Condition category
Musculoskeletal Diseases
Date applied
30/06/2011
Date assigned
25/08/2011
Last edited
08/07/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
In autoimmune diseases such as systemic lupus erythematosus (SLE), the immune system has lost the ability to discriminate between body-own ('self') and foreign proteins. In consequence, antibodies are generated to attack 'self'-proteins and form immune complexes which continuously activate the immune system through binding to specific immune cells in the body. As a result, the activated immune system can lead to severe organ damage, including the kidney. This study investigates a new treatment for preventing and/ or ameliorating SLE in patients with or without a history of lupus nephritis ((prolonged inflammation of kidneys). Previous investigations in SLE animal studies suggest that the drug SM101 competes with the immune complex binding and has the potential to prevent organ damage caused by the activated immune system. The aim of the SMILE clinical trial in SLE is to investigate the safety and efficacy of SM101 in the treatment of SLE patients with or without a history of lupus nephritis and a SELENA-SLEDAI score of ≥ 6.

Who can participate?
SLE patients with or without a history of lupus nephritis and a SELENA-SLEDAI score of ≥ 6.

What does the study involve?
The study includes 10 visits for non-pharmacokinetic (PK) patients and 13 visits for PK patients. There is a 3 weeks screening period, a 4 weeks treatment and a 5 months follow-up period. SLE patients with or without a history of lupus nephritis, a SELENA-SLEDAI score of ≥ 6, serological active (abnormal dsDNA or C3 titres) with stable immunosuppressive therapy may be eligible for the study.

What are the possible benefits and risks of participating?
Previous studies suggest that SM101 appears to be generally well tolerated and safe. However some patients may experience some adverse reactions which have not been reported so far. The side effects may be a minor inconvenience or could be severe. Patients will be watched closely for any side effects, and the drug will be stopped if serious side effects develop.

Where is the study run from?
Thirty clinical trial sites for the SMILE study are located in Australia, Belgium, Czech Republic, France, Germany, Italy, Netherlands, Poland, Spain and UK.

When is the study starting and how long is it expected to run for?
The first enrolment of patients is planned for August 2011 with a recruitment period of 14 months until October 2012.

Who is funding the study?
SuppreMol GmbH (Germany)

Who is the main contact?
Sascha Tillmanns, Medical Director, SuppreMol GmbH
tillmanns@suppremol.com

Trial website

Contact information

Type

Scientific

Primary contact

Mr Sascha Tillmanns

ORCID ID

Contact details

SuppreMol GmbH
Am Klopferspitz 19
Martinsried/Munich
82152
Germany
-
tillmanns@suppremol.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SM101-201-sle-10

Study information

Scientific 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

Acronym

SMILE

Study hypothesis

The human soluble Fcγ receptor SM101 competes with the binding of systemic lupus erythematosus (SLE)-specific immune complexes to effector cells and therefore interrupts the immunological cascade leading to inflammation and organ damage.

Ethics approval

Approval pending as of 30/06/2011

Study design

Phase IIa 2:2:1 randomised double-blind placebo-controlled parallel group multi-centre proof-of-concept clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Systemic lupus erythematosus patients with or without a history of lupus nephritis

Intervention

Three treatment arms, two interventions groups and a placebo in parallel fashion:
1. Intervention group 1: 6 mg/kg/week SM101 for 4 weeks
2. Intervention group 2: 12 mg/kg/week SM101 for 4 weeks
3. Placebo

Intervention type

Drug

Phase

Phase II

Drug names

SM101

Primary outcome measures

Incidence of adverse events (AEs) during the study period according to Common Terminology Criteria for Adverse Events (CTCAE)

Secondary outcome measures

1. Physical examination (screening)
2. Vital signs (screening, treatment, follow-up)
3. Body temperature (screening, treatment, follow-up)
4. Body weight (screening, treatment)
5. Electrocardiogram (ECG) (screening, treatment, follow-up)
6. Safety laboratory assessments (screening, treatment, follow-up)
7. Anti-drug antibody (ADA) (treatment, follow-up)
8. AE recording (continuously)
9. Overall and renal disease score assessments, proteinuria, urine sediment, glomerular filtration rate (GFR), biological markers, anti-double-stranded DNA (dsDNA), anti-C1q, C3, C4, urinary neutrophil gelatinase-associated lipocalin (uNGAL) (continuously)
10. Use of rescue medication (all during screening, treatment, follow-up)

Overall trial start date

01/08/2011

Overall trial end date

01/07/2013

Reason abandoned

Eligibility

Participant 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 American College of Rheumatology (ACR) with or without a history of glomerulonephritis
4. Clinically active patients with a SLE Disease Activity Index (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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

50 patients

Participant 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 British Isles Lupus Assessment Group (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

Recruitment start date

01/08/2011

Recruitment end date

01/10/2012

Locations

Countries of recruitment

Australia, Belgium, Czech Republic, France, Germany, Italy, Poland, Spain, United Kingdom

Trial participating centre

SuppreMol GmbH
Martinsried/Munich
82152
Germany

Sponsor information

Organisation

SuppreMol GmbH (Germany)

Sponsor details

Am Klopferspitz 19
Martinsried/München
82152
Germany
-
tillmanns@suppremol.com

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

SuppreMol GmbH (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes