2024-512497-10-00招募中3 期
A Phase 3, Randomized, Multicenter, Double-Blind Trial to Evaluate the Efficacy, Safety, and Tolerability of Zasocitinib (TAK-279) Compared to Deucravacitinib in Participants With Moderate-to-Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 371
- 试验地点
- 48
- 主要终点
- 100% improvement from baseline in Psoriasis Area and Severity Index (PASI-100) response: Proportion of participants achieving PASI-100 at Week 16.
研究概览
简要总结
To evaluate whether zasocitinib orally administered once daily (QD) for 16 weeks is superior in efficacy to deucravacitinib 6 mg QD in participants with moderate-to-severe plaque psoriasis.
研究设计
- 分配方式
- Randomized
- 主要目的
- Safety Follow-up
- 盲法
- Double (Subject, Analyst, Investigator, Monitor)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Participant is willing and able to understand and fully comply with trial procedures and requirements (including digital tools and applications), in the opinion of the investigator.
- •For participants in the EU/EEA, the investigator must have no reason to believe that the participant would be placed at risk by participating in the trial with regard to the European Commission decision as of 10 March 2023 on measures to minimize risk of serious side effects with JAK inhibitors (EMA/142279/2023).
- •In the EU/EEA, for participants currently smoking or using chewing tobacco or with a history of long-term smoking (≥20 pack-years) or chewing tobacco use, the investigator must document a favorable benefit-risk assessment to justify the participant’s inclusion in the trial.
- •Participant has provided written informed consent and any required privacy authorization before the initiation of any trial procedures.
- •Participant has a diagnosis of chronic plaque psoriasis for ≥6 months prior to the screening visit.
- •Participant has stable plaque psoriasis, defined as no significant flare or change in morphology (as assessed by the investigator) in psoriasis, for ≥6 months before screening.
- •Participant has moderate-to-severe plaque psoriasis, as defined by a PASI score ≥12 and an sPGA score ≥3, at screening and Day
- •Participant has plaque psoriasis covering ≥10% of his or her total BSA at screening and Day
- •Participant must be a candidate for phototherapy or systemic therapy.
- •Participant is aged 18 years or older at the time of consent. In the EU/ European Economic Area (EEA), for participants aged 65 years or older, the investigator must document a favorable benefit-risk assessment to justify the participant’s inclusion in the trial.
- •Participant meets the following birth control requirement: An individual with potential for pregnancy who is now surgically sterile; or a participant of nonchildbearing potential with laboratory confirmation of postmenopausal status; or, if sexually active with a nonsterilized individual who produces sperm, an individual with potential for pregnancy who agrees to use a highly effective method of contraception from the signing of informed consent throughout the duration of the trial and for 10 days after the last dose. The use of effective contraception is not required for participants assigned male sex at birth during the duration of the trial. In the EU/EEA, for participants who elect to use hormonal contraception as a form of highly effective contraception, the investigator must document a favorable benefit-risk assessment at screening to justify the participant’s inclusion in the trial. Note: Oral hormonal contraception may be susceptible to interaction with zasocitinib, which may reduce the efficacy of the contraceptive method. Therefore, if the participant is on a form of oral contraception, a second highly effective or effective method of contraception should be used during the treatment period and for at least 10 days after the last dose of trial intervention, if the participant is sexually active with a partner with whom the participant could become pregnant. A barrier method is recommended, preferably a male condom.
排除标准
- •Participant has evidence of nonplaque psoriasis (erythrodermic, pustular, predominantly guttate psoriasis, predominantly inverse, or drug-induced psoriasis). If a participant meets criteria for inclusion based on typical plaque psoriasis presentation, a limited amount of inverse psoriasis is not exclusionary.
