Randomised, controlled phase II proof-of-concept trial to assess the efficacy of abaCavIr/lamivudine treatment on the interferon signature in patients with systemic lupus erythematosus - PENCIL
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 8
- 主要终点
- Absolute variation in the interferon (IFN) signature between the start of treatment (M0) and after 6 months of treatment (M6) on the total population (then on the paediatric population then on the adult population). The IFN signature is measured from the transcriptomic expression of 6 IFN-inducible genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2 and SIGLEC)
研究概览
简要总结
To compare the addition of the Abacavir/Lamivudine combination (Add-on) to standard care for 6 months, on the value of the interferon (IFN) transcriptome signature of patients with systemic lupus with low activity as defined by the LLDAS (Lupus Low Disease Activity State), in the 2 treatment arms, on the total population, on the paediatric population and on the adult population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Abacavir/lamivudine
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Patient ≥12 years old (weighing more than 25 kg) and ≤ 65 years old
- •Diagnosis of LS according to 2019 ACR (American College of rheumatology) / EULAR (European Ligue against Rheumatism) criteria (score >10)
- •Patient with LS in remission or with low clinical activity according to LLDAS criteria
- •or female patients (including sexually active adolescents) of childbearing age, effective contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) for the entire duration of treatment is required. A pregnancy test will be carried out at inclusion.
- •Patient affiliated to a social security scheme
- •Free, informed and written consent signed by the patient or his/her parents/legal guardian
排除标准
- •History of allergy or hypersensitivity to Abacavir, lamivudine or the excipients (tablet core: microcrystalline cellulose, crospovidone, magnesium stearate, colloidal anhydrous silica, talc; film coating: hypromellose, titanium dioxide (E171), macrogol, polysorbate 80)
- •Patients with moderate or severe hepatic impairment (prothrombin level <50%)
- •Patient taking part in other interventional research involving medicinal products
- •Patients on anti-retroviral treatment
- •Patients with chronic HIV, HBV or HCV infection
- •Pregnant or breast-feeding woman
- •Patient treated with Lamivudine and/or Abacavir
- •Patient treated with a cytidine analogue
- •Patient receiving treatment containing Cladribine
- •Patient receiving treatment containing a trimethoprim/sulphamethoxazole combination (Bactrim)
- •Patients with renal impairment (creatinine clearance < 50 ml/min)
结局指标
主要结局
Absolute variation in the interferon (IFN) signature between the start of treatment (M0) and after 6 months of treatment (M6) on the total population (then on the paediatric population then on the adult population). The IFN signature is measured from the transcriptomic expression of 6 IFN-inducible genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2 and SIGLEC)
Absolute variation in the interferon (IFN) signature between the start of treatment (M0) and after 6 months of treatment (M6) on the total population (then on the paediatric population then on the adult population). The IFN signature is measured from the transcriptomic expression of 6 IFN-inducible genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2 and SIGLEC)
次要结局
- Maintenance of low clinical activity (LLDAS criteria) or remission will be assessed according to : a. The percentage of patients who maintained LLDAS criteria at M6 and M12 in the 2 arms b. the number of relapses and the time to relapse between M0 and M12 (collected continuously)
- Evaluation of lupus biomarkers: anti-dsDNA, anti-ENA, C3, C4, CH50 fractions and interferon-α production between M0 and M6 and M0 and M12 in the 2 arms
- Number of successful patients in each arm. Success is defined as a ≥50% decrease in IFN signature between M0 and M6
- Cumulative dose of intravenous (IV) and oral corticosteroids from M0 to M6 and from M6 to M12
- Difference between M0 and M6 and M0 and M12 in Lupus Impact Tracker™ score in the 2 arms
- Monitoring of treatment adherence in the 2 arms (follow-up diary + telephone call): number of "missed" doses between M0 and M6 and reasons for missed doses.
- AEs and SAEs between M0 and M12 in the 2 arms
- Difference in human endogenous retrovirus (HERV) copy number in the 2 arms at M6 and M12 compared with M0. A comparison between the groups will be carried out
研究者
Pr Alexandre BELOT
Scientific
Hospices Civils De Lyon