Randomised, controlled phase II proof-of-concept trial to assess the efficacy of abaCavIr/lamivudine treatment on the interferon signature in patients with systemic lupus erythematosus - PENCIL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Feb 2026 → ongoing

Decision date (initial)

2024-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2023-508611-22-00

ClinicalTrials.gov

NCT06356740

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the addition of the Abacavir/Lamivudine combination (Add-on) to standard care for 6 months, on the value of the interferon (IFN) transcriptome signature of patients with systemic lupus with low activity as defined by the LLDAS (Lupus Low Disease Activity State), in the 2 treatment arms, on the total population, on the paediatric population and on the adult population.

Secondary objectives 8

1. Assess maintenance of low clinical activity according to LLDAS criteria or remission at M6 and M12 in the intervention and no intervention arms.
2. To assess the effect of treatment on lupus biomarkers (anti-native double-stranded DNA, anti-NA, C3, C4, CH50 antibodies) and interferon-α production a. at M6 in the 2 arms b. at M12 in both arms
3. Evaluate the number of patients in the "Intervention" arm and the "No intervention" arm for whom the decrease in IFN signature is ≥ 50% at M6.
4. Evaluate the impact of treatment on the use of other treatments (including corticosteroids) in the "Intervention" arm and the "No intervention" arm at M6 and M12.
5. Assess quality of life (Lupus Impact Tracker™) at M6 and M12 in the "Intervention" arm and the "No intervention" arm.
6. Assess adherence to treatment (follow-up diary and telephone call at M3).
7. Assess treatment tolerance and safety
8. Quantifying HERV transcription

Conditions and MedDRA coding

systemic lupus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient ≥12 years old (weighing more than 25 kg) and ≤ 65 years old
2. Diagnosis of LS according to 2019 ACR (American College of rheumatology) / EULAR (European Ligue against Rheumatism) criteria (score >10)
3. Patient with LS in remission or with low clinical activity according to LLDAS criteria
4. or female patients (including sexually active adolescents) of childbearing age, effective contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) for the entire duration of treatment is required. A pregnancy test will be carried out at inclusion.
5. Patient affiliated to a social security scheme
6. Free, informed and written consent signed by the patient or his/her parents/legal guardian

Exclusion criteria 11

1. History of allergy or hypersensitivity to Abacavir, lamivudine or the excipients (tablet core: microcrystalline cellulose, crospovidone, magnesium stearate, colloidal anhydrous silica, talc; film coating: hypromellose, titanium dioxide (E171), macrogol, polysorbate 80)
2. Patients on anti-retroviral treatment
3. Patients with chronic HIV, HBV or HCV infection
4. Pregnant or breast-feeding woman
5. Patient treated with Lamivudine and/or Abacavir
6. Patient treated with a cytidine analogue
7. Patient receiving treatment containing Cladribine
8. Patient receiving treatment containing a trimethoprim/sulphamethoxazole combination (Bactrim)
9. Patients with renal impairment (creatinine clearance < 50 ml/min)
10. Patients with moderate or severe hepatic impairment (prothrombin level <50%)
11. Patient taking part in other interventional research involving medicinal products

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute variation in the interferon (IFN) signature between the start of treatment (M0) and after 6 months of treatment (M6) on the total population (then on the paediatric population then on the adult population). The IFN signature is measured from the transcriptomic expression of 6 IFN-inducible genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2 and SIGLEC)

Secondary endpoints 8

1. Maintenance of low clinical activity (LLDAS criteria) or remission will be assessed according to : a. The percentage of patients who maintained LLDAS criteria at M6 and M12 in the 2 arms b. the number of relapses and the time to relapse between M0 and M12 (collected continuously)
2. Evaluation of lupus biomarkers: anti-dsDNA, anti-ENA, C3, C4, CH50 fractions and interferon-α production between M0 and M6 and M0 and M12 in the 2 arms
3. Number of successful patients in each arm. Success is defined as a ≥50% decrease in IFN signature between M0 and M6
4. Cumulative dose of intravenous (IV) and oral corticosteroids from M0 to M6 and from M6 to M12
5. Difference between M0 and M6 and M0 and M12 in Lupus Impact Tracker™ score in the 2 arms
6. Monitoring of treatment adherence in the 2 arms (follow-up diary + telephone call): number of "missed" doses between M0 and M6 and reasons for missed doses.
7. AEs and SAEs between M0 and M12 in the 2 arms
8. Difference in human endogenous retrovirus (HERV) copy number in the 2 arms at M6 and M12 compared with M0. A comparison between the groups will be carried out

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Alexandre BELOT

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Alexandre BELOT

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications