Efficacy and Tolerance of Abacavir/Lamivudine Treatment in Patients With Systemic Lupus Erythematosus - Trial NCT06356740

Timeline & Enrollment

Primary Outcome

Absolute variation in interferon signature (IFN)

Summary

Systemic lupus (SL) is a rare chronic autoimmune disease characterized by the production of
 autoantibodies directed against nuclear antigens, particularly native double-stranded
 deoxyribonucleic acid (DNA), and excessive production of antiviral cytokines: type I
 interferons, particularly interferon alpha (IFN-α). IFN-α production results from the
 excessive detection of nucleic acids (DNA or Ribonucleic Acid (RNA)) by endosomal or
 intracytoplasmic receptors that are capable of inducing interferon production. The precise
 mechanisms of cytoplasmic sensor activation remain unknown; however, recent work in the field
 of interferonopathies suggests a role for human endogenous retroviruses (HERVs). HERVs are
 remnants of ancient infections caused by exogenous retroviruses integrated into the genome
 during evolution and represent 8% of the human genome.Several studies have suggested a role
 for HERVs in the development and maintenance of an excessive immune response in lupus
 patients and other autoimmune diseases by affecting the type I interferons (I IFN) signalling
 pathway.
 
 To date, none of the approved immunosuppressive drugs for Systemic Lupus Erythematosus (SLE)
 have been shown to be effective in the background treatment of SL or in preventing relapse.
 Consequently, there is an urgent need to identify new molecules and therapeutic avenues for
 disease-modifying therapies.
 
 In this study, an innovative therapeutic strategy using a combination of nucleoside reverse
 transcriptase inhibitors (NRTIs), abacavir/lamivudine, is proposed to treat SLE. Thus, we
 propose a pilot Phase II, randomized, open-label study using NRTIs in patients with SL in
 remission or with low clinical activity, and evaluating a biological endpoint (IFN
 signature), which is a direct proxy for the drug's expected effect.
 
 The main objective is to compare the addition of Abacavir/Lamivudine (Add-on) to standard
 care for 6 months, on the value of the interferon (IFN) transcriptomic signature of patients
 with systemic lupus with low activity as defined by the Lupus Low Disease Activity State
 (LLDAS).

ICD-10 Classifications