Clinical trial NCT05565768: Study to Evaluate HZN-457 in Healthy Volunteers
Official title: A Phase 1 Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HZN-457 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland
Sponsor class: INDUSTRY
First posted: 2022-10-04
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) (injection site reactions (ISRs).
timeFrame: Day 1 up to Day 337
measure: Change from Baseline in Hemoglobin value.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in white blood cell counts.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in platelet counts.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Prothrombin Time.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Activated Partial Thromboplastin Time.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Aspartate Aminotransferase (AST) value.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Alanine Aminotransferase (ALT) value.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Urinalysis values.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Systolic Blood Pressure values.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Diastolic Blood Pressure values.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Pulse Rate values.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Respiratory Rate values.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in Body Temperature values.
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
measure: Change from Baseline in ECG Heart Rate values.
timeFrame: Baseline, Day 1 Post-Dose, Day 2, Day 4
measure: Change from Baseline in ECG PR values.
timeFrame: Baseline, Day 1 Post-Dose, Day 2, Day 4
measure: Change from Baseline in ECG QRS values.
timeFrame: Baseline, Day 1 Post-Dose, Day 2, Day 4
measure: Change from Baseline in ECG QT values.
timeFrame: Baseline, Day 1 Post-Dose, Day 2, Day 4
measure: Change from Baseline in ECG QTc values.
timeFrame: Baseline, Day 1 Post-Dose, Day 2, Day 4
Secondary outcomes:
measure: Peak plasma concentration (Cmax)
timeFrame: Day 1 to Day 8
measure: Time to peak plasma concentration (Tmax)
timeFrame: Day 1 to Day 8
measure: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)
timeFrame: Day 1 to Day 8
measure: Elimination half-life (t1/2)
timeFrame: Day 1 to Day 8
measure: Fraction of the administered dose excreted into the urine (Fe)
timeFrame: Day 1 to Day 2
measure: Change and percent change from baseline in serum uric acid (sUA) evaluated post dosing
timeFrame: Day 1 to Day 337
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
Study officials:
affiliation: Horizon Therapeutics
name: Horizon Medical Director
role: STUDY_DIRECTOR
References: