protocolSection identificationModule nctId: NCT06356740, orgStudyIdInfo id: 69HCL22_0878, secondaryIdInfos id: 2023-508611-22-00, type: CTIS, briefTitle: Efficacy and Tolerance of Abacavir/Lamivudine Treatment in Patients With Systemic Lupus Erythematosus, acronym: PENCIL, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-09-01, primaryCompletionDateStruct date: 2028-11-01, completionDateStruct date: 2029-06-01, studyFirstPostDateStruct date: 2024-04-10, lastUpdatePostDateStruct date: 2024-04-10, sponsorCollaboratorsModule leadSponsor name: Hospices Civils de Lyon, class: OTHER, descriptionModule briefSummary: 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)., conditionsModule conditions: Systemic Lupus Erythematosus, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Open-label randomized, controlled study with 2 parallel arms (Add-on treatment versus standard of care treatment), primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 70, type: ESTIMATED, armsInterventionsModule interventions name: Blood sample, interventions name: Treatment :Abacavir 600 mg/lamivudine 300 mg, interventions name: Lupus Impact Tracker questionnaire, outcomesModule primaryOutcomes measure: Absolute variation in interferon signature (IFN), secondaryOutcomes measure: percentage of patients maintaining LLDAS criteria, secondaryOutcomes measure: number of relapses, secondaryOutcomes measure: anti-native double-stranded DNA quantification, secondaryOutcomes measure: anti-extractable nuclear antigens (anti-ENA) quantification, secondaryOutcomes measure: interferon-α production quantification, secondaryOutcomes measure: Number of successful patients, secondaryOutcomes measure: Cumulative dose of intravenous (IV) corticosteroids, secondaryOutcomes measure: Lupus Impact Tracker questionnaire score, secondaryOutcomes measure: number of missed treatment, secondaryOutcomes measure: number of adverse event (AE), secondaryOutcomes measure: number of serious adverse event (SAE), secondaryOutcomes measure: HERVs transcription quantification, eligibilityModule sex: ALL, minimumAge: 12 Years, maximumAge: 65 Years, stdAges: CHILD, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Groupe Hospitalier Pellegrin-CHU de Bordeaux, city: Bordeaux, zip: 33076, country: France, contacts name: Christophe RICHEZ, MD, PhD, role: CONTACT, phone: 05 56 79 56 79, phoneExt: +33, email: christophe.richez@chu-bordeaux.fr, contacts name: Christophe RICHEZ, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 44.84044, lon: -0.5805, locations facility: Hôpital Femme-Mère-Enfant (HCL), city: Bron, zip: 69677, country: France, contacts name: Alexandre BELOT, MD, PhD, role: CONTACT, phone: 04 27 85 61 26, phoneExt: +33, email: Alexandre.belot@chu-lyon.fr, contacts name: Alexandre BELOT, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.73333, lon: 4.91667, locations facility: CHU de Clermont-Ferrand - Hôpital Gabriel Montpied, city: Clermont-Ferrand, zip: 63003, country: France, contacts name: Marc ANDRE, MD, PhD, role: CONTACT, phone: 0473751440, phoneExt: +33, email: mandre@chu-clermontferrand.fr, contacts name: Marc ANDRE, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.77966, lon: 3.08628, locations facility: CHU Nord de Grenoble - Albert Michallon, city: Grenoble, zip: 38043, country: France, contacts name: Laurence BOUILLET, MD, PhD, role: CONTACT, phone: 04 76 76 76 40, phoneExt: +33, email: lbouillet@chu-grenoble.fr, contacts name: Laurence BOUILLET, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.16667, lon: 5.71667, locations facility: Hôpital Claude Huriez, city: Lille, zip: 59037, country: France, contacts name: Éric HACHULLA, MD, PhD, role: CONTACT, phone: 03 20 44 56 50, phoneExt: +33, email: eric.hachulla@chru-lille.fr, contacts name: Éric HACHULLA, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.63297, lon: 3.05858, locations facility: Hôpital de la Croix-Rousse (HCL), city: Lyon, zip: 69004, country: France, contacts name: Yvan JAMILLOUX, MD, PhD, role: CONTACT, phone: 0426732636, phoneExt: +33, email: yvan.jamilloux@chu-lyon.fr, contacts name: Yvan JAMILLOUX, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.74848, lon: 4.84669, locations facility: Hôpital Edouard Herriot (HCL), city: Lyon, zip: 69437, country: France, contacts name: Thomas BARBA, MD, role: CONTACT, phone: 0472119583, phoneExt: +33, email: thomas.barba@chu-lyon.fr, contacts name: Thomas BARBA, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.74848, lon: 4.84669, locations facility: Hôpital Necker-Enfants malades, city: Paris, zip: 75015, country: France, contacts name: Brigitte BADER-MEUNIER, MD, role: CONTACT, phone: 0144494332, phoneExt: +33, email: brigitte.bader-meunier@aphp.fr, contacts name: Brigitte BADER-MEUNIER, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Hôpital Pitié-Salpêtrière, city: Paris, zip: 75651, country: France, contacts name: Zahir AMOURA, MD, PhD, role: CONTACT, phone: 01 42 17 80 01, phoneExt: +33, email: zahir.amoura@aphp.fr, contacts name: Zahir AMOURA, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Hôpital Lyon Sud (HCL), city: Pierre-Bénite, zip: 69310, country: France, contacts name: Mael Richard, MD, role: CONTACT, phone: 0478861352, phoneExt: +33, email: mael.richard@chu-lyon.fr, contacts name: Mael Richard, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.7009, lon: 4.82511, locations facility: CHU de Saint-Etienne - Hôpital Nord, city: Saint-Priest-en-Jarez, zip: 42270, country: France, contacts name: Martin KILLIAN, MD, PhD, role: CONTACT, phone: 04 77 82 91 79, phoneExt: +33, email: martin.killian@chu-st-etienne.fr, contacts name: Martin KILLIAN, MD, PhD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.47501, lon: 4.37614, hasResults: False