A study to assess the safety and effectiveness of SL101 in the treatment of systemic lupus erythematosus (SLE)

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2010-023396-25-GB
• Date of registration: 11/04/2011
• Prospective Registration: Yes
• Primary sponsor: SuppreMol GmbH
• Public title: A study to assess the safety and effectiveness of SL101 in the treatment of systemic lupus erythematosus (SLE)
• 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 - SMILE
• Date of first enrolment: 22/09/2011
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023396-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Medical Director
• Affiliation: Suppremol GmbH

• Name: Medical Director
• Affiliation: Suppremol GmbH

Key inclusion & exclusion criteria

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.Patients with a body weight between = 40 kg and = 100 kg
4.At least 4 criteria of the American College of Rheumatology (ACR) revised criteria (APPENDIX 1) documented in the medical history
5.A SELENA-SLEDAI score of at least 6 within 8 weeks prior to the first IP dosing.
A subpopulation will fulfil in addition the following criteria for lupus nephritis:
a) A history of class III, IV, or a combination of these with class V glomerulonephritis, within 60 months prior to first IP dosing confirmed by a renal biopsy according to the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) [APPENDIX 2].
The patient had never a pure class V or VI glomerulonephritis
during the disease course
AND
b) Proteinuria between > 0.2 to = 3.5 g/day at SCR
6.Patients with a present serological active status defined as abnormal laboratory values from the last 2 local serum samples for the following parameters:
a) serum antibodies against double-stranded DNA (anti-dsDNA) above upper limit of normal (ULN)
OR/AND
b) complement component 3 (C3) below lower limit of normal (LLN)
Abnormality will be confirmed by a central laboratory during screening.
7.Patients with immunosuppressant SLE treatment (if any) other than listed under 8. have completed their SLE therapy prior to first IP dosing as follows:
a) B-cell depleting agents (e.g. rituximab, epratuzumab, etc.) for = 48 weeks
b) B-cell modifying agents (e.g. belimumab, atacicept, etc.) for = 24 weeks
c) Intravenous immunoglobulins (IVIGs) for = 12 weeks
d) All other immunosuppressive SLE treatment (e.g. metho-trexate, cyclophosphamide, cyclosporine, tacrolimus, etc.) for = 8 weeks
8.Patients with a stable maintenance immunosuppressant SLE treatment (if any) within 4 weeks prior to first IP dosing consisting of:
= 20 mg/day prednisone (or equivalent)
alone or in combination with either
a) = 2 mg/kg/day azathioprine (AZA)
OR
b) = 2 g/day mycophenolate mofetil (MMF) [or equivalent]

9.The maintenance immunosuppressant SLE treatment is intended to remain stable during the clinical trial but at least within 4 weeks after the first IP dosing

10.Patients with a stable adjuvant maintenance SLE treatment (if any) such as antimalarias, angotensin-converting enzyme (ACE) inhibitors, non-steroid anti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors, anticoagulation- and antiplatelet agents, hormone replacement therapy, etc. within 4 weeks prior to first IP dosing. The adjuvant maintenance SLE treatment is intended to remain stable during the clinical trial but at least within 4 weeks after first IP dosing
11.Women of childbearing potential must have a negative serum pregnancy test within 3 weeks preceding the first dose of IP and a negative urine pregnancy test on study day 1
12.Both women of childbearing potential and men must use a medically acceptable method of contraception (APPENDIX 7) prior to inclusion, throughout the study, and within 12 weeks after IP discontinuation
13.Eastern Cooperative Oncology Group (ECOG) performance status = 2, with a life expectancy of at least 9 months (APPENDIX 8)

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 47
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects
Exclusion criteria:
1.Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period
2.Patients with active SLE neurological disorder documented according to the ACR SLE criteria as listed in APPENDIX 1 within 12 weeks prior to first IP dosing
3.Patients with non-lupus related renal diseases or microthrombotic disease associated with antiphospolipid syndrome
4.Patients with known active retroviral infection such as as human immunodeficiency virus (HIV), hepatitis B or C
5.Patients with other acute infections (except minor infections such as common cold) within 4 weeks prior to first IP dosing
6.Patients with a glomerular filtration rate (GFR) of < 45 mL/min/1.73 m2
7.Patients with inadequate liver function expressed as at least one of the following:
a) Aspartate aminotransferase (AST) > 3 times ULN OR
b) Alanine aminotransferase (ALT) > 3 times ULN OR
c) Serum bilirubin > 3 times ULN
8.Any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with all study procedures
9.Known hypersensitivity to any recombinant E. coli-derived product or IP excipients (Polysorbat 20, Mannitol, Sucrose)
10.Patients participating in a concurrent clinical trial or treated with another IP within 4 weeks or five terminal half-lives (whichever is longer) prior to first IP dosing
11.History of alcohol or drug abuse within the previous 5 years
12.Any condition which in the judgment of the Investigator would place the patient at undue risk or interfere with the results of the study
13.Patients with an active malignancy
14.Patients with active, serious, life-threatening diseases



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic lupus erythematosus (SLE)
MedDRA version: 14.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: soluble Fc-gamma receptor IIb
Product Code: SM101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: .
CAS Number: .
Current Sponsor code: SM101
Other descriptive name: soluble Fc receptor
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Incidence of adverse events (AEs) during the study period according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

Main Objective: Evaluate the safety of 6.0 mg/kg and 12 mg/kg SM101 per week in SLE patients with or without a history of lupus nephritis.

