Clinical Trials Register

Summary
EudraCT Number:	2011-000263-27
Sponsor's Protocol Code Number:	IgPro10_4001
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-25
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

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A. Protocol Information

A.1

Member State Concerned

Bulgarian Drug Agency

A.2

EudraCT number

2011-000263-27

A.3

Full title of the trial

An open-label, prospective, multicenter study to investigate the specificity of in vivo antibody binding to red blood cells in subjects with chronic immune thrombocytopenic purpura (ITP) treated with IgPro10 (Privigen®) who have shown signs of hemolysis.

A.3.1

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

An non-blinded, mulicenter study to investigate the mechanisms which are involved in the interaction of red blood cells with the study drug IgPro10 in patients with chronic immune thrombocytopenic purpura (ITP) who have shown signs of hemolysis (a breakdown or destruction of red blood cells).

A.3.2

Name or abbreviated title of the trial where available

Privigen® in ITP

A.4.1

Sponsor's protocol code number

IgPro10_4001

A.5.4

Other Identifiers

Name:

Number:

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	CSL Behring 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	CSL Behring 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	CSL Behring GmbH
B.5.2	Functional name of contact point	(Babette von Hagen) Senior CRA
B.5.3	Address:
B.5.3.1	Street Address	Emil-von-Behring-Straße 76
B.5.3.2	Town/ city	Marburg
B.5.3.3	Post code	35041
B.5.3.4	Country	Germany
B.5.4	Telephone number	496421396763
B.5.5	Fax number	496421392870
B.5.6	E-mail	babette.vonhagen@cslbehring.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	Yes
D.2.1.1.1	Trade name	Privigen®
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.1	Product name	Privigen®
D.3.4	Pharmaceutical form	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	Human Normal Immunoglobulin G (IgG > 98% purity)
D.3.9.3	Other descriptive name	HUMAN NORMAL IMMUNOGLOBULIN
D.3.9.4	EV Substance Code	SUB14196MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	Yes
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic immune thrombocytopenic purpura (ITP)

E.1.1.1

Medical condition in easily understood language

The condition of having a low platelet count (thrombocytopenia) of no known cause (idiopathic)

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10021245
E.1.2	Term	Idiopathic thrombocytopenic purpura
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to investigate the specificity of in vivo antibody binding to red blood cells
(RBCs) in 10 subjects with chronic ITP who have shown signs of hemolysis and who experience clinically
significant intravascular hemolytic reactions following treatment with IgPro10. The study will explore potential
mechanisms of hemolysis by analysis of the specificity of the antibodies possibly involved.

E.2.2

Secondary objectives of the trial

The secondary objectives are to assess other safety and efficacy parameters, including the rates of presumptive
hemolytic events and clinically significant intravascular hemolytic reactions.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Diagnosis of chronic ITP defined by:
- Failure to find other causes of thrombocytopenia,
- Platelet count of ≤ 150 x 109/L over 6 months or response to a previous treatment with subsequent decrease in platelet count even if duration of chronic ITP is less than 6 months;
• Age of 18 to 65 years;
• Platelet count of ≤ 30 x 109/L at screening;
• Written informed consent for study participation obtained before undergoing any study specific procedures.

E.4

Principal exclusion criteria

• Planned splenectomy throughout the study period;
• Treatment with IVIG or anti-D immunoglobulin within 3 weeks prior to screening;
• Drugs that have any pharmacological effect on the blood clotting system within 3 weeks prior to screening
(i.e., clotting factors, heparin, coumarin derivates, acetylsalicylic acid in high dose, and thrombopoietin receptor agonists [e.g., eltrombopag and romiplostim]);
• Known allergic or other severe reactions to blood products including intolerability to previous IVIG (i.e. aseptic meningitis, recurrent severe headache, hypersensitivity, intravascular hemolysis);
• Known hyperprolinemia;
• IgA levels below the detection limit
• Abnormal results in the following laboratory parameters at screening:
- Hemoglobin < 11 g/dL,
- Positive DAT,
- Indirect bilirubin > the upper limit of the normal range (ULN),
- Serum free haptoglobin < 0.2 g/L,
- LDH > ULN,
- Alanine aminotransferase (ALAT) > 2.5 x ULN,
- Aspartate aminotransferase (ASAT) > 2.5 x ULN,
- Creatinine > 1.5 x ULN,
- Reticulocyte count > 1.5 x ULN,
- Iron < 50% of LLN
- Ferritin < 50 of LLN
- Vitamin B12 < 50% of LLN;
• Pregnancy, lactation, or planned pregnancy;
• RBC transfusion or erythropoietin treatment within the last 14 days;
• One of the following concomitant diseases:
- Clinically active systemic lupus erythematosus,
- Known or suspected HIV infection,
- Acute hepatitis,
- Clinically active chronic hepatitis,
- Lymphoproliferative disease,
- Sickle cell disease
- New York Heart Association (NYHA) grade III or IV heart failure;
• Febrile illness or acute infection between screening and Day 1 (to be checked on Day 1 prior to dosing);
• Body temperature ≥ 38°C at screening or prior to treatment on Day 1 (to be checked on Day 1 prior to dosing);
• History of Evan’s syndrome;
• Participation in another clinical study during the last 3 months;
• Alcohol, drug, or medication abuse within one year before the study;
• Re-entry of subjects previously treated in the present study;
• Re-screening within 4 weeks after the preceding screening;
• Suspected inability (e.g., language problems) or unwillingness to comply with study procedures;
• Mental condition rendering the subject (or the subject’s legally acceptable representative[s]) unable to
understand the nature, scope and possible consequences of the study) ;
• Any condition that is likely to interfere with evaluation of the IMP or satisfactory conduct of the study;
• Employee at the study site, or spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse).

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the set of antibodies most frequently bound to RBCs in subjects experiencing clinically significant intravascular hemolysis. The presumptive hemolysis cases will be adjudicated by an independent Adjudication Committee to determine if the hemolysis represents clinically significant intravascular hemolysis. Most frequent antibodies are defined as those antibodies that are identified at day 3 as binding specific red cell antigens (determined using an antigen panel) in at least 4 subjects (out of 10 with clinically significant hemolysis).

E.5.1.1

Timepoint(s) of evaluation of this end point

Continously

E.5.2

Secondary end point(s)

Subjects with a platelet response (PR) defined as subjects having a platelet count increases at least once to ≥ 50 x 109/L within 6 days after the first infusion (i.e., up to and including Day 7).

E.5.2.1

Timepoint(s) of evaluation of this end point

6 days after the first infusion

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

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

Serbia

Turkey

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 patient.

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