An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc)

Study Overview
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Brief Summary
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Primary Objectives: The primary efficacy objective is to assess the efficacy of 52 weeks of open-label treatment with HZN-825 in participants with diffuse cutaneous systemic sclerosis, as measured by change from both baselines in forced vital capacity percent (FVC %) predicted. The primary safety objective is to examine the safety and tolerability of 52 weeks of open-label treatment with HZN-825, inclusive of, but not limited to, adverse events (AEs), serious AEs (SAEs) and the adverse event of special interest (AESI), from Day 1 to 4 weeks after last dose.

Detailed Description
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This is an open-label, repeat-dose, multicenter extension trial of HZNP-HZN-825-301. Participants who complete the double-blind Treatment Period (Week 52) in Trial HZNP-HZN-825-301 will be eligible to enter this 52-week extension trial. Participants entering this extension trial will complete the Week 52 Visit activities in HZNP-HZN-825-301 and will not complete the Safety Follow-up Visit 4 weeks after the last dose of trial drug in HZNP-HZN-825-301.

Official Title
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A Multicenter, Open-label Extension Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis

Conditions
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Diffuse Cutaneous Systemic Sclerosis, Sclerosis, Systemic

Intervention / Treatment
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* Drug: HZN-825


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 1. Completed the double-blind Treatment Period (Week 52) in Trial HZNP-HZN-825-301; participants prematurely discontinued from trial drug in Trial HZNP-HZN-825-301 for reasons other than safety or toxicity can be included at the discretion of the Investigator after completing Trial HZNP-HZN-825-301 scheduled visits, including Week 52 assessments. Key Exclusion Criteria: Anticipated use of another investigational agent for any condition during the course of the trial. New diagnosis of malignant condition after enrolling in Trial HZNP-HZN-825-301 (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). Women of childbearing potential (WOCBP) or male participants not agreeing to use highly effective method(s) of birth control throughout the trial and for 4 weeks after last dose of trial drug as defined in the protocol. Any new development with the participant's disease or condition or any significant laboratory test abnormality during the course of Trial HZNP-HZN-825-301 that, in the opinion of the Investigator, would potentially put the subject at unacceptable risk. Pregnant or lactating women. Participants will be ineligible if, in the opinion of the Investigator, they are unlikely to comply with the trial protocol or have a concomitant disease or condition that could interfere with the conduct of the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HZN-825<br>HZN-825 will be administered by mouth (PO) twice daily (BID) for 52 weeks | Drug: HZN-825<br>* HZN-825 will be administered BID for 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from trial baseline, defined as the latest measurement prior to the first dose of HZN-825 in FVC % predicted | As measured by a pulmonary function test called a spirometry. | Baseline to Week 52 | 
| Change from HZN-825 Baseline, defined as the latest measurement prior to the first dose of HZN-825 in either trial HZNP-HZN-825-301 or this extension trial in FVC % predicted | As measured by a pulmonary function test called a spirometry. | Baseline to Week 52 | 
| Incidence of treatment emergent adverse events (TEAEs) |  | Day 1 to Week 56 | 
| Incidence of adverse events of special interest (AESI) orthostatic hypotension |  | Day 1 to Week 52 | 
| Incidence and frequency of use of concomitant medication |  | Day 1 to Week 56 | 
| Change from trial baseline in vital signs as reported as TEAEs |  | Day 1 to Week 56 | 
| Change from HZN-825 baseline in vital signs as reported as TEAEs |  | Day 1 to Week 56 | 
| Change from trial baseline in abnormal and clinically significant 12-lead electrocardiogram (ECG) measurements. | Clinically significant changes in ECGs is defined as any clinical significant difference in heart rate, RR interval, PR interval, QRS, and QT interval corrected using Fridericia's formula (QTcF). | Baseline to Week 52 | 
| Change from HZN-825 trial baseline in abnormal and clinically significant 12-lead ECG measurements. | Clinically significant changes in ECGs is defined as any clinical significant difference in heart rate, RR interval, PR interval, QRS, and QT interval corrected using Fridericia's formula (QTcF). | Baseline to Week 52 | 
| Change from trial baseline in abnormal laboratory test results | Clinically significant lab values in serum chemistry, hematology, lipids, coagulation tests and urinalyses will be assessed (including Grade 3 or higher per common terminology criteria for adverse events) | Day 1 to Week 56 | 
| Change from HZN-825 baseline in abnormal laboratory test results | Clinically significant lab values in serum chemistry, hematology, lipids, coagulation tests and urinalyses will be assessed (including Grade 3 or higher per common terminology criteria for adverse events) | Day 1 to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scleroderma, Forced vital capacity