Clinical trial NCT01738360: Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE) (Protocol LUPSENIC)
Official title: Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Systemic Lupus
Keywords: Arsenic trioxide
Systemic Lupus
clinically
biologically active
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Medsenic Company
First posted: 2012-11-30
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary objectives :

* To investigate the safety and the tolerability of ATO by IV infusions to patients with SLE,
* To determine the maximum tolerated dose of ATO.

Secondary objectives :

* Evaluation of the clinical and biological response of the SLE to ATO,
* Time of relapse in case of positive response,
* Determination of the efficacy,
* Pharmacokinetic study of ATO.


Eligibility criteria: Inclusion Criteria:

* Systemic Lupus meeting the ACR (American College of Rheumatology) criteria, progressive either SLEDAI activity score ≥ 4, despite a corticosteroid therapy ≥ 10 mg / d associated with hydroxychloroquine (in the absence of contraindication or intolerance) and / or an immunosuppressive treatment at a stable dose,
* Insured,
* Availability for hospitalization required by the protocol (conventional and daily hospitalizations).

Exclusion Criteria:

* Inability to give their signed informed consent form,
* Performans status \> 2
* QTcorrected space before treatment \> 0.45 seconds
* Hemoglobin less than 11g/dL
* Neutrophils rate below 1 200 / mm3
* Platelets rate below 100 Giga / mm3
* Previous history of arrhythmia or heart rhythm disorder or other rhythm trouble by referring cardiologist
* Heart disorder (progressive pericarditis, valvular disease, ...) according to cardiologist
* Family previous history of arrhythmias
* Taking drugs that potentially prolong the QT
* Hypersensitivity to the active substance of Trisenox® or any of the excipients
* Serum potassium ≤ 4 milliequivalent / L
* Magnesemia ≤ 1,8 mg / dl
* Increase corticosteroids beyond 20 mg / day within 15 days before inclusion
* Immunosuppressive treatments, thalidomide introduced within the last 3 months
* Biotherapy (rituximab, belimumab, ...) introduced within 6 months prior to inclusion
* Pregnancy or lactation
* For women of childbearing age, men and their partner : unless effective contraception for the duration of participation in the study that is 7 months
* Creatinine clearance \<50 ml / min,
* Hepatocellular insufficiency (TP \<50%), and / or AST (aspartate aminotransferase) / ALT (alanine aminotransferase) / ALP (alkaline phosphatase) \> 2N
* HBsAg positive, DNA detectable HbS
* Infection with HIV, HBV (hepatitis B virus) or HCV (hepatitis C virus)
* Renal or progressive central neurological impairment with possible alternative therapeutic (to be discussed with the principal investigator and scientific board meeting)
* Peripheral neuropathy
* Unweaned alcoholism
* Minor
* Patients older than 65 years
* Patient having been professionally exposed to arsenic (cleaning electronic circuits for example)
* Guardianship patients

Primary outcomes:
measure: Cardiac adverse events whatever grade and any adverse event of grade 3 or 4
timeFrame: 30 days after the last infusion
Secondary outcomes:
measure: Composite response of SLE
timeFrame: 30 months
measure: Anti-nuclear antibodies (ANA).
timeFrame: 30 months
measure: Anti-native DNA
timeFrame: 30 months
measure: C3 complement
timeFrame: 30 monhs
measure: C4 complement
timeFrame: 30 months
measure: Sedimentation rate
timeFrame: 30 months
measure: Serum creatinine
timeFrame: 30 months
measure: Proteinuria/creatinuria ratio
timeFrame: 30 months
measure: Serum protein electrophoresis
timeFrame: 30 months
measure: Quantitation of immunoglobulins
timeFrame: 30 months
measure: Quality of life
timeFrame: 30 months
measure: Steroids
timeFrame: 30 months
measure: Immunosuppressive treatments
timeFrame: 30 months
measure: Response time
timeFrame: 30 months
measure: Time to relapse
timeFrame: 30 months
measure: Blood test of arsenic
timeFrame: D1, D2, D3, D4, D8, D11, D15, D18, D22 and D25 (before and after each infusion)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Lille
country: France
facility: CHRU de Lille
city: Marseille
country: France
facility: CHU de Marseille
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: AP-HP - la Pitié-Salpétrière
city: Strasbourg
country: France
facility: CHRU de Strasbourg
Study officials:
affiliation: Nantes University Hospital
name: Mohamed HAMIDOU, Profesor
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HP - La Pitié-Salpétrière
name: Zahir AMOURA, Profesor
role: STUDY_CHAIR
affiliation: CHRU de Strasbourg
name: Jean SIBILIA, Profesor
role: STUDY_CHAIR
affiliation: University Hospital, Bordeaux
name: Jean-François VIALLARD, Profesor
role: STUDY_CHAIR
affiliation: CHU de Marseille
name: Nicolas SCHLEINITZ, Profesor
role: STUDY_CHAIR
affiliation: CHRU de Lille
name: Eric HACHULLA, Profesor
role: STUDY_CHAIR
References:
citation: Hamidou M, Neel A, Poupon J, Amoura Z, Ebbo M, Sibilia J, Viallard JF, Gaborit B, Volteau C, Hardouin JB, Hachulla E, Rieger F. Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic). Arthritis Res Ther. 2021 Mar 3;23(1):70. doi: 10.1186/s13075-021-02454-6.