A Phase 4 Multicenter, Randomized, Open-label, Efficacy Assessor Blinded Study of Risankizumab Compared to Deucravacitinib for the Treatment of Adult Subjects With Moderate Plaque Psoriasis Who Are Candidates for Systemic Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 393
- 试验地点
- 142
- 主要终点
- Period A: Percentage of Participants Achieving 90% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 90)
研究概览
简要总结
Psoriasis is a long-term skin disease which causes red, itchy, scaly patches most commonly on the knees, elbows, scalp, and torso (chest, back, and abdomen). In participants with psoriasis, certain skin cells multiply much faster and the skin can develop rough patches that may be red or white with scales. There are many types of psoriasis, but plaque psoriasis is the most common. The exact cause of psoriasis is unknown, but researchers think it may be caused by the body's immune system not working properly.
This study is designed to enroll 336 participants 18 years of age and older with have been diagnosed with moderate chronic plaque psoriasis for at least 6 months prior to Baseline (Day 1) and who have not previously been treated with a biologic treatment (natural substance that is made by using living cells in a laboratory). This is a Phase 4, randomized, open-label, assessor blinded, active comparator study with 2 Parts. Phase 4 studies test treatments that have already been approved to treat patients with a condition or disease. This study is open-label, which means that both participants and study doctors know which study treatment is given to participants
Participants will be administered subcutaneous (SC) treatment of risankizumab every 12 weeks for up to 44 weeks or provided deucravacitinib oral tablets to be taken once daily.
There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular (weekly, monthly) visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant with a diagnosis of chronic plaque psoriasis (PsO) with or without psoriatic arthritis, for at least 6 months prior to Baseline.
- •Stable moderate chronic plaque psoriasis at both Screening and Baseline as defined as:
- •Body Surface Area (BSA) ≥ 10% and ≤ 15%,
- •Psoriasis Area and Severity Index (PASI) ≥ 12, and
- •Static Physician Global Assessment (sPGA) = 3 (moderate) based on a 5-point scale (0 to 4).
- •Participant must be a candidate for systemic therapy as assessed by the investigator
- •Psoriasis inadequately controlled by topicals, phototherapy and/or systemic treatments (including, but not limited to, methotrexate, apremilast, cyclosporine A, corticosteroids, and/or cyclophosphamide)
排除标准
- •Participants with any form of PsO other than chronic plaque PsO (e.g., pustular PsO, palmoplantar pustulosis, acrodermatitis of Hallopeau, erythrodermic, or guttate PsO).
- •Participants with a history of current drug-induced PsO or a drug-induced exacerbation of preexisting PsO.
- •Participants with a history of active ongoing inflammatory skin diseases other than PsO (with or without PsA) that could interfere with the assessment of PsO (e.g., hyperkeratotic eczema).
- •Participants with a history of severe renal insufficiency defined as creatinine clearance < 30 mL/min and/or requiring hemodialysis or peritoneal dialysis.
- •Participantswith a history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.
- •Participants with a history of an allergic reaction or significant sensitivity to constituents of the study drugs (and its excipients) and/or other products in the same class.
- •Participants who have had major surgery performed within 12 weeks prior to randomization or planned during the conduct of the study (e.g., hip replacement, aneurysm removal, stomach ligation).
- •Participants with evidence of:
- •Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as:
- •HBV: Hepatitis B surface antigen (HBs Ag) positive (+) test or detected sensitivity on the HBV DNA PCR qualitative test for subjects who are hepatitis B core antibody (HBc Ab) positive (+) (and for hepatitis B surface antibody [HBs Ab] positive [+] participants where mandated by local requirements).
- •HCV: HCV RNA detectable in any participant with anti-HCV antibody (HCV Ab).
- •Human immunodeficiency virus (HIV), defined as confirmed positive anti-HIV Ab test and considered to have unstable disease (Unless meeting criteria for stable disease) Participants with HIV with no history of AIDS-defining conditions AND stable disease for at least 6 months prior to screening can be enrolled. Criteria for stable disease is achieved if all below criteria are met. Documentation of "stable disease" can be done at the Screening visit or by documentation of labs performed within 1 month of the Randomization visit, in addition to the subject's medical history.
- •On stable antiretroviral therapy;
- •Viral load (HIV RNA) below the lower limit of quantification by a validated and approved plasma HIV-1 RNA quantitative assay;
- •CD4+ T cell count ≥ 500 cells/μL.
- •- Participants with any of the following medical diseases or disorders:
- •Recent (within past 6 months) cerebrovascular accident or myocardial infarction;
- •History of an organ transplant which requires continued immunosuppression;
- •Active or suspected malignancy or history of any malignancy within the last 5 years except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.
