A Randomized, Double-blind, Placebo-controlled, Repeat-dose, Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients with Diffuse Cutaneous Systemic Sclerosis
- Conditions
- Diffuse Cutaneous Systemic Sclerosis10003816Disease characterized by skin hardening (fibrosis) and problems in many organs of the body
- Registration Number
- NL-OMON49927
- Lead Sponsor
- Horizon Therapeutics Ireland DAC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 4
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.
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 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 t
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change in FVC % predicted from Baseline to Week 52</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Change from Baseline in HAQ-DI at Week 52.<br /><br>2. Change from Baseline in MDGA at Week 52.<br /><br>3. Change from Baseline in PTGA at Week 52.<br /><br>4. Change from Baseline in the Physical Effects subscale of the SSPRO-18 at<br /><br>Week 52.<br /><br>5. Change from Baseline in the Physical Limitations subscale of the SSPRO-18 at<br /><br>Week 52.<br /><br>6. Proportion of subjects with an mRSS decrease of >=5 points and 25% from<br /><br>Baseline at Week 52.<br /><br>7. Responder rate (defined as ACR-CRISS [predicted probability] of at least<br /><br>0.6) at Week 52.<br /><br>8. Proportion of subjects with an improvement in >=3 of 5 core measures from<br /><br>Baseline: >=20% in mRSS, >=20% in HAQ-DI, >=20% in PTGA, >=20% in MDGA and >=5% for<br /><br>FVC % predicted at Week 52 (ACR-CRISS-20).</p><br>