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

Phase 2Not Yet RecruitingNCT06356740

Hospices Civils de Lyon70 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Blood sampleBIOLOGICAL

blood test to assess : * human leukocyte antigen (HLA)-B\*5701 status to identify risk of allergy or hypersensitivity to abacavir (the study treatment) * IFN-signature ans IFN-alpha dosage * human immunodeficiency virus (HIV), hepatitis B virus (HBV) and Hepatitis C virus (HCV) serologies * Human chorionic gonadotropin (βHCG) * HERVs dosage A biological collection will also be created. The total volume of blood collected specifically for the research for the entire duration of the study is 62.5 millilitre (mL) maximum.

Treatment :Abacavir 600 mg/lamivudine 300 mgDRUG

Patients randomised to the experimental arm will be required to take 1 tablet (600 mg lamivudine and 300 mg abacavir) once daily for 6 months in addition to their usual treatment.

Lupus Impact Tracker questionnaireOTHER

Patients will be asked to complete the Lupus Impact Tracker questionnaire at visit V1 (randomisation visit), visit 3 (at 6 months of treatment) and visit 4 (12 months after visit 1).

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient ≥12 years old (weighing more than 25 kg) and ≤ 65 years old * Diagnosis of SL according to 2019 American College of rheumatology (ACR) / European Ligue against Rheumatism (EULAR) criteria (score \>10) * Patient with SL in remission or with low clinical activity according to LLDAS disease criteria * For patients (including sexually active adolescents) of childbearing age, effective contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm, sponge with spermicide, or condom) for the entire duration of treatment is required. Pregnancy tests will be performed according to the inclusion criteria. * Patient affiliated to a social security scheme * Free, informed and written consent signed by patient or parents/legal guardian Exclusion Criteria: * Patients with HLA-B\*5701 status (risk of allergy or hypersensitivity to Abacavir) * History of allergy or hypersensitivity to abacavir, lamivudine, or excipients (tablet core: microcrystalline cellulose, crospovidone, magnesium stearate, colloidal anhydrous silica, talc; film coating: hypromellose, titanium dioxide (E171), macrogol, polysorbate 80). * Patients on anti-retroviral therapy * 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 analog * Patient on treatment containing Cladribine * Patient on treatment containing a trimethoprim/sulfamethoxazole combination * Patients with renal insufficiency (creatinine clearance \< 50 ml/min) * Patients with moderate or severe hepatic impairment (prothrombin level \<50%) * Patient participating in other interventional drug research

Locations (11)

Groupe Hospitalier Pellegrin-CHU de Bordeaux

Bordeaux, France

Hôpital Femme-Mère-Enfant (HCL)

Bron, France

CHU de Clermont-Ferrand - Hôpital Gabriel Montpied

Clermont-Ferrand, France

CHU Nord de Grenoble - Albert Michallon

Grenoble, France

Hôpital Claude Huriez

Lille, France

Hôpital de la Croix-Rousse (HCL)

Lyon, France

Hôpital Edouard Herriot (HCL)

Lyon, France

Hôpital Necker-Enfants malades

Paris, France

Hôpital Pitié-Salpêtrière

Paris, France

Hôpital Lyon Sud (HCL)

Pierre-Bénite, France

...and 1 more locations

Outcomes

Primary Outcomes

Absolute variation in interferon signature (IFN)

Absolute change in interferon (IFN) signature will be assessed between the start of treatment (M0) and after 6 months of treatment (M6) in the total population (then in the pediatric population, then in the adult population)..

Time frame: At M6 (after 6 months of treatment)