- •Participant has received any of the following biologics or biosimilar versions within the time frame indicated: a) Antibodies to IL-12/-23, IL-17, or IL-23 (for example, ustekinumab, secukinumab, tildrakizumab, ixekizumab, or guselkumab) within 6 months prior to Day
- •b) Tumor necrosis factor inhibitor(s) (for example, etanercept, adalimumab, infliximab, or certolizumab) within 2 months prior to Day
- •c) Agents that modulate integrin pathways to impact lymphocyte trafficking (for example, natalizumab) or agents that modulate B cells or T cells (for example, alemtuzumab, abatacept, or visilizumab) within 3 months prior to Day
- •d) Rituximab or other immune cell–depleting therapy within 6 months prior to Day
- •Participant has used medicated shampoo and/or body wash, including formulations containing but not limited to salicylic acid, corticosteroids, coal tar, vitamin D3 analogues, or other compounds used for the management of psoriasis within 2 weeks prior to Day
- •Participant has used any topical medication that could affect psoriasis presentation (including but not limited to corticosteroids, salicylic acid, urea, alpha- or beta-hydroxy acids, anthralin, retinoids, vitamin D analogues [such as calcipotriol], methoxsalen, trimethylpsoralen, calcineurin inhibitors [for example, tacrolimus], tapinarof, roflumilast, JAK inhibitors, or tar) within 2 weeks prior to Day
- •Note: Low-potency topical steroids (World Health Organization Class VI and VII or equivalent) are permitted on the palms, soles, face, and/or intertriginous areas, but should not be used within 24 hours before any trial visit. Low-potency topical steroids may be used to treat acute nonpsoriatic conditions (for example, contact dermatitis) on all body regions for no more than 2 weeks but should not be used within 24 hours before any trial visit. Low-potency topical steroids coformulated with other topicals that may affect the presentation of psoriasis are not permitted. Bland emollients (defined as emollients containing only ingredients that are pharmacologically inactive) are allowed on all body regions but should not be used within 24 hours before any trial visit."
- •"Participant has used any systemic nonbiologic treatment that could affect psoriasis presentation (including oral, intravenous, intramuscular, intra-articular, intrathecal, or intralesional corticosteroids; oral retinoids; immunosuppressive/immunomodulating medication; methotrexate; azathioprine; 6-thioguanidine; mercaptopurine; mycophenolate mofetil; hydroxyurea; cyclosporine; 1,25-dihydroxyvitamin D3 analogues; psoralens; sulfasalazine; fumaric acid derivatives; JAK inhibitors; apremilast) within 4 weeks prior to Day 1 or 5 half-lives, whichever is longer. Note: Intranasal corticosteroids, inhaled corticosteroids, and eye and ear drops containing corticosteroids are permitted."
- •Participant has used leflunomide within 6 months prior to Day
- •Participant has received phototherapy (including ultraviolet [UV] B, psoralen and UV A, tanning beds, therapeutic sunbathing) or excimer laser within 4 weeks prior to Day
- •Participant has used botanical preparations (for example, herbal supplements or traditional Chinese medicines derived from plants, minerals, or animals) intended to treat psoriasis or other immunological diseases within 4 weeks prior to Day
- •Participant is currently being treated with oral antihistamines for any reason, with the exception of oral antihistamines that are administered at a stable dose for at least 4 weeks prior to Day
- •Note: Additional treatment with oral antihistamines may be permitted after discussion with the medical monitor.
- •Participant has any previous exposure to zasocitinib (also known as TAK-279 or NDI-034858) or other TYK2 inhibitors (including deucravacitinib),or participated in any trial that included a TYK2 inhibitor (for example, deucravacitinib, VTX958, GLPG3667, et cetera), unless participant has documentation of posttrial unblinding that confirms the participant did not receive a TYK2 inhibitor.
- •Participant has received lithium, antimalarials, or intramuscular gold therapy within 4 weeks prior to Day
- •Participant requires systemic treatment, other than nonsteroidal anti-inflammatory drugs, during the trial period for an immune-related disease (for example, inflammatory bowel disease).
- •Participant is currently being treated with strong or moderate CYP3A4 inhibitors (such as itraconazole) or strong or moderate CYP3A4 inducers (such as rifampin, carbamazepine, or phenytoin), or has received strong or moderate CYP3A4 inhibitors or strong or moderate CYP3A4 inducers within 4 weeks or 5 half-lives of the inducer or inhibitor, whichever is longer, prior to Day 1, or is anticipated to require treatment with strong or moderate CYP3A4 inducers or inhibitors during the trial period (Appendix 1). Note: This includes consumption of food or beverages containing grapefruit and/or Seville oranges within 1 week of Day
- •Participants must be counseled to avoid food or beverages containing grapefruit and/or Seville oranges for the duration of the trial."
- •Participant has received any live-attenuated vaccine within 60 days prior to Day 1 or plans to receive a live-attenuated vaccine during the trial and up to 4 weeks after the last trial intervention administration. Note: Non–live-attenuated vaccines or boosters for COVID-19 or influenza are permitted during the trial."
- •Participant received an investigational antibody or biologic therapy within 6 months prior to Day
- •Participant received an investigational oral therapy within 3 months prior to Day
- •Participant is currently receiving a nonbiological trial intervention or device or has received one within 4 weeks prior to Day
- •Participant is currently enrolled in a clinical trial or anticipates enrollment in a clinical trial during the course of the trial.
