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: Terminated
• 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 (Actual): 174
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1406AGA
    • Aprillus Asistencia e Investigacion de Arcis Salud SRL
  • Cuiudad Autónoma de Buenos Aires, Argentina, C1430EGF
    • Clinica Adventista Belgrano
  • Mendoza, Argentina, M5500CPH
    • I.R. Medical Center - Hospital de Dia
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1900
      • Framingham Centro Medico
  • Ciudad Autónoma de BuenosAires
    • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1426
      • Consultorio Médico Dra. Rivera
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000AXL
      • Centro de Investigaciones Médicas Tucumán - PPDS
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000AXL
      • Centro de Investigaciones Reumatológicas
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000IHE
      • Clínica Mayo de U.M.C.B. S.R.L
• Chile
  • Región-MetropolitanadeSantiago
    • Santiago, Región-MetropolitanadeSantiago, Chile, 7510047
      • Prosalud y Cia Ltda.
• Greece
  • Thessaloniki, Greece, 546 42
    • General Hospital of Thessaloniki ''Hippokratio''
  • Thessaloniki, Greece, 546 36
    • Euromedica Kianous Stavros
  • Attica
    • Athens, Attica, Greece, 115 27
      • Laiko General Hospital of Athens
• Israel
  • Haifa, Israel, 31096
    • Rambam Health Care Campus - PPDS
  • Petah Tikva, Israel, 4910000
    • Rabin Medical Center - PPDS
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 52621
      • The Chaim Sheba Medical Center - PPDS
    • Tel Aviv, Tel Aviv, Israel, 64239
      • Tel Aviv Sourasky Medical Center Ichilov - PPDS
• Italy
  • Friuli Venezia Giulia
    • Udine, Friuli Venezia Giulia, Italy, 33100
      • Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
• Japan
  • Hokkaidô
    • Sapporo, Hokkaidô, Japan, 060-8543
      • Sapporo Medical University Hospital
    • Sapporo, Hokkaidô, Japan, 060-848
      • Hokkaido University Hospital
  • Nagasaki
    • Nagasaki, Nagasaki, Japan, 852-8102
      • Nagasaki University Hospital
  • Saitama
    • Iruma-Gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Bunkyo-Ku, Tokyo, Japan, 113-8603
      • Nippon Medical School Hospital
  • Ôsaka
    • Takatsuki-Shi, Ôsaka, Japan, 569-8686
      • Osaka Medical and Pharmaceutical University Hospital
• Mexico
  • Guadalajara, Mexico, 44600
    • Clinica de Investigacion en Reumatologia y Obesidad
  • Mérida, Mexico, 97000
    • Unidad de Atención Médica e Investigación en Salud
  • México, Mexico, 6700
    • CITER, Centro de Investigacion y Tratamiento de las Enfermedades Reumaticas SA de CV
  • 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
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14000
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
    • San Miguel Chapultepec, Mexico City, Mexico, 11850
      • Centro de Investigación y Tratamiento Reumatológico S.C
  • San Luis Potosí
    • Burócratas Del Estado, San Luis Potosí, Mexico, 78213
      • Centro de Alta Especialidad En Reumatologia E Investigacion Del Potosi SC
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-149
      • Malopolskie Centrum Kliniczne
  • Lubusz Voivodeship
    • Nowa Sól, Lubusz Voivodeship, Poland, 67-100
      • Twoja Przychodnia NCM
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-874
      • Medicover Integrated Clinical Services sp. z o.o - MICS - PPDS
    • Warsaw, Masovian Voivodeship, Poland, 02-665
      • Centrum Medyczne Reuma Park NZOZ
• Portugal
  • Lisbon, Portugal, 1649-035
    • Hospital de Santa Maria-Avenida Prof. Egas Moniz - PPDS
• Romania
  • Brasov, Romania, 500283
    • Centrul Medical de Diagnostic si Tratament Ambulator NEOMED SRL
  • București
    • Bucharest, București, Romania, 011172
      • Sf.Maria Clinical Hospital
    • Bucharest, București, Romania, 20475
      • Dr I Cantacuzino Clinical Hospital
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology - PPDS
  • Niška Banja, Serbia, 708120
    • Institute for Treatment and Rehabilitation Niska Banja
• South Korea
  • Seoul, South Korea, 06273
    • Gangnam Severance Hospital, Yonsei University Health System
  • Gwangju Gwang'yeogsi
    • Gwangju, Gwangju Gwang'yeogsi, South Korea, 61469
      • Chonnam National University Hospital
  • Gyeonggido
    • Seongnam, Gyeonggido, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • Seongdong-gu, Seoul Teugbyeolsi, South Korea, 04763
      • Hanyang University Seoul Hospital
• Spain
  • A Coruña, Spain, 15006
    • Hospital Universitario A Coruña
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Seville, Spain, 41010
    • Hospital Quironsalud Infanta Luisa
  • Valencia, Spain, 46017
    • Hospital Universitario Doctor Peset
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
• United Kingdom
  • London, City of
    • London, London, City of, United Kingdom, NW3 2QG
      • Royal Free Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032-9306
      • Arizona Arthritis and Rheumatology Associates -4550 E Bell Rd
  • California
    • Los Angeles, California, United States, 90095-8344
      • UCLA Medical Center
  • Florida
    • Miami, Florida, United States, 33136-1005
      • University of Miami Miller School of Medicine
    • Plantation, Florida, United States, 33324-2736
      • IRIS Research and Development LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70115-3584
      • DelRicht Clinical Research, LLC - Internal - Covington - PPDS
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-2642
      • Boston University School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • Michigan Medicine University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Cancer Center - Rochester - PPDS
  • North Carolina
    • Durham, North Carolina, United States, 27710-3037
      • Duke University Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425-8900
      • Medical University of South Carolina (MUSC) - PPDS
  • Texas
    • Houston, Texas, United States, 77030-5400
      • 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 Baseline in Forced Vital Capacity Percentage (FVC%) Predicted at Week 52	FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry. FVC is a measure of respiratory function. FVC% predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.	Baseline and Week 52
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) was defined as any untoward medical occurrence in a trial participant who received an investigational product (IP), regardless of a causal relationship with treatment. An AE could be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of an IP. TEAEs were defined as events that began or worsened in severity on or after the first dose of treatment through 28 days after the last dose or the cutoff date for ongoing participants. Serious TEAEs were those that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability/incapacity, led to a congenital anomaly/birth defect, or were considered other important medical events. Clinically significant changes in vital signs, electrocardiograms (ECGs), and laboratory tests were included as TEAEs.	From 1st dose to last dose + 28 days; median (min, max) time on trial was 8.5 (1.0, 14.0) months
Number of Participants Who Experienced AEs of Special Interest (AESI)	The following AESI was identified for this trial: Orthostatic hypotension defined as a reduction of systolic blood pressure by ≥20 mmHg or reduction of diastolic blood pressure by ≥10 mmHg and associated with symptoms such as lightheadedness, blurred vision, weakness, fatigue, cognitive impairment, nausea, palpitations, tremulousness, headache, presyncope or syncope.	Day 1 and at Weeks 4, 28 and 52
Number of Participants Using Any Concomitant Medication	Concomitant medications were defined as any medication that was ongoing, had a start date on or after the first dose of the trial drug, or had a stop date on or after the first dose date.	From 1st dose to last dose + 28 days; median (min, max) time on trial was 8.5 (1.0, 14.0) months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Actual): February 24, 2025
• Study Completion (Actual): February 24, 2025

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): January 5, 2026
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Scleroderma; Forced vital capacity
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: HZNP-HZN-825-302; 2023-509783-23-00 (Ctis)

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