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

NCT ID: NCT01738360

Last Updated: 2016-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-10-31

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.

Conditions

Systemic Lupus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arsenic trioxide

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).

Group Type: EXPERIMENTAL

Arsenic trioxide

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medsenic Company

UNKNOWN

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamed HAMIDOU, Profesor

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Zahir AMOURA, Profesor

Role: STUDY_CHAIR

AP-HP - La Pitié-Salpétrière

Jean SIBILIA, Profesor

Role: STUDY_CHAIR

CHRU de Strasbourg

Jean-François VIALLARD, Profesor

Role: STUDY_CHAIR

University Hospital, Bordeaux

Nicolas SCHLEINITZ, Profesor

Role: STUDY_CHAIR

CHU de Marseille

Eric HACHULLA, Profesor

Role: STUDY_CHAIR

CHRU de Lille

Locations

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, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 33658052 (View on PubMed)

Other Identifiers

2012-002259-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC12_0021

Identifier Type: -

Identifier Source: org_study_id