- •Participant has any of the following laboratory values at the screening visit: a) AST or ALT values ˃3 × ULN. b) Tbili (unconjugated and/or conjugated) ˃1.5× ULN. c) Hemoglobin <9.0 g/dL (<90.0 g/L). d) Absolute WBC count <3.0×109/L (<3000/mm3). e) Absolute neutrophil count of <1.0×109/L (<1000/mm3). f) Absolute lymphocyte count of <0.5×109/L (<500/mm3). g) Platelet count <100×109/L. h) Thyroid-stimulating hormone outside the normal reference range AND free T4 or T3 outside the normal reference range. i) Estimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation. j) CPK > ULN. CPK may be repeated once; if repeat value is CTCAE Grade 1 or lower (or ≤2.5 × ULN) and no higher than the initial value, participant remains eligible. Investigators should assess the participant for modulating factors, including concomitant medications or vigorous exercise, that may affect CPK levels. "
- •Participant has any other significant laboratory abnormalities that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this trial.
- •Participant does not tolerate venipuncture or inability to be venipunctured.
- •Participant has history of significant drug allergy (such as anaphylaxis).
- •Participant has a history of excessive sun exposure, has used tanning booths within 4 weeks prior to Day 1, or is not willing to minimize natural and artificial sunlight exposure during the trial period. Use of sunscreen products and protective apparel is recommended when sun exposure cannot be avoided.
- •Participant has a known or suspected allergy to zasocitinib or deucravacitinib or any of their components.
- •Participant has a positive pregnancy test result or plans to become pregnant during the trial period, or participant is pregnant or lactating/nursing.
- •Participants who have given greater than 500 mL of blood or plasma within 30 days of screening (during a clinical trial or at a blood bank donation) or plans to donate blood during the course of the trial.
- •Participant is compulsorily detained for treatment of either a psychiatric or physical (for example, infectious disease) illness, or is committed to an institution (for example, prison) by virtue of an order issued either by judicial or administrative authorities.
- •Participant is a trial site employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with trial site employee who is involved in the conduct of this trial, or may consent under duress.
- •Participant has concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the trial assessments.
- •Tuberculosis (TB): a) Participant has history of active TB infection, regardless of treatment status. b) Participant has signs or symptoms of active TB (including, but not limited to, chronic fever, chronic productive cough, night sweats, or weight loss) as judged by the investigator. c) Participant has evidence of latent TB infection (LTBI) as evidenced by a positive QuantiFERON-TB Gold (QFT) result OR 2 indeterminate QFT results and participant does not have documentation of appropriate LTBI prophylaxis or is not able or not willing to initiate appropriate LTBI prophylaxis. Participant remains eligible if there are no signs/symptoms of active TB AND documentation of no history of active TB can be provided AND: (1) participant can provide documentation of prior and complete treatment for LTBI (appropriate in duration and type per current local country guidelines) or (2) participant has a positive QFT result or 2 indeterminate QFT results but has initiated prophylaxis (appropriate in duration and type per current local guidelines) a minimum of 2 weeks prior to Day
- •In the EU/EEA, participants with evidence of LTBI, regardless of prophylaxis treatment status, must receive approval to participate in the trial from an infectious disease or other TB specialist (for example, pulmonologist). Note: TB prophylaxis regimens should be administered according to local guidelines; however, because of potential interactions with zasocitinib, rifampin should not be used. TB testing should be conducted using QFT submitted to the central laboratory unless alternate or additional tests are required per local guidelines. d) Participant has had any imaging trial during or 6 months prior to screening, including x-ray, chest computed tomography, magnetic resonance imaging, or other chest imaging suggesting evidence of current active or a history of active TB. X-ray is required for all participants regardless of QFT results unless the participant has had normal chest imaging in the 6 months prior to screening."
- •Herpes infections: a) Participant has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 (demonstrated on physical examination and/or medical history) at screening or Day
- •b) Participant has history of serious herpetic infection that includes any episode of disseminated disease, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (defined as 2 episodes within 2 years)."
