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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

1.Written informed consent.
2.Male or female between the ages of 18 and 75 years, inclusive, atScreening.
3.Meets the 2013 American College of Rheumatology/European LeagueAgainst Rheumatism classification criteria for SSc with a total score of =9 (Van den Hoogen et al., 2013).
4.Classified as having skin involvement proximal to the elbow and/or knee(diffuse cutaneous SSc subset by LeRoy and Medsger, 2001).
5.At the time of enrollment, less than or equal to 72 months (6 years) since the onset of thefirst SSc manifestation, other than Raynaud's phenomenon.
6.Skin in the forearm suitable for repeat biopsy (only applicable to the first 110 subjects for whom biopsy will be performed).
7.mRSS units =15 at Screening.8.FVC =45% predicted at Screening, as determined by spirometry.9.Willing and able to comply with the prescribed treatment protocoland evaluations for the duration of the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1.Positive for anti-centromere antibodies with the exception that subjects who are positive for both anti-centromere and antitopoisomerase 1 antibodies may be enrolled.
2.Diagnosed w/sine scleroderma or limited cutaneous SSc.
3.Diagnosed w/other autoimmune connective tissue diseases ,except forfibromyalgia, scleroderma-associated myopathy & secondarySjogren's syndrome.
4.Scleroderma renal crisis diagnosed within6months of the Screening Visit.
5.Any of the following cardiovascular diseases: a. uncontrolled, severe hypertension(=160/100mmHg)or persistent low blood pressure (systolic blood pressure<90 mmHg)within6months of Screening, b. myocardial infarction within6months of Screening, c. unstable cardiac angina within6months of Screening.
6.DLCO<40%predicted(corrected for hemoglobin).If severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) exposure is of clinical concern for any subject, consider using a DLCO up to6months before the Screening Visit.
7.Pulmonary arterial hypertension(PAH)by right heart catheterization requiring treatment w/more than1oral PAH-approved therapy or any parenteral therapy. Treatment is allowed for erectile dysfunction and/or Raynaud's phenomenon/digital ulcers.
8.Corticosteroid use for conditions other than SSc within4weeks prior to Screening(topical steroids for dermatological conditions& inhaled/intranasal/intra-articular steroids are allowed).
9.Use of any other non-steroid immunosuppressive agent, small biologic molecule, cytotoxic or antifibrotic drug within4weeks prior to 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 =3g/day, Myfortic =2.14g/day, methotrexate =20 mg/week and prednisone =10 mg/day (or equivalent dosing of glucocorticoids) is allowed. See Table 9.1 for full details. Subjects taking CellCept, Myforticor methotrexate must have been doing so for=6months 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 Day1Visit. It is acceptable to be on background low-dose prednisone &anti-malarial drug along with CellCept, Myfortic or methotrexate. Rituximab must not have been used within 6 months of the Day1Visit.Subjects must not be withdrawn from any standard-of-care treatment that is considered necessary for the clinical management of the subject in order to fulfill the trial eligibility requirements.
10.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.
11.Use of a United States Food and Drug Administration-approved agent for SSc or an investigational agent for any condition within 90days or 5half-lives,whichever is longer, prior to Screening or anticipated use during the course of the trial.
12.Malignant condition in the past5years(except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
13.Women of childbearing potential (WOCBP) or male subjects not agreeing to use highly effective method(s)of birth control throughout the trial and for 4 weeks after last dose of trial drug. Male subjects must refrain from sperm donation and females from egg/ova donation for this same time period. Women are consi

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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