Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE) (Protocol LUPSENIC)

Systemic Lupus Clinical Trial

— LUPSENIC  

Official title:

Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01738360
• Other study ID #: RC12_0021
• Secondary ID: 2012-002259-40
• Status: Terminated
• Phase: Phase 2
• First received: November 28, 2012
• Last updated: January 5, 2016
• Start date: July 2013
• Est. completion date: October 2015

Study information

• Verified date: January 2016
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France : ANSM - Agence Nationale de Sécurité du Médicament et des Produits de Santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus

Intervention

Drug:
• Arsenic trioxide
The study duration was 30 months (24 months recruitment + 6 months follow-up).Thirteen patients will be successively included in this study at 6 different dose levels of arsenic trioxide (0.075, 0.10, 015, 0.20, 0.25 and 0.30 mg / kg / day). The treatment should be administered by IV infusion over 2 hours of D1 to D4 (conventional hospitalization) and at D8, D11, D15, D18, D22 and D25. The protocol starts at the dose of 0.10 mg / kg / day. The stage at the dose of 0.075mg/kg/day is planned in case of toxicity with the first stage at the dose of 0.10mg/kg/day. The course of study is as follows : Pre-inclusion between D-35 and D-15 Ten injections during the first month distributed as follows : conventional hospitalization from D1 to D4 (one injection per day) and daily hospitalization day for injections at D8, D11, D15, D18, D22 and D25. A telephone contact between D32 and D34 A consultation at D40 then monthly consultation at D60, D90, D120, D150 and D180

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	CHRU de Lille	Lille
France	CHU de Marseille	Marseille
France	Nantes University Hospital	Nantes
France	AP-HP - la Pitié-Salpétrière	Paris
France	CHRU de Strasbourg	Strasbourg

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	Medsenic Company

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac adverse events whatever grade and any adverse event of grade 3 or 4	The definition of toxicity will be based on "Common Terminology Criteria for Adverse Events, version 4" of the U.S. Department of Health and Human Services, National Institutes of Health / National Cancer Institute.; The investigators will consider the occurrence of a significant toxicity if at least one of the following events is observed : Any symptomatic toxicity (and / or abnormality) cardiac and / or QTc prolongation > 480 msec.,; Apart from cardiac toxicity, toxicity of any grade 3 or 4 and irreversible toxicity (within 30 days) of any grade 1 or 2.	30 days after the last infusion	Yes
Secondary	Composite response of SLE	Combined clinical response using the composite response of SLE or SRI (SLE Responder Index) (SLEDAI + BILAG (British Isles Lupus Assessment Group) + PGA) : a positive response is defined by a reduction of SELENA SLEDAI of at least 4 points, no worsening ( > 0,3 point) of the physician's global assessment (PGA), no new score "A" and no more than one new score "B" about BILAG. This composite index is now the benchmark tool for evaluating therapeutic protocols in SLE.	30 months	No
Secondary	Anti-nuclear antibodies (ANA).	The modification of anti-nuclear antibodies (ANA).	30 months	No
Secondary	Anti-native DNA	The modification of anti-native DNA.	30 months	No
Secondary	C3 complement	The modification of C3 complement.	30 monhs	No
Secondary	C4 complement	The modification of C4 complement.	30 months	No
Secondary	Sedimentation rate	Analysis of Sedimentation rate.	30 months	No
Secondary	Serum creatinine	Analysis of serum creatinine.	30 months	No
Secondary	Proteinuria/creatinuria ratio	Analysis of proteinuria/creatinuria ratio.	30 months	No
Secondary	Serum protein electrophoresis	Analysis of serum protein electrophoresis.	30 months	No
Secondary	Quantitation of immunoglobulins	Analysis of quantitation of immunoglobulins.	30 months	No
Secondary	Quality of life	Assessment of quality of life wih questionnaires SF36 and LupusQol.	30 months	No
Secondary	Steroids	Reduction of the dose of steroids throughout the study.	30 months	No
Secondary	Immunosuppressive treatments	Cessation of immunosuppressive treatments.	30 months	No
Secondary	Response time	Response time in case of positive response.	30 months	No
Secondary	Time to relapse	Time to relapse in case of positive response.	30 months	No
Secondary	Blood test of arsenic	Pharmacokinetic study of arsenic plasma with analysis of potential correlations blood rates/ toxicity and response.	D1, D2, D3, D4, D8, D11, D15, D18, D22 and D25 (before and after each infusion)	No