Takayasu Arteritis (TAK)
Conditions
Keywords
Deucravacitinib, Adalimumab, Relapsed, Efficacy, Safety, Takayasu arteritis
Brief summary
This is a 24-week, single-center, randomized, open-label trial conducted by Peking Union Medical College Hospital. The aim of this study is to assess the efficacy and safety of deucravacitinib in adult patients with relapsing TAK in comparison to patients treated with TNF inhibitor (TNFi), the most well-recognized therapeutic choice of non-glucocorticoid immunosuppressive for patients with relapsed or refractory TAK.
Detailed description
Background: The majority of patients with TAK experience relapses, and some patients fail to respond adequately to current medications used for treatment of TAK. There is an urgent unmet need to identify novel therapies to effectively treat TAK. Th-17 and Th-1 cells, and their related cytokines IL-12, IL-23, IL-17, and type I interferon have all been reported to play a role in the pathogenesis of TAK. Tyrosine kinase 2 (TYK2) mediates signaling transduction between these key cytokines and immune cells. Therefore, blocking TYK2 signaling may downregulate potential pathogenic pathways in TAK, and may be a therapeutic alternative. No study has investigated the effectiveness of agents targeting TYK2 in the treatment of TAK so far. In the present study, we aim to investigate whether deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, is effective and safe for patients with relapsed TAK. Objectives: To assess the efficacy and safety of deucravacitinib in adult patients with relapsing TAK in comparison to patients treated with TNF inhibitor (TNFi), the most well-recognized therapeutic choice of non-glucocorticoid immunosuppressive for patients with relapsed or refractory TAK. Overall Design: This is a 24-week, single-center, randomized, open-label trial conducted by Peking Union Medical College Hospital. Patients enrolled into the study are randomly assigned (in a 1:1 ratio, 25 patients in each group) to receive deucravacitinib or adalimumab (a TNFi). Patients are followed for efficacy and safety at month 1, month 3, and month 6. Adverse events/Serious adverse events are assessed and recorded at each visit.
Interventions
DRUGDeucravacitinib
Deucravacitinib is a new, oral, selective, allosteric inhibitor of TYK2. It was first approved in the United States on 09-Sep-2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
DRUGAdalimumab
TNFα inhibitors have already been used in TAK treatment. Several retrospective studies have demonstrated the treatment effects of these agents in patients with TAK, including disease remission, GC tapering and vascular inflammation control. According to the ACR and EULAR guidelines, TNFis are recommended to be considered in cases of relapsing or refractory TAK. These agents (including adalimumab) are the most frequently analyzed therapeutic modalities in recent studies of TAK.
Sponsors
Chinese SLE Treatment And Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
prospective, single-center, randomized, open-label trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants are eligible to be included in the study only if all of the following criteria apply: 1. Signed Written Informed Consent 1. Participants fully understand the purpose, nature, method, and possible adverse reactions of the study, willing to consent to the trial and follow study protocol and sign informed consent. 2. Participants must have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines. This ICF must be obtained before performing any protocol related procedures that are not part of normal patient care. 2. Type of Participant and Target Disease Characteristics 1. Adult patients (aged 18 or older) fulfilling the 2022 ACR/EULAR classification criteria for TAK. 2. Persistence of active disease or relapse despite treatment with GCs combined with a conventional synthetic or biologics immunosuppressive agent other than TNFi. 3. Active vasculitis by reader interpretation of FDG-PET at enrollment (by the same reader). 3. Reproductive Status The investigator or designee shall counsel women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. WOCBP must have a negative highly sensitive specify: urine or serum as required by local regulations pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention. A female is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \< 1% per year) during the intervention period and for at least 5 half-lives after product administration and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period. WOCBP and male participants who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception.
Exclusion criteria
* Participants are excluded from the study if any of the following criteria apply: 1. Medical Conditions 1. Severe disease from TAK for which urgent treatment with interventional procedures or bypass surgery is considered necessary 2. Critical organ involvement of TAK, such as myocardial or coronary artery involvement, or cerebral ischemia 3. Active hepatitis B or C virus infection, active tuberculosis infection 4. Malignancy in the past 5 years (with the exception of fully excised non-melanoma skin cancer or cervical carcinoma in situ) 2. Physical and Laboratory Test Findings 1. Serum liver enzyme tests 3 times higher than the upper limits of normal range 2. Estimated glomerular filtration rate ≤ 30 ml/minute 3. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate at week 24 | Week 24 | * Overall response is defined as the combination of both complete and partial responses. * Complete (treatment) response is defined as the absence or complete resolution of clinical signs and symptoms of active TAK and a patient achieving all of the following: 1. ESR \<20mm/hour; 2. CRP \<10mg/L; 3. No progression of vessel damage in Doppler ultrasonography or CTA, including no new or worsening mural thickness, or stenosis or dilatation; 4. Dose of GC \<15 mg/day prednisone (or equivalent dosage of other GCs). * Partial (treatment) response is defined as the absence or complete resolution of clinical signs and symptoms of active TAK and: 1. ESR \<40mm/hour or decrease by 50% compared to the baseline value; 2. CRP \<20mg/L or decrease by 50% compared to the baseline value; 3. fulfilling the other two criteria of complete response. * The absence or complete resolution of clinical signs and symptoms of active TAK is a pre-required criterion for both complete and partial |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease recurrence after achieving clinical remission | from inclusion to the end of the study, 24 weeks in total | recurrence rate after achieving clinical remission |
| Time to disease recurrence | from inclusion to the end of the study, 24 weeks in total | time from clinical remission to disease recurrence |
| Changes in erythrocyte sedimentation rate (ESR) | week 4, 12 and 24 | Erythrocyte sedimentation rate (ESR) is an indicator of systemic inflammation, will be reported in mm/h. |
| Time to clinical remission | from inclusion to the end of the study, 24 weeks in total | time from the baseline to achieve clinical remission |
| Changes in vascular ultrasonography | from baseline to weeks 12 and 24 | Vascular Doppler ultrasonography of the carotid arteries, subclavian arteries and abdominal aorta |
| Changes in PET/CT scans | from the baseline to week 24 | PET-CT, including 18F-FDG PET/CT and 68Ga-FAPI PET/CT are performed at baseline and at the end of the study to assess the status of arterial inflammation and fibrosis. |
| Change in level of cytokines | week 4, 12 and 24 | A cytokine panel are used to evaluate serum levels of cytokines in involved signaling pathways. |
| Changes in serum C reactive protein (CRP) | week 4, 12 and 24 | serum C reactive protein (CRP) is an indicator of systemic inflammation, will be reported in mg/L |
Countries
China
Contacts
Primary ContactShangyi Jin, MD
Outcome results
None listed