NCT04781543终止2 期
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
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 301
- 试验地点
- 4
- 主要终点
- Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52
研究概览
简要总结
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.
详细描述
Acquired from Horizon in 2024.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
- •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.
- •Pregnant or lactating women.
- •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.
- •Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.
- •Known history of positive test for human immunodeficiency virus (HIV). HIV testing is optional based on Investigator assessment, institutional practices or local guidelines to rule out suspected HIV or potential for a positive HIV result. Subject consent is required prior to HIV testing.
- •Active hepatitis (hepatitis B: positive hepatitis B surface antigen and positive anti-hepatitis B core antibody [anti-HBcAb] and negative hepatitis B surface antibody [HBsAb] or positive for HBcAb with a positive test for HBsAb and with presence of hepatitis B virus DNA at Screening; hepatitis C: positive anti-hepatitis C virus [anti-HCV] and positive RNA HCV).
- •Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.
- •Previous organ transplant (including allogeneic and autologous marrow transplant).
- •International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.
- •Alanine aminotransferase or aspartate aminotransferase >2 × ULN.
- •Estimated glomerular filtration rate <30 mL/min/1.73 m^2 at Screening.
- •Total bilirubin >2 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL.
- •Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.
研究组 & 干预措施
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.
干预措施: HZN-825 QD (Drug)
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.
干预措施: HZN-825 BID (Drug)
Placebo
Placebo Comparator
One set of 2 placebo tablets in the morning and one set of 2 placebo tablets in the evening.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52
时间窗: Baseline and 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.
次要结局
- 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)
- Change From Baseline in the Physical Effects Subscale of the Scleroderma Skin Patient-reported Outcome (SSPRO-18) at Week 52(Baseline and Week 52)
- Change From Baseline in the Physical Limitations Subscale of the SSPRO-18 at Week 52(Baseline and Week 52)
- Number of Participants With an mRSS Decrease of ≥ 5 Points and 25% From Baseline at Week 52(Baseline and Week 52)
- Number of Participants Who Were Responders at Week 52(Week 52)
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)(From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months)
- Number of Participants Who Received Concomitant Medication(From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months)
- Pre- and Post-dose Plasma Concentrations of Fipaxalparant(Day 1 (post-dose), Week 4 (pre-dose), Week 10 (anytime at the visit), Weeks 16 and 28 (pre-dose and post-dose) and Weeks 40 and 52 (pre-dose))
研究者
研究点 (4)
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