymptomatic hyperuricemia.

A secondary purpose To evaluate the pharmacokinetics, pharmacodynamics and immunogenicity of Pegloticase with single-pass intravenous drip in subjects with asymptomatic hyperuricemia.

Exploratory purpose Plasma uricase activity (pUox) analysis of pegloticase with single-pass intravenous drip in subjects with asymptomatic hyperuricemia.

Detailed description: To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics analysis of pegloticase in subjects with asymptomatic hyperuricemia.

This is a phase I randomized, double-blind, placebo-controlled and dose-increasing single dosing study. Five dose groups of 1, 2, 4, 8 or 12 mg were planned to explore the most appropriate dose and to provide a basis for multiple doses of Pegloticase in subjects with asymptomatic hyperuricemia.

Eligibility criteria: Inclusion Criteria:

* The subjects voluntarily participated in the study and signed the informed consent.
* Male and female aged between 18 and 65 years old , regardless of gender.
* Male weight ≥50 kg, female weight ≥45 kg, body mass index (BMI) in the range of (19-30) kg/m2 (including 19 and 30), and no central obesity (waist circumference \<90 cm for men, waist circumference \<85 cm for women);
* Patients diagnosed as "hyperuricemia" according to The Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019), namely, patients whose blood uric acid level exceeds 480 μmol/L twice on other days, and no clinical symptoms related to hyperuricemia such as arthritis;
* Agree to use effective contraceptive methods (including but not limited to abstinence, physical or hormonal contraception, but not hormonal contraception during the study) from signing the informed consent form until 6 months after the infusion of the study drug;
* The subjects can attend the interview on time and complete the interview content.

Exclusion Criteria:

* People who have a history of gout and are using or have used other medications to control uric acid levels in the last 3 months, Asymptomatic hyperuricemia patients who stopped taking uricate-lowering drugs for more than 3 months were excluded.
* Secondary hyperuricemia (such as kidney disease, blood system disease, tumor chemotherapy or drug induced).
* Urolithiasis, or renal, ureteral calculi, urate crystal deposition indicated by ultrasound during screening; The presence of tophi or joint/bursa involvement was indicated by junction ultrasonography.
* Autoimmune disease, allergic disease, prior known food or drug allergy.
* Allergic reactions to recombinant proteins or pig products, or to uricase, polyethylene glycol, corticosteroids and antihistamines.
* Patients who have previously been treated with pegyluricase or other recombinant uricase, or who have been treated with other pegylated biological products.
* Patients have unstable angina, severe arrhythmias requiring drug intervention, congestive heart failure (NYHA grade≥Ⅱ), uncontrolled hypertension (over 150/95 mmHg), poor glycemic control in diabetics ( HbA1c≥7%), end-stage renal disease (CKD4-5), acute stroke, chest imaging suggesting active or severe lung disease, requiring dialysis, organ transplant recipients, and patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
* Serum creatinine was 1.5 times higher than the upper limit of normal value, and serum transaminase baseline level was 1.5 times higher than the upper limit of normal value.
* Hepatitis B surface antigen positive, hepatitis C antibody positive, treponema pallidum antibody positive or HIV antibody positive in serum virology examination.
* Patients who have been treated with any other investigational drug or participated in another interventional clinical trial within 3 months prior to screening.
* Patients complicated with malignant tumor or undergoing anti-tumor therapy.
* Patients have serious mental and psychological disorders, cognitive disorders and the existence of a history of mental illness.
* Patients have been alcohol abuse within 3 months prior to screening (drinking more than 14 units of alcohol per week (1 unit ≈360 mL beer or 45 mL 40% spirits or 150 mL wine)); Alcohol breath test positive at screening or admission.
* Patients who smoked more than 5 cigarettes a day during the 3 months prior to the study and were unwilling to stop smoking during the study period.
* Patients had been excessive drinking of tea , coffee or caffeinated beverages for a long time (more than 8 cups per day, 1 cup =250 mL); Or any food or beverage containing caffeine or xanthine (such as coffee, strong tea, chocolate, etc.) within 48 hours prior to initial administration.
* Patients have a history of drug or substance abuse, or a positive drug screening test.
* Women who are pregnant or breast-feeding or who plan to become pregnant or breast-feeding during the study period, or who have a positive pregnancy test at the screening stage or baseline.
* The investigator considers that the patient has any other medical or psychological conditions that may pose an undue risk to the subject or interfere with the subject's ability to comply with study protocol requirements or complete the study.

Primary outcomes:
measure: The number of any adverse events (AE)
timeFrame: 35 days after the last dose
measure: The number of serious adverse events (SAE)
timeFrame: 35 days after the last dose
Secondary outcomes:
measure: AUC 0-t (Area Under The Plasma Concentration Versus Time Curve)
timeFrame: 35 days after the last dose
measure: Cmax(Peak Plasma Concentration)
timeFrame: 35 days after the last dose
measure: AUC inf (Area Under The Plasma Concentration Versus Time Curve)
timeFrame: 35 days after the last dose
measure: Tmax(Peak Time)
timeFrame: 35 days after the last dose
measure: T ½(Terminal elimination half-life)
timeFrame: 35 days after the last dose
measure: CL(Clearance Rate)
timeFrame: 35 days after the last dose
measure: The uric acid to creatinine ratio in Urine
timeFrame: 35 days after the last dose
measure: Vd(Apparent volume of distribution)
timeFrame: 35 days after the last dose
measure: λz
timeFrame: 35 days after the last dose
measure: The positive rate of anti-uricase antibody
timeFrame: 35 days after the last dose
measure: The positive rate of anti-PEG antibody
timeFrame: 35 days after the last dose
measure: The positive rate of anti-PEG-uricase antibody
timeFrame: 35 days after the last dose
measure: Antibody titer of anti-uricase antibody
timeFrame: 35 days after the last dose
measure: Antibody titer of anti-PEG Antibody
timeFrame: 35 days after the last dose
measure: Antibody titer of anti-PEG-uricase Antibody
timeFrame: 35 days after the last dose
measure: Positive rate of neutralizing antibody(NAb)
timeFrame: 35 days after the last dose
Other outcomes:
measure: pUox(Plasma uricase activity)
timeFrame: 35 days after the last dose
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of Bengbu medical college
state: Anhui
Study officials:
affiliation: Shanghai Institute Of Biological Products
name: The First Affiliated Hospital of Bengbu Medical College The First Affiliated Hospital of Bengbu Medical College, Master
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital of Bengbu Medical University
name: Huan Zhou
role: PRINCIPAL_INVESTIGATOR
References: