A Study Exploring Efficacy of Pegloticase in Subjects With Asymptomatic Hyperuricemia

NCT05302388 | Completed Phase 1 DMC

• 1 other identifier: SIBP-R002
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Asymptomatic Hyperuricemia

Keywords

Hyperuricemia; Pegloticase; Safety; Tolerability

Outcome Measures

Primary Outcomes (2)

• The number of any adverse events (AE)

  All subjects were observed during the trial for any AE that occurred during the clinical study, including clinical symptoms and life abnormal physical signs, abnormalities in electrocardiogram and laboratory tests. Attention should be paid to the occurrence of AE related to infusion reaction, allergic reaction, vomiting and watery stools/loose stools, acute attack of gout, cardiovascular adverse events and so on.

  35 days after the last dose

• The number of serious adverse events (SAE)

  That is serious adverse events, any serious adverse events that occurred to the subject during the study period.

  35 days after the last dose

Secondary Outcomes (16)

• AUC 0-t (Area Under The Plasma Concentration Versus Time Curve)

  35 days after the last dose

• Cmax(Peak Plasma Concentration)

  35 days after the last dose

• AUC inf (Area Under The Plasma Concentration Versus Time Curve)

  35 days after the last dose

• Tmax(Peak Time)

  35 days after the last dose

• T ½(Terminal elimination half-life)

  35 days after the last dose

Other Outcomes (1)

• pUox(Plasma uricase activity)

  35 days after the last dose

Study Arms (2)

Experimental group

EXPERIMENTAL

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).

Drug: SIBP-R002; Drug: Dexamethasone or Methyl prednisolone; Drug: Diphenhydramine

Placebo control group

PLACEBO COMPARATOR

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.

Drug: Dexamethasone or Methyl prednisolone; Drug: Diphenhydramine; Drug: Placebo

Interventions

SIBP-R002 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).

Experimental group

Dexamethasone or Methyl prednisolone DRUG

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

Experimental group; Placebo control group

Diphenhydramine DRUG

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

Experimental group; Placebo control group

Placebo 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.

Placebo control group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Institute Of Biological Products: lead
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Study Sites (1)

The first affiliated hospital of Bengbu medical college

Bengbu, Anhui, China

Location

MeSH Terms

Conditions

Hyperuricemia

Interventions

Dexamethasone; Diphenhydramine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

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

  Shanghai Institute Of Biological Products

  STUDY DIRECTOR

• Huan Zhou

  The First Affiliated Hospital of Bengbu Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the study period, the subjects and all personnel involved in the evaluation and analysis of the results were unaware of the actual grouping.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a phase I randomized, double-blind, placebo-controlled and dose-increasing single dosing study.

Study Record Dates

• First Submitted: March 19, 2022
• First Posted: March 31, 2022
• Study Start: April 11, 2022
• Primary Completion: January 9, 2023
• Study Completion: January 9, 2023
• Last Updated: December 27, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)