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
- Conditions
- systemic lupus
- Registration Number
- 2023-508611-22-00
- Lead Sponsor
- Hospices Civils De Lyon
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 72
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
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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)
- Secondary Outcome Measures
Name Time Method 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) 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 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 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 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 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. 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 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 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
Trial Locations
- Locations (8)
Assistance Publique Hopitaux De Paris
🇫🇷Paris, France
Hospices Civils De Lyon
🇫🇷Pierre-Benite, France
Centre Hospitalier Universitaire Grenoble Alpes
🇫🇷Grenoble Cedex 9, France
University Hospital Of Clermont-Ferrand
🇫🇷Clermont Ferrand Cedex 1, France
Hopital Necker Enfants Malades
🇫🇷Paris, France
Centre Hospitalier Universitaire De Saint Etienne
🇫🇷Saint Priest En Jarez, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille Cedex, France
Centre Hospitalier Universitaire De Bordeaux
🇫🇷Bordeaux, France
Assistance Publique Hopitaux De Paris🇫🇷Paris, FranceZahir AMOURASite contact0142178001zahir.amoura@aphp.fr