Oral CBP-0276 or Placebo in Adults With Active Psoriatic Arthritis (PsA)

Официальное название

A Phase 2 Randomized, Double Blind, Clinical Trial (RCT) to Assess the Efficacy, Safety, and Tolerability of Oral CBP-0276 200mg QD, 800mg QD or Placebo for CBP-0276, Administered to Adults With Active Psoriatic Arthritis (PsA).

Обзор

Randomized trial aimed to assess in adults with PsA the effect of oral CBP-0276 administrated at a dose of 200mg QD, or 800mg QD vs. Placebo for CBP-0276 for 24 weeks. Primary outcome is the change at least 20% on severity of symptoms eat week 24, using the American College Rheumatologic Score (ACR) and key secondary outcomes are the change on ACR20% at week 16 and ACR50/70% at week 24. Eligible patients will be randomly assigned (1:1:1) to receive oral CBP-0276 200mg QD, 800mg QD or placebo for CBP-0276 for 24 weeks

Подробное описание

Randomized trial aimed to assess in adults with PsA the effect of oral CBP-0276 administrated at a dose of 200mg QD, or 800mg QD vs. Placebo for CBP-0276 for 24 weeks. Primary outcome is the change at least 20% on severity of symptoms eat week 24, using the American College Rheumatologic Score (ACR) and key secondary outcomes are the change on ACR20% at week 16 and ACR50/70% at at week 24. Additional secondary outcome include a) ACR50/70% at week 4, 8, 12, 16 and 20; b) changes on Disease Activity at week 4, 8, 12, 16, 20 and 24; c) Changes on disability index at week 4, 8, 12, 16, 20 and 24; d) Changes on dactilitis and enthesitis severity; d) Changes on Quality of Life and e) Changes on plaque psoriatic activity. Exploratory outcomes include changes at week 4,8,12,16 and 24 on a) tender joint count; b) global patient evaluation and c) patient level of fatigue and imapct on daily life. Elegible patients are 18-75 years, BMI between 18 and 39 kg/m2, fulfill the classification criteria for PsA, had symptoms for at least 6 months and less than 12 months before screening, had active disease at baseline (3 of 68 or more tender joints and 3 of 66 or more swollen joints), had at least one active plaque psoriatic lesion or documented history of plaque psoriasis and failed to respond or stabilize on NSAIDs and/or csDMARDs will be included. Enrolled patients will be randomly assigned (1:1:1) to receive oral CBP-0276 200mg QD, 800mg QD or placebo for CBP-0276 for 24 weeks

Вмешательства

• Препарат CBP-0276 capsules 100mg
  capsule with CBP-0276 powder
• Препарат Placebo
  Capsule with placebo for CBP-0276

Первичные конечные точки

• Change on severity of symptoms at lest 20% at week 24 [Срок оценки: week 24 after randomization]

Вторичные конечные точки (10)

• Change of severity of symptoms at week 16 [Срок оценки: week 16 after randomization]
• Magnitude of change on ACR 50/70% [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on disease activity [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on disability index [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on dactilitis severity [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on quality of life [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on psoriasis activity [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on tender joint count [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Changes on patient's level of fatigue and its impact on daily life [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]
• Frequency and severity of adverse events [Срок оценки: week 4, 8, 12, 16, 20 and 24 after randomization]

Критерии участия

Критерии включения

• Subject must voluntarily sign the informed consent form before any study-related procedures, understand and communicate with the investigator smoothly during the trial, and understand and voluntarily strictly abide by the provisions of this clinical study protocol;
• Age ≥ 18 years and ≤ 75 years at the time of signing the informed consent form, male or female;
• Body Mass Index (BMI) ≥ 18 and ≤ 39 kg/m2 at screening;
• Fulfilled the 2006 Classification Criteria for Psoriatic Arthritis (CASPAR) and had symptoms of psoriatic arthritis for more than 6 months but less than 12 months of evolution at screening
• Had active PsA before randomization (defined as ≥ 3/68 tender joint count and ≥ 3/66 swollen joint count);
• Active plaque psoriasis (at least one plaque lesion) at screening, or a history of plaque psoriasis;
• Failure to respond or stabilize on NSAIDs and/or csDMARDs (Inadequate Responders)
• Female subjects of childbearing potential must have a negative pregnancy test during the screening period and prior to randomization.

