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

NCT06356740 | Not Yet Recruiting Phase 2

• 2 other identifiers: 69HCL22_08782023-508611-22-00
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 11

Brief 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).

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic lupus; Systemic Lupus Erythematosus; abacavir; lamivudine; nucleoside reverse transcriptase inhibitors

Outcome Measures

Primary Outcomes (1)

• 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)..

  At M6 (after 6 months of treatment)

Secondary Outcomes (12)

• percentage of patients maintaining LLDAS criteria

  until 12 months after randomisation

• number of relapses

  until 12 months after randomisation

• anti-native double-stranded DNA quantification

  until 12 months after randomisation

• anti-extractable nuclear antigens (anti-ENA) quantification

  until 12 months after randomisation

• interferon-α production quantification

  until 12 months after randomisation

Study Arms (2)

Abacavir 600 mg/lamivudine 300 mg

EXPERIMENTAL

Patients randomized to this group will take 1 tablet (600 mg lamivudine and 300 mg abacavir) once daily for 6 months in addition to their usual treatment.

Biological: Blood sample; Drug: Treatment :Abacavir 600 mg/lamivudine 300 mg; Other: Lupus Impact Tracker questionnaire

Control group (standard of care)

ACTIVE COMPARATOR

Patients randomized to this group will continue their usual treatment for lupus systemic.

Biological: Blood sample; Other: Lupus Impact Tracker questionnaire

Interventions

Blood sample BIOLOGICAL

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.

Abacavir 600 mg/lamivudine 300 mg; Control group (standard of care)

Treatment :Abacavir 600 mg/lamivudine 300 mg DRUG

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.

Abacavir 600 mg/lamivudine 300 mg

Lupus Impact Tracker questionnaire OTHER

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).

Abacavir 600 mg/lamivudine 300 mg; Control group (standard of care)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient affiliated to a social security scheme
• Free, informed and written consent signed by patient or parents/legal guardian

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (11)

Groupe Hospitalier Pellegrin-CHU de Bordeaux

Bordeaux, 33076, France

Location

Hôpital Femme-Mère-Enfant (HCL)

Bron, 69677, France

Location

CHU de Clermont-Ferrand - Hôpital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

CHU Nord de Grenoble - Albert Michallon

Grenoble, 38043, France

Location

Hôpital Claude Huriez

Lille, 59037, France

Location

Hôpital de la Croix-Rousse (HCL)

Lyon, 69004, France

Location

Hôpital Edouard Herriot (HCL)

Lyon, 69437, France

Location

Hôpital Necker-Enfants malades

Paris, 75015, France

Location

Hôpital Pitié-Salpêtrière

Paris, 75651, France

Location

Hôpital Lyon Sud (HCL)

Pierre-Bénite, 69310, France

Location

CHU de Saint-Etienne - Hôpital Nord

Saint-Priest-en-Jarez, 42270, France

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Blood Specimen Collection; Lamivudine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Central Study Contacts

Alexandre BELOT

CONTACT

04 27 85 61 26; Alexandre.belot@chu-lyon.fr

Samira PLASSART

CONTACT

04 27 85 54 42; Samira.plassart@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label randomized, controlled study with 2 parallel arms (Add-on treatment versus standard of care treatment)

Study Record Dates

• First Submitted: April 4, 2024
• First Posted: April 10, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 10, 2024

Record last verified: 2024-04

Locations

FR (11)