- •Nonherpetic viral diseases: a) Participant has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction). In the EU/EEA, if the participant has total anti-HCV antibody (Ab) positivity at screening but is confirmed to have no detectable HCV RNA by polymerase chain reaction (PCR) testing, HCV RNA PCR testing will be assessed per the SoA. b) Participant has presence of positive hepatitis B surface antigen (HBsAg+), or indeterminant HBsAg, presence of hepatitis B virus DNA (regardless of serology), or positive anti-hepatitis B core antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-). In the EU/EEA, if the participant has total anti-HBcAb positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, the participant will repeat HBV DNA PCR testing per the SoA; if a participant has anti-HBsAb positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, unless the participant has documented completion of the HBV vaccination series by medical records, the participant will repeat HBV DNA PCR testing per the SoA. c) Participant has positive results for human immunodeficiency virus (HIV) by serology, regardless of viral load.
- •Other infectious diseases: a) Participant has a history of active infection or febrile illness within 7 days prior to Day 1, as assessed by the investigator. b) Participant has history of symptoms suggestive of systemic or invasive infection within 30 days prior to Day
- •c) Participant has history of bacterial, viral, or fungal infection that required hospitalization or treatment with intravenous antimicrobial therapy within 8 weeks prior to Day 1 or oral antimicrobial therapy within 30 days prior to Day
- •d) Participant has a history of chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or chronic skin ulcerations/infections or fungal infections (except superficial onychomycosis). e) Participant has a history of an infected joint prosthesis, unless that prosthesis has been removed or replaced within 60 days prior to Day
- •f) Participant has a history of opportunistic infections (for example, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis). g) Participant had a bacterial infection within 60 days prior to Day 1 for which he or she did not receive treatment."
- •Participant has any clinically significant medical condition, evidence of an unstable clinical condition (for example, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of trial results. These include but are not limited to: a) Participant has a history of known or suspected condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency; splenectomy. b) Participant had a major surgery within 60 days prior to Day 1 or has a major surgery planned during the trial. c) Participant has unstable, poorly controlled, or severe hypertension at screening, confirmed by 2 repeat assessments. d) Participant has a history of Class III or IV congestive heart failure as defined by New York Heart Association criteria. e) Participant has a history of cancer or lymphoproliferative disease, with the exception of successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix; in the EU/EEA, investigators must specifically document a favorable benefit-risk assessment. f) For participants with asthma, chronic obstructive pulmonary disease, or other pulmonary illnesses, participant has been hospitalized in the past 3 months, has ever required intubation for treatment, currently requires oral corticosteroids, or has required more than 1 course of oral corticosteroids within 6 months prior to Day
- •g) Participant has any of the following cardiovascular disease history: • A new diagnosis of atrial fibrillation or an episode of atrial fibrillation with rapid ventricular response or other dysrhythmia, nonacute cardiac hospitalization (for example, pacemaker implantation), pulmonary embolism, or deep venous thrombosis within the past 6 months prior to screening. • Any history of cerebrovascular event, myocardial infarction, coronary stenting, or aorto-coronary bypass surgery. If, however, the investigator determines there are no suitable treatment alternatives available for the participant and it has been at least 6 months since the occurrence of any such event, the participant may enroll; in the EU/EEA, investigators must specifically document a favorable benefit-risk assessment. h) Participant has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the participant if he or she participated in the trial, in the opinion of the investigator. i) Participant has significant/uncontrolled psychiatric illness, in the opinion of the investigator. j) Participant has a history of clinically significant drug or alcohol abuse within 12 months prior to Day 1.
结局指标
主要结局
100% improvement from baseline in Psoriasis Area and Severity Index (PASI-100) response: Proportion of participants achieving PASI-100 at Week 16.
100% improvement from baseline in Psoriasis Area and Severity Index (PASI-100) response: Proportion of participants achieving PASI-100 at Week 16.
次要结局
- 1. PASI-90 response: Proportion of participants achieving PASI-90 at Week 16.
- 2. Absolute PASI ≤2 response: Proportion of participants achieving PASI ≤2 at Week 16.
- 3. Enhanced static Physician’s Global Assessment (sPGA) response: Proportion of participants achieving an sPGA of clear (0) at Week 16.
- 4. PASI-100, PASI-90, sPGA 0, and absolute PASI ≤2 response at Weeks 4, 8, and 12.
- 5. PASI-75 and sPGA 0/1 at Weeks 4, 8, 12, and 16.
- 6. Change from baseline and percent change from baseline in PASI score at Weeks 4, 8, 12, and 16.
- 7. Incidence of treatment-emergent adverse events (TEAEs)
- 8. Incidence of serious adverse events (SAEs).
- 9. Incidence of adverse events of special interest (AESIs).
- 10. Changes in vital signs, clinical laboratory parameters, and electrocardiogram (ECG).
研究者
Takeda
Scientific
Takeda Development Center Americas Inc.
研究点 (48)
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