Критерии исключения

• History of Drug-induced psoriasis (including, but not limited to, psoriasis induced by beta-blockers, calcium channel inhibitors, or lithium);
• Had other active inflammatory diseases or autoimmune diseases other than psoriatic arthritis, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, reactive arthritis, inflammatory bowel disease arthritis, etc.;
• History of organ transplantation (except for corneal transplantation within 3 months prior to screening;
• History of lymphoproliferative disorders, including symptoms and signs of lymphoma or underlying lymphoproliferative disorders;
• Had a serious infection (systemic infection, use of intravenous anti-infective therapy, or hospitalization due to infection) within 4 weeks prior to screening, or had an active or chronic infection at screening that the investigator considers unsuitable for inclusion in this trial;
• History of severe opportunistic infections (including but not limited to Pneumocystis carinii pneumonia, coccidioidomycosis, etc.) or immunodeficiency disease;
• History of invasive fungal infection;
• Any active malignancy or history of malignancy within 5 years prior to screening, with the exception of cured squamous or basal cell carcinoma of the skin or in situ cervical cancer;
• Joint surgery (including but not limited to meniscectomy, joint transplant, joint replacement, arthrodesis, etc.) within 8 weeks prior to screening; or the joint had not recovered after surgery (including but not limited to incision infection, unhealed wound, open drainage, etc.) at the time of screening;
• Major surgery within 8 weeks prior to screening, or planned surgery during the study;
• Had donated or lost ≥ 400 mL of blood within 8 weeks prior to randomization and/or planned to donate blood during the study;
• History of moderate to severe congestive heart failure (New York Heart Association \[NYHA\] functional class ≥ III), cardiovascular events, or severe bleeding events within 3 months prior to screening;
• Subjects with serious, progressive, uncontrolled cardiovascular and cerebrovascular diseases, liver, kidney, lung, gastrointestinal tract, hematopoietic system, endocrine system, nervous system diseases, or other conditions that the investigator considered unsuitable for this trial;
• Subjects with a history of depression and/or active suicidal ideation as assessed by Sheehan-Suicidality Tracking Scale (S-STS) or any suicide attempt, suicidal behavior, or clinical judgment of the investigator to be at risk of suicide during the screening period were excluded;
• Subjects with a history, symptoms and examination findings suggestive of active TB or latent TB at screening.
• Positive test for hepatitis B, C, syphilis, or human immunodeficiency virus (HIV) antibody at screening;
• Use of any of the following medications or participation in a clinical study (defined as signed informed consent): A) Use of any biologic drugs in the last 6 months, such as a TNF inhibitor within a specified time period prior to randomization (e.g., use of recombinant human tumor necrosis factor receptor-antibody fusion protein within 4 weeks prior to randomization; subjects who had received infliximab within 8 weeks before randomization; received adalimumab, golimumab, or certolizumab within 10 weeks before randomization); B) Had used at least 2 bDMARDs (including at least 2 different classes of TNF inhibitors) before randomization; C) Subjects who had used traditional synthetic disease-modifying antirheumatic drugs (csDMARDs) or systemic immunosuppressive agents (such as cyclophosphamide, cyclosporine, azathioprine, and mycophenolate mofetil) other than MTX, LEF, PDE-4 inhibitor, or SSZ within 4 weeks before randomization; D) Subjects who had received psoriatic arthritis or psoriasis herbal preparations patent medicines (such as Tripterygium wilfordii, total glucosides of peony, sinomenine, and kunxian) within 4 weeks before randomization; E) Had received any intra-articular injection therapy (such as glucocorticoids and hyaluronic acid) within 4 weeks before randomization; F) Phototherapy/photochemotherapy (including psoralen and ultraviolet A (PUVA) phototherapy, ultraviolet B (UVB) within 4 weeks prior to randomization; G) Received topical psoriasis treatments/other systemic treatments within 4 weeks prior to randomization, such as topical corticosteroids, vitamin D3 derivatives, or retinoids; however, the following topical treatments were allowed: non-medical scalp lotions (i.e., without glucocorticoids or vitamin D3 derivatives, calcineurin inhibitors, etc.), mild emollients (without alpha or beta hydroxy acids, urea, salicylic acid); H) Oral, intravenous, or intramuscular glucocorticoids within 4 weeks prior to randomization; I) Prior exposure to anti-interleukin 17 (IL-17), anti-IL-17 receptor, anti-IL-12/IL-23, and IL-23p19 agents; J) Used of other biologic agents for the treatment of psoriasis/psoriatic arthritis within 6 months or 5 half-lives (whichever is longer) prior to randomization (including but not limited to, for example, anti-IL-6, anti-CD20 monoclonal antibody, CTLA4 antibody) or JAK inhibitor; K) Subjects who had used other clinical trial drugs, vaccines or medical devices or were expected to have residual effects of the trial treatment within 2 weeks or 5 half-lives (whichever is longer) before randomization (except for those who are clearly given placebo throughout the trial); L) Subjects who are allergic to the ingredients or excipients of the investigational product, or to other biological agents; M) Had received a live attenuated vaccine within 12 weeks prior to randomization, or planned to receive a live attenuated vaccine during the study, or within 20 weeks after the end of study treatment; or N) Had used strong opioid analgesics (such as methadone, morphine, hydromorphone, etc.) within 6 weeks prior to randomization.
• Abnormal and clinically significant screening laboratory value that, in the opinion of the investigator, would pose an unacceptable risk to the subject if he or she participated in the study, or any of the following abnormalities as specified: A) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) ≥ 3x upper limit of normal (ULN); or total bilirubin or gamma-glutamyl transpeptidase (GT) ≥ 1.5 times the ULN; B) Serum creatinine ≥ 1.5 times ULN; C) Hemoglobin < 85.0 g/L for male subjects and < 80.0 g/L for female subjects; D) Total leukocyte count (WBC) < 3.0 \* 109/L; E) Neutropenia (neutrophils < 1.5 \* 109/L); or F) Thrombocytopenia (platelets < 100 \* 109/L);
• Pregnant or lactating (pregnancy is defined as the state after conception and until the termination of gestation);
• Subjects of childbearing potential who are pregnant or planning to donate sperm/ova or are unwilling to take highly effective contraceptive measures from the signing of the informed consent form to 20 weeks (5 half-lives) after the use of the investigational product;
• History of alcohol or illicit drug abuse within one year prior to screening;
• Any other condition that, in the opinion of the investigator, would prevent the subject from following and completing the study protocol or interfere with the study analysis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Мексика · 1 центр