- •Prior history of suicide attempt at any time in the subject's lifetime prior to signing the informed consent and randomization, or major depression or suicidal ideation or attempt requiring hospitalization within the last 3 years prior to signing the informed consent.
- •Hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
- •- Participants who received within 30 days prior to Baseline any:
- •Other systemic immunomodulating treatments (including, but not limited to:
- •e.g., methotrexate, apremilast, cyclosporine A, corticosteroids, cyclophosphamide, tofacitinib [Xeljanz®]);
- •Other systemic PsO treatments (e.g., retinoids, fumarates, any other drug known to possibly benefit PsO);
- •Photochemotherapy (e.g., PUVA), phototherapy (e.g., UVB) or prolonged exposure or use of tanning booths or ultraviolet light sources.
- •Participants who received within 14 days prior to Baseline any topical treatment for PsO or any other skin condition (including, but not limited to: e.g., corticosteroids, vitamin D analogues, vitamin A analogues, pimecrolimus, retinoids, salicyl vaseline, salicylic acid, lactic acid, tacrolimus, tar, urea, or anthralin).
- •Participants who have been treated with any strong cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin, St. John's Wort) within 30 days or 5 half-lives of start of treatment with deucravacitinib.
- •Participants who received any live viral or bacterial vaccine within 4 weeks prior to the first dose of study drug, or expect the need for live vaccination during study participation including at least 147 days (21 weeks or as guided by the local risankizumab label [if approved], whichever is longer) after the last dose of risankizumab or at least 30 days after the last dose of deucravacitinib.
- •Participants who have been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or be currently enrolled in another interventional clinical study.
研究组 & 干预措施
Period A: Arm 1 Risankizumab Dose A
Participants will be centrally randomized at the Baseline (Day 1) visit to receive Risankizumab as a single SC injection
干预措施: Risankizumab (Drug)
Period B: Arm 2a Risankizumab Dose A (Continued)
Participants initially randomized to risankizumab (Arm 1) will continue to receive risankizumab as a single SC injection at Weeks 16, 28, and 40
干预措施: Risankizumab (Drug)
Period A: Arm 2 Deucravacitinib Dose A
Participants will be centrally randomized at the Baseline (Day 1) visit to receive Deucravacitinib orally once per day until the day prior to Week 16
干预措施: Deucravacitinib (Drug)
Period B: Arm 2b Deucravacitinib Dose A
Participants initially randomized to Deucravacitinib (Arm 2) will be re-randomized at the Week 16 visit to receive Deucravacitinib orally once per day up to Week 52
干预措施: Deucravacitinib (Drug)
Period B: Arm 2a Risankizumab Dose A
Participants initially randomized to Deucravacitinib (Arm 2) will be re-randomized at the Week 16 visit to receive Risankizumab as a single SC injection at Weeks 16, 20, 32, and 44
干预措施: Risankizumab (Drug)
结局指标
主要结局
Period A: Percentage of Participants Achieving 90% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 90)
时间窗: At Week 16
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Period A: Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) Score of 0 (Clear) or 1 (Almost Clear) with at least 2-grade improvement from Baseline
时间窗: Baseline, Week 16
The static Physicians Global Assessment (sPGA) is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA composite score ranges from 0 to 4 and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean \>0, \<1.5; Mild (2) = mean ≥1.5, \<2.5; Moderate (3) = mean ≥2.5, \<3.5; and Severe (4) = mean ≥3.5.
Period B: Percentage of Participants Achieving 90% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 90) in the Intent to Treat Population for non-responders in Period B (ITT_B_NR).
时间窗: At Week 52
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Period A: Percentage of Participants Achieving 90% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 90)
时间窗: At Week 16
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Period A: Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) Score of 0 (Clear) or 1 (Almost Clear) with at least 2-grade improvement from Baseline
时间窗: Baseline, Week 16
The static Physicians Global Assessment (sPGA) is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA composite score ranges from 0 to 4 and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean \>0, \<1.5; Mild (2) = mean ≥1.5, \<2.5; Moderate (3) = mean ≥2.5, \<3.5; and Severe (4) = mean ≥3.5.
Period B: Percentage of Participants Achieving 90% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 90) in the Intent to Treat Population for non-responders in Period B (ITT_B_NR).
时间窗: At Week 52
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI 90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline \* 100.
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Baseline up to 73 Weeks
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered causally related to the use of the product.
次要结局
- Period A: Percentage of Participants Achieving 100% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 100)(At Week 16)
- Period B: Percentage of Participants Achieving 100% Improvement in Psoriasis Area Severity Index (PASI) Score (PASI 100) among participants in the ITT_B_NR Population(At Week 52)
- Period A: Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) Score of 0 with at least 2-grade improvement from Baseline(Baseline. Week 16)
- Period B: Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) Score of 0 with at least 2-grade improvement from Baselineamong participants in the ITT_B_NR Population.(At Week 52)