Combination of Biologic and Anti-obesity Therapies in Psoriatic Arthritis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- Correlation of molecular changes in biopsies (skin, synovial and adipose) with weight loss
研究概览
简要总结
This is a trial to find out how weight loss (achieved by the use of tirzepatide) or ixekizumab treatment affects the characteristics of skin, joint and fat tissues in patients with Psoriatic Arthritis, Psoriasis and obesity/overweight BMI >=27.
Participants will be allocated either Tirzepatide, Ixekizumab or both. Samples of joint tissue, fat and skin will be taken at the start of the study and week 12. Blood and urine samples will also be taken.
The primary objective will be to assess the changes seen in the joint, fat and skin tissue samples 12 weeks after starting the medications (additional analysis will be done on the optional 36 week samples).
Secondary objectives will be
- To assess the changes seen in blood 4, 12, 36 and 52 weeks after starting the medication.
- To compare the changes seen in tissue and blood between Ixekizumab and Tirzepatide/Weight loss.
- To see how the changes seen in the tissue relate to weight loss.
详细描述
This is a trial to find out how weight loss (achieved by the use of tirzepatide) or ixekizumab treatment affects the characteristics of skin, joint and adipose tissues in patients with Psoriatic Arthritis, Psoriasis and obesity/overweight BMI >=27.
Patients will be randomised to three groups- tirzeparatide only, ixekizumab only or both drugs.
They will have an ultrasound guided synovial biopsy, a 4mm punch skin biopsy, alea skin tape sampling and a needle aspiration fat biopsy at baseline, and then be followed up for 52 weeks.
Disease activity will be monitored throughout the trial (both examination and clinical questionnaires), and participants in the tirzepatide only group not in PsA minimal disease activity (with > 1 swollen joint, >1 tender entheseal point or PASI >1/BSA >3%) at weeks 12, 24 or 36 will be offered the addition of Ixekizumab.
As well as the biopsies, bloods and urine will be taken at weeks 0, 4, 12, 24, and 52; urine samples taken at weeks 0, 12 and 36; and an additional alea skin tape sample at week 4.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
No masking is involved
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years and <=75 years
- •Have a documented diagnosis of PsA for at least 6 months AND fulfil the CASPAR criteria (Defined as >=3 points)
- •Have active PsA defined as >=3 swollen and >=3 tender joints (dactylitis counts as a swollen joint).
- •Have a BMI >= 27 kg/m^2
- •Have at least one affected joint amenable to ultrasound-guided synovial biopsy (and must undergo successful synovial biopsy prior to randomisation)
- •Have at least one psoriatic plaque amenable to biopsy (up to a maximum of 5 participants per treatment arm can be recruited without skin biopsy if no suitable lesion
- •Capable of giving signed informed consent
- •Willing and able to participate in the study and undergo synovial, adipose and skin (if appropriate) biopsies (under local anaesthetic) on at least 2 occasions
排除标准
- •Prior/Concomitant Therapy:
- •Previous treatment with tirzepatide or any GLP-1 receptor agonist.
- •Previous treatment with Ixekizumab.
- •Previous treatment with BOTH secukinumab AND Bimekizumab. [note: Previous treatment with one of EITHER secukinumab OR Bimekizumab for PsA/psoriasis is allowed PROVIDED: i) Last dose was >6months before baseline AND ii) Therapy was not stopped due to an IL-17-related side effect OR due to complete primary lack of response.
- •Previous treatment with rituximab.
- •Failed >3 classes of advanced therapies (regardless of given for PsA or psoriasis), including but not limited to:
- •TNF inhibitors (adalimumab, etanercept, certolizumab, golimumab, and infliximab)
- •IL-12/23 inhibitors (ustekinumab)
- •IL-23 inhibitors (guselkumab and risankizumab)
- •IL-17 Inhibitors (secukinumab or bimekizumab)
- •Selective co-stimulation modulators (abatacept)
- •Janus Kinase or tyrosine kinase 2 inhibitors (tofacitinib, upadacitinib and deucravacitinib) Note: Prior exposure to phosphodiesterase-4 inhibitors, such as apremilast and conventional synthetic DMARDs, such as methotrexate, are not considered as advanced therapies.
- •If currently receiving conventional DMARDs, or apremilast, must have been treated for at least 12 weeks prior to first biopsy visit and on a stable dose for at least 8 weeks prior to first biopsy visit.
- •Use or oral, intra-articular, IM or IV corticosteroids 4 weeks prior to first biopsy visit or anticipated/planned prior to the week 12 biopsy visit.
