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

Civil Hospices of Lyon

Status and phase: Not yet enrolling; Phase 2

Conditions: Systemic Lupus Erythematosus

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06356740

2023-508611-22-00

69HCL22_0878

Details and patient eligibility

About

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).

Enrollment: 70 estimated patients

Sex: All

Ages: 12 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Abacavir 600 mg/lamivudine 300 mg

Experimental group

Description:

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.

Treatment:

Other: Lupus Impact Tracker questionnaire

Biological: Blood sample

Drug: Treatment :Abacavir 600 mg/lamivudine 300 mg

Control group (standard of care)

Active Comparator group

Description:

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

Treatment:

Other: Lupus Impact Tracker questionnaire

Biological: Blood sample