A Randomized, Double-blind, Placebo-controlled, Repeat-dose, Multicenter Trial of HZN-825 in Patients with Diffuse Cutaneous Systemic Sclerosis
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Registration Number
- JPRN-jRCT2031220221
- Lead Sponsor
- Sato Toshiyuki
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 21
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 equal to or more than 9.
4. Classified as having skin involvement proximal to the elbow and/or knee.
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 in the forearm suitable for repeat biopsy (only applicable to the first 110 subjects for whom biopsy will be performed).
7. mRSS units of equal to or more than 15 at Screening.
8. FVC of equal to or more than 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.
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 Sjogrens 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 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.
7. 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 Raynauds 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 prior to Screening, including cyclophosphamide, azathioprine (Imuran) or other immunosuppressive or cytotoxic medication. Avoiding the use of listed prohibited treatments must not be considered detrimental and must be indicated by the treating physician. Exceptions include mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic), methotrexate and low-dose prednisone, as follows: use of CellCept equal to or less than 3 g/day, Myfortic equal to or less than 2.14 g/day, methotrexate equal to or less than 15 mg/week and prednisone equal to or less than 10 mg/day (or equivalent dosing of glucocorticoids) is allowed. See Table 9.1 in the protocol for full details. Subjects taking CellCept, Myfortic or methotrexate must have been doing so for equal to or more than 6 months and the dose must have been stable for equal to or more than 16 weeks prior to the Day 1 Visit. Prednisone must have been at a stable dose for equal to or more than 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. 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).
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 me
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change in FVC % predicted from Baseline to Week 52.
- Secondary Outcome Measures
Name Time Method 1. Change from Baseline in HAQ-DI at Week 52.<br>2. Change from Baseline in MDGA at Week 52.<br>3. Change from Baseline in PTGA at Week 52.<br>4. Change from Baseline in the Physical Effects subscale of the SSPRO-18 at Week 52.<br>5. Change from Baseline in the Physical Limitations subscale of the SSPRO-18 at Week 52.<br>6. Proportion of subjects with an mRSS decrease of >=5 points and 25% from Baseline at Week 52.<br>7. Responder rate (defined as ACR-CRISS [predicted probability] of at least 0.6) at Week 52.<br>8. Proportion of subjects with an improvement in >=3 of 5 core measures from Baseline: >=20% in mRSS, >=20% in HAQ-DI, >=20% in PTGA, >=20% in MDGA and >=5% for FVC % predicted at Week 52 (ACR-CRISS-20).