A Study Exploring Efficacy of Pegloticase in Subjects With Asymptomatic Hyperuricemia

NCT ID: NCT05302388

Last Updated: 2023-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-11
• Study Completion Date: 2023-01-09

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.

Conditions

Asymptomatic Hyperuricemia

Keywords

Hyperuricemia; Pegloticase; Safety; Tolerability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental group

Drug: SIBP-R002 \& Dexamethasone/Methyl prednisolone \& Diphenhydramine Starting from the lowest dose, when the former dose does not meet the termination criteria, then start the next dose group study until Maximum Tolerated Dose (MTD).

Group Type: EXPERIMENTAL

SIBP-R002

Intervention Type: DRUG

SIBP-R002: injection; strength: 1, 2, 4, 8 or 12 mg; dose escalation and the first group is 1mg (intravenous infusion, 5 groups, the first group consisted of four people, and the other groups consisted of eight).

Dexamethasone or Methyl prednisolone

Intervention Type: DRUG

Intravenous infusion, 5mg or 1\~2mg/kg. These were administered within 30 minutes prior to infusion of the experimental drug.

Diphenhydramine

Intervention Type: DRUG

10mg, intramuscular injection.These were administered within 30 minutes prior to infusion of the experimental drug.

Placebo control group

Placebo control: The same volume of placebo as SIBP-R002 \& Dexamethasone/Methyl prednisolone \& Diphenhydramine The rule and dose of placebo were the same as SIBP-R002.

Group Type: PLACEBO_COMPARATOR

Dexamethasone or Methyl prednisolone

Intervention Type: DRUG

Intravenous infusion, 5mg or 1\~2mg/kg. These were administered within 30 minutes prior to infusion of the experimental drug.

Diphenhydramine

Intervention Type: DRUG

10mg, intramuscular injection.These were administered within 30 minutes prior to infusion of the experimental drug.

Placebo

Intervention Type: DRUG

The same volume of placebo as SIBP-R002: injection; strength: the same volume of placebo as SIBP-R002 of 1, 2, 4, 8 or 12 mg (intravenous infusion, 5 groups, the first group consisted of one people, and the other groups consisted of two). The rule and dose of placebo were the same as SIBP-R002.

Interventions

SIBP-R002

SIBP-R002: injection; strength: 1, 2, 4, 8 or 12 mg; dose escalation and the first group is 1mg (intravenous infusion, 5 groups, the first group consisted of four people, and the other groups consisted of eight).

Intervention Type: DRUG

Dexamethasone or Methyl prednisolone

Intravenous infusion, 5mg or 1\~2mg/kg. These were administered within 30 minutes prior to infusion of the experimental drug.

Intervention Type: DRUG

Diphenhydramine

10mg, intramuscular injection.These were administered within 30 minutes prior to infusion of the experimental drug.

Intervention Type: DRUG

Placebo

The same volume of placebo as SIBP-R002: injection; strength: the same volume of placebo as SIBP-R002 of 1, 2, 4, 8 or 12 mg (intravenous infusion, 5 groups, the first group consisted of one people, and the other groups consisted of two). The rule and dose of placebo were the same as SIBP-R002.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Bengbu Medical University

OTHER

Sponsor Role: collaborator

Shanghai Institute Of Biological Products

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

The First Affiliated Hospital of Bengbu Medical College The First Affiliated Hospital of Bengbu Medical College, Master

Role: STUDY_DIRECTOR

Shanghai Institute Of Biological Products

Huan Zhou

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Bengbu Medical University

Locations

The first affiliated hospital of Bengbu medical college

Bengbu, Anhui, China

Countries

China

Other Identifiers

SIBP-R002

Identifier Type: -

Identifier Source: org_study_id