NCT04474847招募中3 期
A Randomized Double-Blind, Placebo Controlled Trial of Abatacept (CTLA4-Ig) in Giant Cell Arteritis (ABAGART)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 11
- 主要终点
- The proportion of participants in remission of those randomized to abatacept as compared to placebo.
研究概览
简要总结
This randomized, double-blind, placebo-controlled trial will seek to determine the efficacy of abatacept in GCA. To examine this objective, 62 eligible patients who have newly diagnosed or relapsing GCA within 8 weeks prior to screening will be randomized at a 1:1 ratio to receive subcutaneous abatacept 125mg/week or placebo. Patients who achieve remission will remain on their blinded assignment for 12 months at which time abatacept/placebo will be stopped.
Patients who do not achieve remission by Month 3, who experience a relapse within the first 12 months will have the option of receiving open-label abatacept for a maximum of 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA
- •A patient will be said to have GCA by meeting 3 of 5 of the following modified ACR criteria for the classification of GCA in which 1 of the 3 must consist of criteria 4 or 5:
- •Age at disease onset ≥ 50 years.
- •New onset or new type of localized pain in the head.
- •ESR of > 40 mm in the first hour by the Westergren method or CRP measurement above the laboratory normal limit.
- •Temporal artery abnormality (i.e., temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries).
- •Temporal artery or large vessel biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cell or an abnormal temporal artery ultrasound showing features consistent with active giant cell arteritis ("halo sign") or characteristic changes of large vessel stenosis or aneurysm by arteriography.
- •GCA with evidence of active disease (defined below) present within the past 8 weeks.
- •They must be willing and able to comply with treatment and follow-up procedures.
- •Both women and men who are of child-bearing potential must be willing to use an effective means of birth control while receiving treatment through this study. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception.
- •They must be willing and able to provide written informed consent.
排除标准
- •Evidence of a recent acute infection defined as:
- •Any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics.
- •Any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy.
- •Patients with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.).
- •Patients with a history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening.
- •Patients with a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis).
- •Patients with a history of primary immunodeficiency.
- •Patients at risk for tuberculosis (TB) defined as follows:
- •Current clinical, radiographic or laboratory evidence of active TB, even if currently being treated. Chest x-rays (posterior/anterior and lateral) obtained within the 6 months prior to screening and TB testing (IFN-gamma release assay or PPD) performed in the past month prior to screening will be accepted; however, a copy of the reports must be placed in the participant binder.
- •A history of active TB unless there is documentation that the patient had received prior anti-TB treatment that was appropriate in duration and type according to local health authority guidelines.
- •Patients with a positive TB screening test indicative of latent TB will not be eligible for the study unless they:
- •i. Have no evidence of current TB based on chest x-ray performed during the screening period and by history and physical exam, and ii. They are currently being treated for latent TB or the site has documentation of successful prior treatment of latent TB. Treatment regimens should be dictated by local guidelines as long as the treatment dose and duration meet or exceed local health authority guidelines. If permitted by local guidelines regarding treatment with biologic medications, patients with latent TB may be randomized prior to completion of treatment as long as they have completed at least 4 weeks of treatment and they have no evidence of current TB on chest x-ray at screening.
- •Patients who are pregnant or who are nursing infants.
- •Inability to comply with study guidelines.
- •Cytopenia: platelet count <80,000/mm3, total White Blood Count (WBC) < 3,000/mm3 (3 x 109/L) absolute neutrophil <1500/mm3, hematocrit < 20%.
- •Renal insufficiency defined by a creatinine clearance of less than or equal to 20 ml/min.
- •AST or ALT > 3 times above normal laboratory range.
- •Other severe, progressive, or uncontrolled disease that in the investigator's opinion could prevent a patient from fulfilling the study requirements or that would increase the risk of study participation.
- •Patients who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
- •Receipt of an investigational agent or device within 30 days prior to enrollment.
- •A live vaccination within 3 months before randomization.
- •Patients on non-biologic immunosuppressants must discontinue these medications before randomization (azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, hydroxychloroquine, cyclosporin, tacrolimus, or other conventional immunosuppressive agent).
- •Patients who had received an alkylating agent such as cyclophosphamide must discontinue these medications at least 8 weeks before randomization.
- •Patients who have been treated within 4 weeks of randomization with etanercept or within 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.
- •Patients who have been treated within 8 weeks of randomization with anti-IL-6 agents (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.
- •Patients who have been treated within 4 weeks of randomization with anakinra.
- •Patients who have received prior treatment with rituximab within the past 6 months prior to randomization.
- •Patients who have received prior treatment with abatacept or CTLA4-Ig.
- •Patients who will require oral or IV glucocorticoid treatment during the trial for conditions other than GCA.
- •Hypersensitivity to abatacept and/or its excipients.
- •Presence of any of the following disease processes:
- •Takayasu arteritis
- •Granulomatosis with polyangiitis
- •Microscopic polyangiitis
- •Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
- •Polyarteritis nodosa
- •Cogan's syndrome
- •Behçet's disease
- •Sarcoidosis
- •Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics vasculitis
- •Cryoglobulinemic vasculitis
- •Systemic lupus erythematosus
- •Rheumatoid arthritis
- •Mixed connective tissue disease or any overlap autoimmune syndrome
研究组 & 干预措施
Blinded Placebo
Placebo Comparator
Participants will receive blinded placebo. Placebo will be administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.
干预措施: Placebo (Drug)
Blinded Abatacept
Experimental
Participants will receive blinded abatacept 125 mg administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.
干预措施: Abatacept (Drug)
结局指标
主要结局
The proportion of participants in remission of those randomized to abatacept as compared to placebo.
时间窗: 12 months
Remission is defined as the absence of clinical or imaging features of active disease
次要结局
- Safety of abatacept in GCA(12 months)
- Health-related quality of life in those treated with abatacept versus placebo: PROMIS questionnaire(12 months)
- Health-related quality of life in those treated with abatacept versus placebo: SF-36(12 months)
- Duration of glucocorticoid-free remission from Month 6 to Month 12(6 months)
研究者
研究点 (11)
Loading locations...
相似试验
已完成
3 期
Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) PatientsPhenylketonuriaNCT01114737BioMarin Pharmaceutical206
Unknown
3 期
Efficacy of Atorvastatin in Chronic Subdural HaematomaChronic Subdural HematomaNCT03956368Chinese University of Hong Kong690
已完成
2 期
Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled AsthmaAsthmaNCT05251259AstraZeneca670
撤回
3 期
Study to Evaluate the Safety and EffIcacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry DiseaseFabry DiseaseNCT02921620Protalix
终止
2 期
A Clinical Trial to Evaluate PCS499 in Treating Ulcerations in Patients Who Have Necrobiosis LipoidicaNecrobiosis LipoidicaNCT04800562Processa Pharmaceuticals4