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

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

Primary Objectives:

1. 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.
2. 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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diffuse Cutaneous Systemic Sclerosis; Sclerosis, Systemic
• Intervention / Treatment: Drug: HZN-825

Detailed Description

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.

Acquired from Horizon in 2024.

• Study Type: Interventional
• Enrollment (Estimated): 246
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Mendoza, Argentina, M5500CPH
    • I.R. Medical Center - Hospital de Dia
  • Buenos Aires
    • Cuiudad Autónoma De, Buenos Aires, Argentina, C1430EGF
      • Clinica Adventista Belgrano
    • La Plata, Buenos Aires, Argentina, B1900
      • Framingham Centro Medico
  • Ciudad Autónoma De BuenosAires
    • Ciudad Autónoma de Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina, C1406AGA
      • Aprillus Asistencia e Investigacion de Arcis Salud SRL
  • Tucumán
    • San Miguel De Tucumán, Tucumán, Argentina, T4000AXL
      • Centro de Investigaciones Medicas Tucuman
    • San Miguel De Tucumán, Tucumán, Argentina, T4000AXL
      • Centro de Investigaciones Reumatologicas
    • San Miguel De Tucumán, Tucumán, Argentina, T4000IHE
      • Clinica Mayo de U.M.C.B. S.R.L
• France
  • Paris, France, 75014
    • Hôpital Cochin
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
• Greece
  • Thessaloniki, Greece, 546 36
    • Kianous Stavros
  • Thessaloniki, Greece, 546 42
    • Ippokratio General Hospital of Thessaloniki
• Israel
  • Tel-Aviv
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 64239
      • Tel Aviv Sourasky Medical Center - PPDS
• Japan
  • Saitama
    • Iruma-Gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Seoul, Korea, Republic of, 4763
    • Hanyang University Medical Center
• Mexico
  • Guadalajara, Mexico, 44600
    • Clinica de Investigacion en Reumatologia y Obesidad
  • Merida, Mexico, 97000
    • Unidad de Atencion Medica e Investigacion en Salud
  • Mexico, Mexico, 6700
    • CITER, Centro de Investigacion y Tratamiento de las Enfermedades Reumaticas SA de CV
  • Distrito Federal
    • San Miguel Chapultepec, Distrito Federal, Mexico, 11850
      • Centro de Investigación y Tratamiento Reumatológico S.C
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44690
      • Centro de Estudios de Investigacion Basica Y Clinica SC
    • Guadalajara, Jalisco, Mexico, ZC 44160
      • Centro Integral Reumatologia SA de CV
  • San Luis Potosí
    • Burocratas Del Estado, San Luis Potosí, Mexico, 78213
      • Centro de Alta Especialidad En Reumatologia E Investigacion Del Potosi SC
• Spain
  • Sevilla, Spain, 41010
    • Hospital Quironsalud Infanta Luisa
• United States
  • Florida
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Clinical Research, LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • Michigan Medicine University of Michigan
  • South Carolina
    • Charleston, South Carolina, United States, 29425-8900
      • Medical University of South Carolina - PPDS
  • Texas
    • Dallas, Texas, United States, 75231-4345
      • Metroplex Clinical Research Center
    • Houston, Texas, United States, 77030
      • UT Physicians Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Anticipated use of another investigational agent for any condition during the course of the trial.
2. 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).
3. 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.
4. 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.
5. Pregnant or lactating women.
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Scleroderma; Forced vital capacity
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: HZNP-HZN-825-302; 2021-006271-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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