- •Topical steroids within 2 weeks of first biopsy visit (participants on topical corticosteroids at baseline willing to leave these off 2 weeks prior to biopsy will be eligible).
- •Live, attenuated or recombinant vaccination within 1 month prior to screening visit or planned before the 12 week visit.
- •Contraindication to local anaesthetics (lidocaine/similar) used for biopsies
- •Antiplatelet or anticoagulant therapy that cannot be safely interrupted:
- •Clopidogrel or other antiplatelet therapies (note: aspirin is not an exclusion)
- •Vitamin K antagonists (including but not limited to warfarin)
- •Direct inhibitors of thrombin (e.g. dabigatran)
- •Factor Xa inhibitors (e.g. rivaroxaban, apixaban)
- •Heparins (including low-molecular weight heparins (LMWH)
- •Previous treatment with insulin (exception: Use of insulin for gestational diabetes or short-term use (less than 14 days) for acute conditions, such as acute illness, hospitalisation or elective surgery).
- •Medical Conditions:
- •Diagnosis of type 1 diabetes or insulin treated type 2 diabetes.
- •History of severe hypoglycaemia and/or hypoglycaemia unawareness within the 6 months prior to screening.
- •History of ketoacidosis or hyperosmolar state or coma in the last year
- •Any current or past diagnosis of:
- •proliferative diabetic retinopathy, or
- •diabetic maculopathy, or
- •non-proliferative diabetic retinopathy that requires treatment.
- •Have a self-reported change in body weight greater than 5% (gain or loss) within 3 months prior to screening.
- •Prior or planned surgical treatment for obesity, such as gastric bypass (bariatric) surgery or restrictive bariatric surgery (excluding liposuction or abdominoplasty if performed more than 1 year prior to screening).
- •Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome type
- •History of IBD (Crohn's disease or ulcerative colitis).
- •Known clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction); or chronically take drugs that directly effect gastroparesis.
- •History of chronic or acute pancreatitis.
- •Renal Impairment with estimated glomerular filtration rate (GFR) of less than or equal to 30ml/min/1.73m^
- •A diagnosis or history of malignant disease within 5 years prior to baseline visit, with the following exceptions:
- •Basal cell and squamous epithelial carcinomas of the skin that have been resected, with no evidence of metastatic disease for 3 years and 2 years, respectively.
- •cervical carcinoma in situ, with no evidence of recurrence within 3 years.
- •History of any other condition (such as known drug, alcohol abuse, or psychiatric disorder) that, in the opinion of the investigator, may preclude the participant from following and completing the study.
- •History of significant active or unstable major depressive disorder (MDD), suicidal ideation, or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years.
- •Note: Participants with MDD or generalised anxiety disorder whose disease state is considered stable for the past year and expected to remain stable throughout the course of the study, in the opinion of the investigator, may be considered for inclusion if they are not on excluded medications.
- •Are, in the judgement of the investigator, actively suicidal or deemed to be at significant risk for suicide.
- •Diagnosis of other inflammatory arthritis, such as rheumatoid arthritis, ankylosing spondylitis, reactive arthritis, gout, or enteropathic arthritis.
- •Active infection at screening.
- •Have had any of the following types of infection within 3 months prior to screening or develops any of the following infections before the baseline visit:
- •Serious (requiring hospitalisation, or intravenous or equivalent oral antibiotic treatment, or both).
- 另有 29 项未显示
研究组 & 干预措施
Tirzepatide group
干预措施: Tirzepatide (Drug)
Combined tirzepatide and ixekizumab
干预措施: Ixekizumab (Drug)
Ixekizumab group
干预措施: Ixekizumab (Drug)
Combined tirzepatide and ixekizumab
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Correlation of molecular changes in biopsies (skin, synovial and adipose) with weight loss
时间窗: 12 weeks
Percentage change in weight (in kg) from baseline will be correlated with changes in molecular markers in tissues (synovium, skin and adipose). This is an experimental medicine (and not efficacy) study that will utilise a range of advanced spatial and other tissue omics to measure molecular markers in these tissues at baseline and 12 weeks. It is not possible or appropriate to specify a single biomarker or measure for this.
次要结局
- Correlation of changes in molecular signatures in the peripheral blood with weight loss.(12 weeks)
- Comparison of molecular changes in biopsies (skin, synovial and adipose) and in the peripheral blood with weight loss versus those with immunomodulation by IL-17A inhibition.(12 weeks)