Trial document




drksid header

  DRKS00003248

Trial Description

start of 1:1-Block title

Title

Phase IIa, 2:2:1 randomised, double-blind, placebo-controlled, parallel group, multi-centre clinical trial to investigate the safety, efficacy and pharmacokinetics of recombinant human soluble Fc-gamma receptor IIb (SM101) for intravenous application in the treatment of systemic lupus erythematosus (SLE) patients with or without a history of lupus nephritis

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

SMILE - SM101 in Lupus Erythematosus

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

http://www.suppremol.com/index.php?id=clinicaltrials

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

This study investigates a new treatment for preventing and/ or ameliorating systemic lupus erythematosus (SLE) in patients with or without a history of lupus nephritis. The main purpose of this study is to find a dose of the study drug that is safe and effective in the treatment of SLE.
Previous investigations in SLE animal studies suggest that the investigational drug SM101 competes with the immune complex binding and thus has the potential to prevent organ damage caused by the activated immune system.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

In autoimmune diseases, such as SLE or ITP, the patient’s immune system has lost the ability to discriminate between body-own (“self”) and foreign proteins. In consequence, antibodies are generated that recognise “self”-proteins and form immune complexes which continuously activate the immune system because the “self”- protein is permanently produced. This chronic condition can persist for years leading in the end to severe organ damage and to the death of the patient. In SLE, human auto-immune antibodies form complexes with double-stranded DNA (dsDNA), nucleosomes, complement component 1q (C1q) and other self-structures, which are subsequently recognised by cell-bound Fc-receptors that mediate phagocytosis of these immune complexes leading to inflammation, organ damage and additional immunological activation.
The recombinant human SM101 competes for the interaction with immune complexes, thereby preventing the binding of these immune complexes to the cell. In in-vitro and in-vivo experiments it could be shown that administration of SM101 significantly inhibits antigen presenting cells and the secretion of interleukin-6 (IL-6) and tumour necrosis factor (TNF), which resulted in an inhibition of B-cells and reduced levels of pathogenic antibodies. As a result, the feedback loop of autoantibody production, immune complex formation and re-stimulation of immune cells is inhibited and, in consequence, inflammation, organ damage and additional immunological activation are prevented.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003248
  •   2011/09/02
  •   2011/08/25
  •   no
  •   Approved
  •   ML 6066, Institutional Review Board - ZMA/OCMW Antwerpen, Lindendred 1, 2020 Antwerpen, Belgium
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2010-023396-25 
  •   ISRCTN84672048   (Current Controlled Trials Database)
  •   4037367 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   M32 -  Systemic lupus erythematosus
  •   [---]* -  [---]*
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Placebo/week for 4 weeks given as 1 hour intravenous infusion
  •   6 mg/kg/week SM101 for 4 weeks given as 1 hour intravenous infusion
  •   12 mg/kg/week SM101 for 4 weeks given as 1 hour intravenous infusion
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   [---]*
  •   Placebo
  •   Treatment
  •   Parallel
  •   IIa
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Incidence of adverse events during the study period according to common terminology criteria for adverse events

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

Parameters to be recorded during screening, treatment and follow-up:
Overall and renal disease score assessments, proteinuria, urine sediment, glomerular filtration rate, biological markers, anti-dsDNA, anti-C1q, C3, C4, uNGAL, use of rescue medication, vital signs, body temperature, ECG, safety laboratory assessments, anti-drug antibody, AE recording

Parameters to be recorded during screening and follow-up:
body weight

Parameters to be recorded during screening:
physical examination

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Australia
  •   Belgium
  •   Czech Republic
  •   France
  •   Germany
  •   Italy
  •   Netherlands
  •   Poland
  •   Spain
  •   United Kingdom
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • [---]*
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Planned
  •   2011/09/30
  •   50
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. Patient has provided written informed consent prior to any study-related procedure

2. Male or female adult patients aged 18 years or older

3. Diagnosis of SLE meeting at least four revised main classification criteria of the ACR with or without a history of glomerulonephritis

4. Clinically active patients with a SELENA-SLEDAI score of ≥ 6

5. Patients with a current serological active status (anti-dsDNA or C3)

6. Concurrent maintenance immunosuppressant SLE treatment (if any) with prednisone alone or in combination with either azathioprine or mycophenolate mofetil

7. Adequate liver function

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Patient is intended to receive immunosuppressive SLE treatment other than listed in the inclusion criteria

2. Patients with proteinuria > 3.5 g/day at baseline or glomerular filtration rate (GFR) < 60 mL/min/1.73 m2

3. Patients with active SLE neurological disorders

4. Patients with an acute BILAG score defined as ≥ 1 BILAG A score or ≥ 2 BILAG B scores

5. History of class VI glomerulonephritis

6. Patients with non-lupus related renal disease such as microthrombotic disease associated with antiphospholipid syndrome

7. Patients with other acute infections

8. Patient received any B cell depleting therapy

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • SuppreMol GmbH
    • Mr.  Tillmanns 
    • Am Klopferspitz 19
    • 82152  Martinsried/Munich
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • SuppreMol GmbH
    • Mr.  Sascha  Tillmanns 
    • Am Klopferspitz 19
    • 82152  Martinsried/Munich
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • SuppreMol GmbH
    • Mr.  Sascha  Tillmanns 
    • Am Klopferspitz 19
    • 82152  Martinsried/Munich
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • SuppreMol GmbH
    • Mr.  Tillmanns 
    • Am Klopferspitz 19
    • 82152  Martinsried/Munich
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting planned
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.