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

NCT04781543 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: HZNP-HZN-825-3012020-005764-62
• Study Type: interventional
• Target: 301
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial. Participants will be screened within 6 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio to receive HZN-825 300 mg QD, HZN-825 300 mg BID or placebo for 52 weeks. The trial will include up to a 42-day Screening Period and a 52-week Double-blind Treatment Period. Participants will take their first dose of trial drug at the clinic and will participate in trial visits at Week 4 and every 6 weeks thereafter until Week 52. All participants who complete the Double-blind Treatment Period (Week 52) will be eligible to enter a 52-week extension trial (HZNP-HZN-825-302, NCT05626751). Participants not entering the extension trial will participate in a Safety Follow-up Visit 4 weeks after the last dose of trial drug.

Conditions

Diffuse Cutaneous Systemic Sclerosis; Sclerosis, Systemic

Keywords

Scleroderma

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52

  FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria with a maximum of 8 maneuvers. 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

Secondary Outcomes (12)

• Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52

  Baseline and Week 52

• Number of Participants Responding to Treatment Based on the Revised Composite Response Index in Systemic Sclerosis (CRISS 25) at Week 52

  Baseline to Week 52

• Change From Baseline in HAQ-DI at Week 52

  Baseline and Week 52

• Change From Baseline in CGA at Week 52

  Baseline and Week 52

• Change From Baseline in PTGA at Week 52

  Baseline and Week 52

Study Arms (3)

HZN-825 300 mg once daily (QD)

EXPERIMENTAL

One set of 2 HZN-825 150mg tablets in the morning and one set of 2 placebo tablets in the evening.

Drug: HZN-825 QD

HZN-825 300 mg twice daily (BID)

EXPERIMENTAL

One set of 2 HZN-825 150mg tablets in the morning and one set of 2 HZN-825 150mg tablets in the evening.

Drug: HZN-825 BID

Placebo

PLACEBO COMPARATOR

One set of 2 placebo tablets in the morning and one set of 2 placebo tablets in the evening.

Drug: Placebo

Interventions

HZN-825 QD DRUG

300 mg oral tablets QD

HZN-825 300 mg once daily (QD)

HZN-825 BID DRUG

300 mg oral tablets BID

HZN-825 300 mg twice daily (BID)

Placebo DRUG

Placebo BID

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Male or female between the ages of 18 and 75 years, inclusive, at Screening.
• Meets the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc with a total score of ≥9 (Van den Hoogen et al., 2013).
• Classified as having skin involvement proximal to the elbow and knee (diffuse cutaneous SSc subset by LeRoy and Medsger, 2001).
• At the time of enrollment, less than or equal to 72 months (6 years) since the onset of the first SSc manifestation, other than Raynaud's phenomenon.
• Skin thickening from SSc in the forearm suitable for repeat biopsy.
• mRSS units ≥15 at Screening.
• FVC ≥45% predicted at Screening, as determined by spirometry.
• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

You may not qualify if:

• Positive for anti-centromere antibodies with the exception that subjects who are positive for both anti-centromere and anti-topoisomerase 1 antibodies may be enrolled.
• Diagnosed with sine scleroderma or limited cutaneous SSc.
• Diagnosed with other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren's syndrome.
• Scleroderma renal crisis diagnosed within 6 months of the Screening Visit.
• Any of the following cardiovascular diseases:
• uncontrolled, severe hypertension (≥160/100 mmHg) or persistent low blood pressure (systolic blood pressure \<90 mmHg) within 6 months of Screening,
• myocardial infarction within 6 months of Screening,
• unstable cardiac angina within 6 months of Screening.
• DLCO \<40% predicted (corrected for hemoglobin). If severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure is of clinical concern for any subject, consider using a DLCO up to 6 months before the Screening Visit.
• Pulmonary arterial hypertension (PAH) by right heart catheterization requiring treatment with more than 1 oral PAH-approved therapy or any parenteral therapy. Treatment is allowed for erectile dysfunction and/or Raynaud's phenomenon/digital ulcers.
• Corticosteroid use for conditions other than SSc within 4 weeks prior to Screening (topical steroids for dermatological conditions and inhaled/intranasal/intra-articular steroids are allowed).
• Use of any other non-steroid immunosuppressive agent, small biologic molecule, cytotoxic or anti-fibrotic drug within 4 weeks of Screening, including cyclophosphamide, azathioprine (Imuran®) or other immunosuppressive or cytotoxic medication. Exceptions include mycophenolate mofetil (CellCept®), mycophenolic acid (Myfortic®), methotrexate and low-dose prednisone, as follows: use of CellCept ≤3 g/day, Myfortic ≤2.14 g/day, methotrexate ≤20 mg/week and prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. Subjects taking CellCept, Myfortic or methotrexate must have been doing so for ≥6 months and the dose must have been stable for ≥4 weeks prior to the Day 1 Visit. Prednisone must have been at a stable dose for ≥8 weeks prior to the Day 1 Visit. It is acceptable to be on background low-dose prednisone and anti-malarial drug along with CellCept, Myfortic or methotrexate. Rituximab must not have been used within 6 months of the Day 1 Visit.
• Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed) at the time of randomization.
• Use of a United States Food and Drug Administration-approved agent for SSc or an investigational agent for any condition within 90 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
• Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).

Sponsors & Collaborators

• Amgen: lead

Study Sites (4)

Institute of Rheumatology - PPDS

Belgrade, 11000, Serbia

Location

Military Medical Academy

Belgrade, 11000, Serbia

Location

Institute for Treatment and Rehabilitation Niska Banja

Niška Banja, 708120, Serbia

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Scleroderma, Diffuse; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 4, 2021
• Study Start: November 5, 2021
• Primary Completion: February 24, 2025
• Study Completion: February 24, 2025
• Last Updated: March 20, 2026
• Results First Posted: March 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

SE (3); ES (1)