Clinical Trials Register

Summary
EudraCT Number:	2010-023396-25
Sponsor's Protocol Code Number:	SM101-201-sle-10
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2010-023396-25

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

SMILE

A.4.1

Sponsor's protocol code number

SM101-201-sle-10

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SuppreMol GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Suppremol GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Suppremol GmbH
B.5.2	Functional name of contact point	Medical Director
B.5.3	Address:
B.5.3.1	Street Address	Am Klopferspitz 19
B.5.3.2	Town/ city	Martinsried/Munich
B.5.3.3	Post code	82152
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049089309050680
B.5.5	Fax number	00490893090506868
B.5.6	E-mail	info@suppremol.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/462
D.3 Description of the IMP
D.3.1	Product name	soluble Fc-gamma receptor IIb
D.3.2	Product code	SM101
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	SM101
D.3.9.3	Other descriptive name	soluble Fc receptor
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Systemic lupus erythematosus (SLE)

E.1.1.1

Medical condition in easily understood language

Auto-immune disease

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10042945
E.1.2	Term	Systemic lupus erythematosus
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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 equal to or greater than 40 kg and less than or equal to 100 kg
4. Diagnosis of SLE meeting at least four revised main classification criteria of the ACR
5. Clinically active patients with a Safety of Estrogen in Lupus Erythematosus National
Assessment version of the Systemic Lupus Erythematosus Disease Activity Index
(SELENA-SLEDAI) score of equal to or greater than 6 within 8 weeks preceding the first dose of investigational product. A subpopulation will fulfil the additional criterion of lupus nephritis:
• History of class III, IV, V or a combination, excluding pure class V
glomerulonephritis confirmed by renal biopsy according to the International
Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification within
36 months preceding the first dose of investigational product.

6. Patients with a current serological active status defined as an increased serum anti-dsDNA > 25% by Farr assay or above the upper limit of normal (ULN) [SELENA-SLEDAI score = 2] and/or a decrease in C3 and below lower limit of normal (LLN) [SELENA-SLEDAI score = 2]. Abnormality will be confirmed by a central laboratory from a serum sample taken within 3 weeks preceeding the first dose of investigational product
7. Patient has completed immunosuppressant SLE treatment (if any) for active
glomerulonephritis or major organ involvement with cyclophosphamide, MMF, AZA,
methotrexate, cyclosporine, etc., other than listed in inclusion criterion No. 8, within
8 weeks preceding the first dose of investigational product administration
8. Concurrent maintenance immunosuppressant SLE treatment (if any) with less than or equal to 20 mg/day prednisone (or equivalent) alone or in combination with either less than or equal to 2 mg/kg/day AZA or less than or equal to 2 g/day MMF has been stable for 4 weeks preceding the first dose of investigational product and is intended to remain stable within 4 weeks after first dose of investigational
product
9. Concurrent adjuvant maintenance SLE treatment (if any) such as antimalarials,
angiotesnin-converting enzyme (ACE) inhibitors, NSAIDs, cyclooxygenase inhibitors,
anticoagulation- and antiplatelet agents, hormone replacement therapy, etc., has been stable for 4 weeks preceding the first dose of investigational product and is intended to remain stable within 4 weeks after first dose of investigational product
10. Women of childbearing potential must have a negative serum pregnancy test within 3 weeks preceding the first dose of investigational product and a negative urine pregnancy test on study Day 1
11. Both women of childbearing potential and men must use a medically acceptable method of contraception prior to inclusion, throughout the study, and within
4 weeks after investigational product discontinuation
12. Adequate liver function expressed as:
a) Aspartate aminotransferase (AST) less than or equal to 3 times ULN and
b) Alanine aminotransferase (ALT) less than or equal to 3 times ULN and
c) Serum bilirubin less than or equal to 3 times ULN
13. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2, with a life expectancy of at least 9 months

E.4

Principal exclusion criteria

1. Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period
2. Patient is intended to receive immunosuppressive SLE treatment other than listed in inclusion criterion No. 8 within 4 weeks after first dose of investigational product
3. Patients with proteinuria > 3.5 g/day at baseline or glomerular filtration rate (GFR)
< 60 mL/min/1.73 m2
4. Patients with active SLE neurological disorders as described in Section 8 of the revised ACR SLE criteria within 12 weeks preceding the first dose of investigational product
5. Patients with a BILAG score defined as equal to or greater than 1 BILAG A score or equal to or greater than 2 BILAG B scores within 8 weeks preceding the first dose of investigational product
6. History of class VI glomerulonephritis
7. Patients with non-lupus related renal disease such as microthrombotic disease associated with antiphospholipid syndrome
8. Patients with known retroviral infection such as human immunodeficiency virus (HIV), hepatitis B or C
9. Patients with other acute infections within 4 weeks preceding the first dose of
investigational product
10. Patient received intravenous immunoglobulins (IVIGs) treatment within 12 weeks
preceding the first dose of investigational product
11. Patient received any B cell depleting therapy (e.g. Rituximab) within 48 weeks preceding the first dose of investigational product
12. Any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with all study procedures
13. Known hypersensitivity to any recombinant E. coli-derived product or investigational product excipients (Polysorbat 20, Mannitol, Sucrose)
14. Patients participating in a concurrent clinical trial or treated with another investigational product within 4 weeks or five terminal half-lives (whichever is longer) preceding the first dose of investigational product
15. History of alcohol or drug abuse within the previous 5 years
16. Any condition which in the judgment of the Investigator would place the patient at undue risk or interfere with the results of the study
17. Patients with an active malignancy
18. Patients with active, serious, life-threatening disease with a life expectancy of less than 9 months

E.5 End points

E.5.1

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Over a 24 week period

E.5.2

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)
• Percent change of urine protein
• Percent change of glomerular filtration rate (GFR)
• Change in proportion of patients with active urine sediment defined as equal to or greater than 5 white blood cell (WBC) count/high power field (HPF) or equal to or greater than 5 red blood cell (RBC) count/HPF or equal to or greater than 1 cellular
cast
• Percent change of urinary neutrophil gelatinase-associated lipocalin (uNGAL)
• Proportion of patients with a complete or partial renal SLE response according to the kidney response criteria defined by the Systemic Lupus International Collaborating
Clinics (SLICC) group
• Incidence of end-stage renal disease (ESRD) requiring dialysis or renal transplantation

Serology parameters
• Percent change of anti-double-stranded DNA-antibodies (antidsDNA),
anti-complement-component C1q-antibodies (anti- C1q), C3 and C4 concentration
• Proportion of patients with a serological SLE response (defined as: a) 25% increase of C3 level and b) 4-fold decrease in anti-dsDNA concentration from baseline)

Numerical scoring parameters
• Renal activity score according to SLICC criteria • Percent change of the Safety of Estrogen in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENASLEDAI) score
• Percent change of British Isles Lupus Assessment Group BILAG score
• Percent change of the Physician Global Assessment (PGA) score
• Proportion of patients with a clinical SLE response (defined as reduction of at least 4, 5, 6 or 7 points in the SELENASLEDAI score from baseline)
• Proportion of patients with flares defined as 1 new BILAG A score or 2 new BILAG B scores
• Time to flare defined as 1 new BILAG A score or 2 new BILAG B scores
• Proportion of patients with no worsening (< 0.3 point increase from baseline) in the PGA score

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

Other
• Number of unscheduled hospital days • Investigational product PK parameters

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

France

Germany

Italy

Poland

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero