Arthritic Psoriasis
Conditions
Keywords
arthritic psoriasis adults
Brief summary
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
Detailed description
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
Interventions
DRUGCBP-0276 capsules 100mg
capsule with CBP-0276 powder
DRUGPlacebo
Capsule with placebo for CBP-0276
Sponsors
Clarent Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (participant, care provider, investigator, outcomes assessor). The participant, study operating staff and sponsor will remain blind to the assigned treatment. To ensure such masking, a non-blind pharmacist delegated by the Principal Investigator will be responsible for dispensing the investigational product. The Sponsor and the research center will have two blind/non-blind teams. The study interventions (CLT-0276 and placebo) will have the same pharmaceutical form (capsule) and will be dispensed in containers/dosers previously identified with the ID number that corresponds to each subject. The containers will be made of plastic and identical for both products and labelled with the following information: protocol number and ID number. The analysts' blindness will remain with respect to the randomization scheme
Intervention model description
Randomized, double-blind, multicenter, placebo-controlled phase 2 clinical study, comprised for a 2-week total screening period, a 24-week blinded core treatment period, and 4-week follow-up observational period. Subject will be allocated to receive 200mg QD (branch A), 800mg QD (branch B) or placebo for 24 weeks
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change on severity of symptoms at lest 20% at week 24 | week 24 after randomization | Proportion of randomized subjects achieving American College Rheumatologic Score (ACR) at least 20% (ACR20) response at Week 24. ACR is a validated score that measure improvement after begining of therapy in arthritis. Minimum valure 20% represents te minimum improvement and ACR 75% to 100% represents the highest improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of severity of symptoms at week 16 | week 16 after randomization | Proportion of randomized subjects achieving American College Rheumatologic Score at least 20% (ACR20) response at Week 16. Minimum value is 0% and maximum is 100% |
| Magnitude of change on ACR 50/70% | week 4, 8, 12, 16, 20 and 24 after randomization | Proportion of subjects achieving American College Rheumatologic Score (ACR) at least 50/70% from baseline to week 4, 8, 12, 16, 20 and 24. Minimum value is 0% and maximum is 100% |
| Changes on disease activity | week 4, 8, 12, 16, 20 and 24 after randomization | Change from baseline in the DAS 28-joint count using Hs-CRP (DAS28-HsCRP) at week 4, 8, 12, 16, 20 and 24. The DAS28-CRP (Disease Activity Score in 28 joints using C-Reactive Protein) is a composite index used by rheumatologists to measure the disease activity of Rheumatoid Arthritis (RA). It evaluates inflammation through swollen/tender joint counts, a patient's overall health assessment, and a standard or high-sensitivity CRP (hs-CRP) blood test. Minimum value is 0.96 no activity and maximum is 9.4 which means maximal activity |
| Changes on disability index | week 4, 8, 12, 16, 20 and 24 after randomization | Change from baseline in the HAQ-DI at week 4, 8, 12, 16, 20 and 24. The Health Assessment Questionnaire Disability Index (HAQ-DI) is a widely used patient-reported tool that measures a patient's physical functional ability and daily living limitations (often used for conditions like arthritis). It evaluates 20 daily activities across eight categories (dressing, arising, eating, walking, hygiene, reach, grip, and common activities). Minimum is 0 which means no disability and maximum is 3 which means maximum disability |
| Changes on dactilitis severity | week 4, 8, 12, 16, 20 and 24 after randomization | Change from baseline in Leeds Dactilitis Index-Basics at week 4, 8, 12, 16, 20 and 24. The Leeds Dactylitis Index-Basic (LDI-B) is a validated, objective clinical tool used to measure the severity and activity of dactylitis (inflammation/swelling of entire fingers or toes) in conditions like psoriatic arthritis. Minim value is cero (no activity) and maximum could reach around 3,000 which means maximum dactilitis activity |
| Changes on quality of life | week 4, 8, 12, 16, 20 and 24 after randomization | Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 4, 8, 12, 16, 20 and 24. The HAQ-DI (Health Assessment Questionnaire - Disability Index) is a widely used, standardized patient-reported questionnaire designed to measure a person's functional status and ability to perform daily living activities. It is frequently used to monitor conditions like rheumatoid arthritis, osteoarthritis, and other rheumatic disease. Minimum value is 0 and maximum value is 3 |
| Changes on psoriasis activity | week 4, 8, 12, 16, 20 and 24 after randomization | Change from baseline in the Psoriasis Area and Severity Index (PASI 75 and PASI 90; in patients with body surface area affected by psoriasis ≥3% at baseline) 4, 8, 12, 16, 20 and 24. The PASI (Psoriasis Area and Severity Index) is the standard clinical tool used by dermatologists to measure the overall severity and body coverage of psoriasis. It is commonly calculated in clinical trials and doctor's offices to track disease progression and treatment effectiveness. Minimum valaue is 0 (no activity) and maximum is 72 (Maximum activity) |
| Changes on tender joint count | week 4, 8, 12, 16, 20 and 24 after randomization | Changes on TJC68 Score from baseline to week 4, 8, 12, 16, 20 and 24 after randomization. The TJC68 score (Tender Joint Count 68) is a standardized clinical measurement used in rheumatology to evaluate joint pain across 68 specific joints in the body. It is primarily used to assess the severity and peripheral arthritis activity of diseases like Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). Minimum value is 0 and maximum is 68 |
| Changes on patient's level of fatigue and its impact on daily life | week 4, 8, 12, 16, 20 and 24 after randomization | Changes on FACIT-Fatigue Score from baseline to week 4, 8, 12, 16, 20 and 24 after randomization. The FACIT-Fatigue Scale is a 13-item questionnaire used to measure the severity of fatigue and its impact on daily activities. It asks patients to rate their fatigue-related experiences over the past 7 days on a 5-point Likert scale, ranging from 0 (Not at all) to 4 (Very much). Minimum is 0 and maximum is 52 |
| Frequency and severity of adverse events | week 4, 8, 12, 16, 20 and 24 after randomization | The frequency of AESIs evaluated by Full version of MEDRA Ver. 28.0 |
Countries
Mexico
Contacts
CONTACTPedro Gutierrez Castrellon, MD, PhD
CONTACTDiana M Andrade Platas, MD
PRINCIPAL_INVESTIGATORDiana Gómez Marin, MD
Innovación y Desarrollo en Ciencias de la Salud SRL de CV
Outcome results
None listed