• Innovacion y Desarrollo en Ciencias de la Salud (IDeCSa) — Mexico City

Публикации

• Alinaghi F, Calov M, Kristensen LE, Gladman DD, Coates LC, Jullien D, Gottlieb AB, Gisondi P, Wu JJ, Thyssen JP, Egeberg A. Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol. 2019 Jan;80(1):251-265.e19. doi: 10.1016/j.jaad.2018.06.027. Epub 2018 Jun 19. PMID 29928910
• Eder L, Haddad A, Rosen CF, Lee KA, Chandran V, Cook R, Gladman DD. The Incidence and Risk Factors for Psoriatic Arthritis in Patients With Psoriasis: A Prospective Cohort Study. Arthritis Rheumatol. 2016 Apr;68(4):915-23. doi: 10.1002/art.39494. PMID 26555117
• FitzGerald O, Ogdie A, Chandran V, Coates LC, Kavanaugh A, Tillett W, Leung YY, deWit M, Scher JU, Mease PJ. Psoriatic arthritis. Nat Rev Dis Primers. 2021 Aug 12;7(1):59. doi: 10.1038/s41572-021-00293-y. PMID 34385474
• Singh JA, Guyatt G, Ogdie A, Gladman DD, Deal C, Deodhar A, Dubreuil M, Dunham J, Husni ME, Kenny S, Kwan-Morley J, Lin J, Marchetta P, Mease PJ, Merola JF, Miner J, Ritchlin CT, Siaton B, Smith BJ, Van Voorhees AS, Jonsson AH, Shah AA, Sullivan N, Turgunbaev M, Coates LC, Gottlieb A, Magrey M, Nowell WB, Orbai AM, Reddy SM, Scher JU, Siegel E, Siegel M, Walsh JA, Turner AS, Reston J. Special Arti PMID 30499246
• Nash P. Inhibition of interleukins 17A and 17F in psoriatic arthritis. Lancet. 2020 Feb 8;395(10222):395-396. doi: 10.1016/S0140-6736(20)30220-8. No abstract available. PMID 32035535
• Lee BW, Moon SJ. Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment. Int J Mol Sci. 2023 Jul 19;24(14):11662. doi: 10.3390/ijms241411662. PMID 37511421
• McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewe R, Conaghan PG, Gottlieb AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S; FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 Sep 19;386(99 PMID 26135703

Идентификаторы

NCT: NCT07706530 · CBP-0276-PsA01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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