Study to Evaluate HZN-457 in Healthy Volunteers

A Phase 1 Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HZN-457 in Healthy Volunteers

The purpose of this first in human study is to assess safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single ascending doses of HZN-457.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: HZN-457; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • New Zealand Clinical Research
  • Christchurch, New Zealand
    • New Zealand Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Screening serum uric acid (sUA) ≥ 4 mg/dL (238 µmol/L)
• Screening body mass index (BMI) between 20 to 34.0 kg/m2, inclusive
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG findings, as deemed by the Investigator.
• Male participants must refrain from donating sperm and either agree to remain abstinent from heterosexual intercourse OR agree to utilize contraception
• Female participants must be non-pregnant, non-lactating postmenopausal woman of non-childbearing potential (WONCBP) with a follicle-stimulating hormone (FSH) level in the postmenopausal range (> 40 IU/L)

Exclusion Criteria:

• History or presence of gout.
• Use of any prescription medication within 14 days or 5 half-lives prior to dosing
• Participation in another investigational clinical study (eg, drug, vaccine, invasive device) within 30 days or 5 half-lives, whichever is longer, prior to Day 1.
• Current liver disease, as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels > upper limit of normal (ULN) at Screening or Day -1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo will be given in one subcutaneous administration
Experimental: HZN-457	Drug: HZN-457; HZN-457 will be given in one subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) (injection site reactions (ISRs).	Day 1 up to Day 337
Change from Baseline in Hemoglobin value.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in white blood cell counts.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in platelet counts.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Prothrombin Time.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Activated Partial Thromboplastin Time.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Aspartate Aminotransferase (AST) value.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Alanine Aminotransferase (ALT) value.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Urinalysis values.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Systolic Blood Pressure values.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Diastolic Blood Pressure values.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Pulse Rate values.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Respiratory Rate values.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Body Temperature values.	Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in ECG Heart Rate values.	Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in ECG PR values.	Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in ECG QRS values.	Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in ECG QT values.	Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in ECG QTc values.	Baseline, Day 1 Post-Dose, Day 2, Day 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak plasma concentration (Cmax)	Day 1 to Day 8
Time to peak plasma concentration (Tmax)	Day 1 to Day 8
Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)	Day 1 to Day 8
Elimination half-life (t1/2)	Day 1 to Day 8
Fraction of the administered dose excreted into the urine (Fe)	Day 1 to Day 2
Change and percent change from baseline in serum uric acid (sUA) evaluated post dosing	Day 1 to Day 337

Collaborators and Investigators

• Sponsor: Horizon Therapeutics Ireland DAC
• Investigators: Study Director: Horizon Medical Director, Horizon Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Actual): August 9, 2023
• Study Completion (Actual): August 9, 2023

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: HZNP-HZN-457-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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