Secondary Objective: Evaluate the efficacy and pharmacokinetics (PK) of 6.0 mg/kg and 12 mg/kg SM101 per week in SLE patients with or without a history of lupus nephritis.

Timepoint(s) of evaluation of this end point: Over a 24 week period

Secondary Outcome(s)

Secondary end point(s): Efficacy
Kidney parameters
•Change in proportion of patients with proteinuria (urine protein > 0.2, > 0.5, > 1.0 and > 2.0 g/day) from screening (SCR) to end of week 4, 12 and 24
•Percent change of urine protein from SCR to end of week 4, 12 and 24
•Percent change of glomerular filtration rate (GFR) from SCR to end of week 4, 12 and 24
•Change in proportion of patients with active urine sediment defined as = 5 white blood cell (WBC) count/high power field (HPF) or = 5 red blood cell (RBC) count/HPF or = 1 cellular cast from SCR to end of week 4, 12 and 24
•Percent change of urinary neutrophil gelatinase-associated lipocalin (uNGAL) from SCR to end of week 4, 12 and 24
•Proportion of patients with a complete or partial renal SLE response according to the Renal Response Index (RRI) from SCR to end of week 4, 12 and 24
•Incidence of end-stage renal disease (ESRD) requiring dialysis or renal transplantation from SCR to end of week 24

Serology parameters
•Percent change of anti-double-stranded DNA-antibodies (anti-dsDNA), anti-complement-component C1q-antibodies (anti-C1q), C3 and C4 concentration from SCR to end of week 4, 12 and 24
•Proportion of patients with a serological SLE response, defined as: a) = 25% increase of C3 level and
b) = 25% decrease in anti-dsDNA concentration from SCR at end of week 4, 12 and 24

Numerical scoring parameters
•Renal activity score according to RRI from SCR to end of week 4, 12 and 24
•Absolute change of the Safety of Estrogen in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score from SCR to end of week 4, 12 and 24 (refer to APPENDIX 3 for the SLEDAI form)
•Absolute change of British Isles Lupus Assessment Group (BILAG) score from SCR to end of week 4, 12 and 24
•Absolute change of the Physician Global Assessment (PGA) score from SCR to end of week 4, 12 and 24
•Proportion of patients with a clinical SLE response (defined as reduction of at least 4, 5, 6 or 7 points in the SELENA-SLEDAI score from SCR) at end of week 4, 12 and 24
•Proportion of patients with flared defined as = 1 new BILAG A score or = 2 new BILAG B score from SCR to end of week 24
•Time to flare defined as = 1 new BILAG A score or = 2 new BILAG B scores from SCR to end of week 24
•Proportion of patients with no worsening (< 0.3 point increase from SCR) in the PGA score to end of week 24

Treatment parameters
•Proportion of patients requiring rescue medication, defined as increase in concomitant immunosuppression or new immunosuppressant therapy including corticosteroids from day 1 to end of week 24
•Total number of rescue medication intake from day 1 to end of week 24
•Cumulative dose of overall immunosuppressive SLE treatment including corticosteroids from day 1 to end of week 24
•Proportion of patients with dose reduction of overall immunosuppressive SLE treatment including corticosteroids from day 1 to end of week 24

Other
•Number of unscheduled hospital days from day 1 to end of week 24
•IP PK parameters at end of week 1 and 4

Timepoint(s) of evaluation of this end point: From baseline to end of week 4, 12 and 24 except;
Incidence of end-stage renal disease (ESRD) requiring dialysis or renal transplantation from baseline to end of week 24
Proportion of patients with flares defined as 1 new BILAG A score or 2 new BILAG B scores from baseline to end of week 24
Time to flare defined as 1 new BILAG A score or 2 new BILAG B scores from baseline to end of week 24
Proportion of patients with no worsening (< 0.3 point increase from baseline) in the PGA score to end of week 24
Treatment parameters from baseline to end of week 24
Number of unscheduled hospital days from baseline to end of week 24
Investigational product PK parameters at end of week 1 and 4

Secondary ID(s)

SM101-201-sle-10

Source(s) of Monetary Support

Suppremol GmbH

Ethics review

Status: Approved
Approval date:
Contact: