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

Phase 2

Not yet recruiting

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

Inclusion Criteria

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

Exclusion Criteria

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, France
Zahir AMOURA
Site contact
0142178001
zahir.amoura@aphp.fr