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

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 300

Inclusion Criteria

1.Written informed consent.
2.Male or female between the ages of 18 and 75 years, inclusive, at
Screening.
3.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).
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 36 months since the onset of the
first SSc manifestation, other than Raynaud's phenomenon.
6.Skin thickening from SSc in the forearm suitable for repeat biopsy.
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 protocol
and 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.
2.Diagnosed with sine scleroderma or limited cutaneous SSc.
3.Diagnosed with other autoimmune connective tissue diseases, except
for fibromyalgia, scleroderma-associated myopathy and secondary
Sjogren's syndrome.
4.Scleroderma renal crisis diagnosed within 6 months of the Screening
Visit.
5.Any of the following cardiovascular diseases:
a.uncontrolled, severe hypertension (=160/100 mmHg) or persistent
low blood pressure (systolic blood pressure <90 mmHg) within 6 months
of Screening,
b.myocardial infarction within 6 months of Screening,
c.unstable cardiac angina within 6 months 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 to 6 months before the
Screening Visit.
7.Pulmonary arterial hypertension (PAH) by right heart catheterization
requiring treatment with more than1 oral 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 within 4 weeks prior
to Screening (topical steroids for dermatological conditions and
inhaled/intranasal/intra-articular steroids are allowed).
9.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.
10.Known active bacterial, viral, fungal, mycobacterial or other infection,
including tuberculosis or atypical mycobacterial disease (fungal
infections of nail beds are allowed).
11.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.
12.Malignant condition in the past 5 years (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 1 month 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 considered of childbearing potential if they are not postmenopausal and not surgically sterile (documented bilateral salpingectomy, bilateral oophorectomy, or hysterectomy). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
14.Pregnant or lactating women.
15.Current drug or alcohol abuse or history of either within the previous
2 years, in the opinion of the Investigator or as reported by the subject.
16.Previous enrollment in this trial or participation in a prior HZN-825 or
SAR100842 clinical trial.
17.Known history of positive test for human immunodeficiency virus.
18.Active hepatitis (hepatitis B: positive hepatit

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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