Study to Evaluate HZN-457 in Healthy Volunteers

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

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: HZN-457
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HZN-457<br> | Drug: HZN-457<br>* HZN-457 will be given in one subcutaneous administration<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo will be given in one subcutaneous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |