Clinical Trials Register

Summary
EudraCT Number:	2015-002345-64
Sponsor's Protocol Code Number:	181501
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-09-08
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2015-002345-64

A.3

Full title of the trial

A Phase 2 Study to Assess the Efficacy and Safety of Intravenous Infusion with Human Soluble Recombinant Fc-gamma Receptor IIB (SM101/BAX 1810) in Subjects with Immunoglobulin A Nephropathy (IgAN)

Klinické hodnocení fáze 2 posuzující účinnost a bezpečnost nitrožilní infuze lidského rozpustného rekombinantního Fc-gama receptoru IIB (SM101/BAX 1810) u pacientů s nefropatií s ukládáním depozit z imunoglobulinu A (IgAN)

A.3.1

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

Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy

A.3.2

Name or abbreviated title of the trial where available

Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy

Účinnost a bezpečnost SM101 v léčbě IgA nefropatie

A.4.1

Sponsor's protocol code number

181501

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	Baxalta Innovations GmbH
B.1.3.4	Country	Austria
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	Baxalta Innovations GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Baxalta Innovation GmbH
B.5.2	Functional name of contact point	Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	Industriestrasse 67
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	A-1221
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43 120 1002472930

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
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.3.8	INN - Proposed INN	Not available
D.3.9.2	Current sponsor code	SM101
D.3.9.3	Other descriptive name	human soluble recombinant Fc-gamma receptor IIB
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

IgA Nephropathy

E.1.1.1

Medical condition in easily understood language

an autoimmune disease resulting in inflammation of the kidney, which can lead to destruction of the kidneys over time in about a third of the patients

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10021263
E.1.2	Term	IgA nephropathy
E.1.2	System Organ Class	10038359 - Renal and urinary 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

To assess the efficacy of a single treatment cycle of SM101 on the mean percent change in proteinuria from Baseline to Week 24 in subjects with IgAN

E.2.2

Secondary objectives of the trial

1. To assess the safety and tolerability of SM101 in subjects with IgAN
2. To compare the relative efficacy and safety of 12 mg/kg and 24 mg/kg doses of SM101 in the treatment of IgAN
3. To assess the effect of SM101 on renal function, as determined by estimated glomerular filtration rate (eGFR)
4. To compare the effect of treatment with SM101 on the level of IgAN-specific biomarkers
5. To assess the pharmacokinetics (PK) of SM101 in subjects with IgAN

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is 18 years of age or older at the time of Screening.
2. Subject may be of either gender and of any race or ethnicity.
3. Subject must have a biopsy-proven diagnosis of IgAN (obtained within 8 years
prior to Screening).
4. Subject’s blood pressure is ≤130/80 mmHg at Screening.
5. Subject is on maximally tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) for at least 3 month prior to Baseline visit.
6. Subject must present at Screening with current proteinuria levels between 1 g/24 h and 3.5 g/24 h.
7. Subject must present at Screening with eGFR [CKD-EPI] >40 mL/min/1.73m2.
8. If a female of childbearing potential, subject must have a negative pregnancy test at Screening, is not currently breastfeeding, and agrees to employ adequate birth control measures for the duration of the study. Male subjects with female partners of childbearing potential must agree to use adequate birth control measures for the duration of the study.
9. Subject is willing and able to comply with the requirements of this protocol and
agrees to sign an informed consent form prior to any study-related activities.

E.4

Principal exclusion criteria

1. Subject has a history or current evidence of renal disease other than IgAN
2. Subjects with evidence of rapidly progressive disease (defined as a decline in
eGFR of ≥5 mL/min/1.73m2 in the preceding 6 months prior to Baseline)
3. Subject has IgAN with histologic evidence of advanced tubular atrophy and
interstitial fibrosis (eg, Oxford T2)
4. History or current evidence of other autoimmune disease (eg, SLE, inflammatory
bowel disease, rheumatoid arthritis)
5. History or current evidence of any chronic or uncontrolled medical condition (eg,
diabetes, severe hepatic or cardiovascular disease, alcohol or drug addiction)
which could, in the opinion of the Investigator, affect the subject’s safety and
ability to adhere to this protocol, or otherwise confound the results of the study
6. History or current evidence of a severe acute (ie, within 4 weeks prior to
Baseline) or chronic infection (eg, HIV, hepatitis B or C, tuberculosis, systemic
fungal infection [active or latent])
7. Use of systemic corticosteroids within 3 months prior to Baseline, or anticipated
use during the treatment period (Week 1 through Week 4). Note: Corticosteroids
administered by inhalation or intranasally, or limited topical use of low-potency
topical corticosteroids (ie, Class 6 and 7) are allowed throughout the study.
8. Known hypersensitivity or allergic reaction to any E. coli-derived recombinant
product, or to the IP or any of its excipients
9. Treatment with any immunomodulatory/immunosuppressive compound or
monoclonal antibody for any indication within 6 months (unless otherwise
stated) prior to Screening (eg, B cell-depleting agents [eg, rituximab,
epratuzumab] for ≥48 weeks; B-cell modifying agents [eg, belimumab, atacicept]
for ≥24 weeks; IV immunoglobulins for ≥12 weeks and all other
immunosuppressive treatments [eg, methotrexate, cyclophosphamide,
cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine] for ≥12 weeks)
10. Clinically significant laboratory abnormalities prior to Baseline (eg, absolute
neutrophil count <1000 cells/μL; platelet count <100,000/μL; hemoglobin ≤10
g/dL; aspartate aminotransferase [AST], and alanine aminotransferase [ALT] ≥3
times the upper limit of normal)
11. History of any malignancy within past 5 years prior to Screening (except for
basal and squamous cell carcinomas of the skin, in situ cervical cancer, and
stable prostate cancer that does not require treatment)
12. History of tonsillectomy within 2 months prior to Screening
13. Subject has participated in another clinical study involving an IP or
investigational device within 30 days prior to Screening or is scheduled to
participate in another clinical study involving an IP or investigational device
during the course of this study
14. Subject is a family member or employee of the Investigator
15. A female subject who is pregnant or nursing at the time of Screening

E.5 End points

E.5.1

Primary end point(s)

To assess the efficacy of a single treatment cycle of SM101 on the mean percent change in proteinuria from Baseline to Week 24 in subjects with IgAN
1. Pooled high-dose SM101 and low-dose SM101 versus placebo
2. High-dose SM101 versus placebo
3. Low- dose SM101 versus placebo

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

Secondary end point(s)

1. Pooled high-dose SM101 and low-dose SM101 versus placebo (testing via 2x2
table by pooling high- and low-dose SM101 into single column, using placebo
as the second column).
2. High-dose SM101 versus placebo (testing via 2x2 table, using only SM101
high-dose and placebo)
3. Low- dose SM101 versus placebo (testing via 2x2 table, using only SM101
low-dose and placebo)

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 24

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

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

Belgium

Canada

Czech Republic

Denmark

Germany

Hong Kong

Sweden

United Kingdom

United States

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

LVLS

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects who complete the 24-week randomized, double-blind study, and who meet additional eligibility criteria, will be allowed to participate in an open-label continuation study to assess the long-term effect of treatment with SM101 on proteinuria and renal function (assessed by changes in eGFR over time). Additional study drug administration will be considered based on progression of disease and on availability of the investigational product (IP).

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-10-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-12-10

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials