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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Nantes University Hospital
Sponsor:
Collaborator:
Medsenic Company
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT01738360
First received: November 28, 2012
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

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.

Condition Intervention Phase
Systemic Lupus
Drug: Arsenic trioxide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE)

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Cardiac adverse events whatever grade and any adverse event of grade 3 or 4 [ Time Frame: 30 days after the last infusion ] [ Designated as safety issue: Yes ]

    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.


Secondary Outcome Measures:
  • Composite response of SLE [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    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.

  • Anti-nuclear antibodies (ANA). [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    The modification of anti-nuclear antibodies (ANA).

  • Anti-native DNA [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    The modification of anti-native DNA.

  • C3 complement [ Time Frame: 30 monhs ] [ Designated as safety issue: No ]
    The modification of C3 complement.

  • C4 complement [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    The modification of C4 complement.

  • Sedimentation rate [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Analysis of Sedimentation rate.

  • Serum creatinine [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Analysis of serum creatinine.

  • Proteinuria/creatinuria ratio [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Analysis of proteinuria/creatinuria ratio.

  • Serum protein electrophoresis [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Analysis of serum protein electrophoresis.

  • Quantitation of immunoglobulins [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Analysis of quantitation of immunoglobulins.

  • Quality of life [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assessment of quality of life wih questionnaires SF36 and LupusQol.

  • Steroids [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Reduction of the dose of steroids throughout the study.

  • Immunosuppressive treatments [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Cessation of immunosuppressive treatments.

  • Response time [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Response time in case of positive response.

  • Time to relapse [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Time to relapse in case of positive response.

  • Blood test of arsenic [ Time Frame: D1, D2, D3, D4, D8, D11, D15, D18, D22 and D25 (before and after each infusion) ] [ Designated as safety issue: No ]
    Pharmacokinetic study of arsenic plasma with analysis of potential correlations blood rates/ toxicity and response.


Estimated Enrollment: 13
Study Start Date: July 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738360

Contacts
Contact: Mohamed HAMIDOU, Profesor 02 40 08 31 46 mohamed.hamidou@chu-nantes.fr

Locations
France
Nantes University Hospital Recruiting
Nantes, France, 44093
Contact: Mohamed HAMIDOU, Profesor    02 40 08 31 46    mohamed.hamidou@chu-nantes.fr   
Principal Investigator: Mohamed HAMIDOU, Profesor         
Sponsors and Collaborators
Nantes University Hospital
Medsenic Company
Investigators
Principal Investigator: Mohamed HAMIDOU, Profesor CHU de Nantes
Study Chair: Zahir AMOURA, Profesor AP-HP - La Pitié-Salpétrière
Study Chair: Jean SIBILIA, Profesor CHRU de Strasbourg
Study Chair: Jean-François VIALLARD, Profesor University Hospital, Bordeaux
Study Chair: Nicolas SCHLEINITZ, Profesor CHU de Marseille
Study Chair: Eric HACHULLA, Profesor CHRU de Lille
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01738360     History of Changes
Other Study ID Numbers: RC12_0021, 2012-002259-40
Study First Received: November 28, 2012
Last Updated: May 23, 2014
Health Authority: France : ANSM - Agence Nationale de Sécurité du Médicament et des Produits de Santé

Keywords provided by Nantes University Hospital:
Arsenic trioxide
Systemic Lupus
clinically
biologically active

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Arsenic trioxide
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014