Clinical Trials Register

Summary
EudraCT Number:	2010-020113-85
Sponsor's Protocol Code Number:	CSLCT-BIO-l0-67
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-05-30
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

Germany - PEI

A.2

EudraCT number

2010-020113-85

A.3

Full title of the trial

A Multicentre, Interventional, Non-randomized, Open-label, Single-group Phase III Study to evaluate Plasma-Derived Antihaemophilic Factor/von Willebrand Factor Concentrate (Biostate®) for Immune Tolerance Induction in Male Paediatric Subjects with Haemophilia A (≤2%) who have Developed High-titre Antibodies to Factor VIII (Factor VIII Inhibitors).

A.3.1

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

This is a clinical study to investigate how well Biostate works in treatment
of male patients below the age of 12 years who have a clotting factor
deficiency that is aggravated by the development of antibodies. The
antibodies are directed against the clotting factor that is given for
replacement therapy and usually make therapy unsuccessful. The
treatment used in this study is called immune tolerance therapy

A.3.2

Name or abbreviated title of the trial where available

SWIFT-ITI

A.4.1

Sponsor's protocol code number

CSLCT-BIO-l0-67

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/164/2009

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	Simone Lang
B.5.3	Address:
B.5.3.1	Street Address	Emil-von-Behring-Str. 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	00496421397060
B.5.5	Fax number	00496421393870
B.5.6	E-mail	Simone.Lang@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	No
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Biostate
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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.IMP: 2
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.3.1	Product name	Biostate
D.3.4	Pharmaceutical form	Lyophilisate and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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

Male paediatric subjects with Haemophilia A who develped high titre
antibodies to human coagulation Factor VIII

E.1.1.1

Medical condition in easily understood language

Treatment of patients with hereditary deficiency of blood coagulation
factor VIII that developed neutralizing antibodies against Factor VIII is
investigated

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10018941
E.1.2	Term	Haemophilia NOS
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the proportion of subjects who achieve a complete
response (success) following ITI treatment with Biostate.

E.2.2

Secondary objectives of the trial

Secondary Objective:
To assess the safety of Biostate when administered to subjects with
haemophilia A and inhibitors to FVIII in an ITI treatment regimen.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male subjects diagnosed with haemophilia A (::;2% FVIII level in the
absence of factor replacement, according to their medical history).
2. Age 28 days to <12 years.
3. ITI treatment can be initiated if:
a. An inhibitor level of >5 and <200 BU/mL was confirmed in 2 repeated
tests by the central laboratory during the screening period and no
waiting period is required as judged by the investigator.
b. An inhibitor level of >5 and <200 BU/mL was confirmed in 2 repeated
tests by the central laboratory during the screening period and the
inhibitor titre decreased from the peak titre during a waiting period
(maximum 11 months) added at the discretion of the investigator.
c. A subject has pre-existing inhibitors, determined no more than 11
months prior to the Screening visit, which decreased from the peak titre,
and an inhibitor level of >5 and <200 BU/mL was confirmed in 2
repeated tests by the central laboratory during the screening period. A
waiting period could still be added if the total duration from inhibitor
XML File Identifier: vFDreSBztfLwGbRZGET6u4sLSvo=
Page 14/26
diagnosis until start of IT! treatment (ie, including the screening period)
does not exceed 12 months.
4. The subject and/or his legally acceptable representative understand
the nature of the study and have given written informed consent to
participate in the study.
5. Sufficient peripheral venous access or central venous line.

E.4

Principal exclusion criteria

Exclusion Criteria:
l.DThe subject has received IT! previously.
2.DSubjects with a historical peak inhibitor titre of ~200 BU/mL.
3.DConcomitant treatment with drugs with immunosuppressive side
effects (eg, systemic cortlcosteroids), azathioprine, cyclophosphamide,
high dose immunoglobulin or the use of a protein A column or
plasmapheresis and interferons.
4.DHigh risk of cardiovascular, cerebrovascular, or other
thromboembolic events (excluding catheter thrombosis) as judged by
the investigator.
5. DSubjects who are human immunodeficiency virus (HIV)-l or HIV-2
positive (as reported in the medical records or determined at screening).
6.DThe subject has evidence or a history (within the previous 12
months) of abuse of any drug substance, licit or illicit.
7.DThe subject has a known or suspected hypersensitivity or has
previous evidence of severe side effects to von Willebrand factor
(VWF)/FVIII or FVIII concentrates or human albumin.
S.DThe subject has participated in a clinical study or used an
investigational compound (eg, a new chemical entity not approved for
clinical use) in the past 3 months, unless the study was for haemophilia
A and the subject developed an inhibitor (then, a wash-out period of at
least 4 weeks must be applied), or is planning to enter such a study
during the study period.
9.DSubjects or legal guardians/ representatives with suspected inability
(eg, language problems) or unwillingness to comply with study
procedures.
10.DThe subject has an acute or chronic medical condition other than
haemophilia A, which may, in the opinion of the investigator, affect the
conduct of the study.
l1.DMental condition rendering the subject (or the subject's legally
acceptable representative) unable to understand the nature, scope and
possible consequences of the study).
12.DAny condition that is likely to interfere with evaluation of the
investigational medicinal product (IMP) or satisfactory conduct of the
study.
13.DEmployee at the study site, or spouse/partner or relative of the
investigator or subinvestigators.
Study Product, Dose, and Mode of Administration:
The IMP Biostate will be intravenously (I.v.) administered at a daily dose
of 200 international units (IU)/kg body weight (b.w.), preferably split
into 2 doses of 100 IU/kg b.w. per day.
For subjects with an undetectable inhibitor titre «0.6 BU/mL) at 2
consecutive assessments, tested at intervals of 2 weeks (±3 days), and
normal recovery (~66% of predicted) for 6-S weeks, the daily Biostate
dose will be reduced by 20 IU/kg b.w. (ie, by 10% of the initial daily ITI
dose), if possible, every 2-4 weeks down to a dose of 100 IU/kg b.w.,
provided the recovery remains normal during that time (assessed
weekly).
After further gradual reduction of the dose and extension of the administration interval (at the discretion of the investigator), Biostate
will be administered as prophylaxis at a daily dose of 50 IU/kg b.w, on 3
days per week (about every second day).
Any daily dose'~100IU/kg b.w. should preferably be evenly split into 2
doses per day. Daily doses of 100 IU/kg b.w. or lower will be
administered once daily.
Bleeding complications during the tolerization period should be treated
according to centre's standard of care. Study treatment should not be
interrupted for surgical procedures.

E.5 End points

E.5.1

Primary end point(s)

Study endpoints:
Efficacy endpoints:
eoResponse to ITI treatment: complete response (success), partial
response (partial success), or ITI failure.
eoFVIII inhibitor titre.
eOTime to complete response (success).
eOTime to inhibitor <0.6 BU/mL for the first time.
Safety endpoints:
eAdverse events (AEs).
eClinical significant changes of laboratory testing (haematology,
biochemistry) as judged by the investigator.
eMarkers of activation of coagulation (thrombin-antithrombin complex
[TAT]) above ULN
eSymptomatic thromboembolic events including catheter thrombosis
eFrequency and nature of bleeding events (severity and number of
bleedings per patient).
eCatheter-related complications (line infections).
ePhysical examination and orthopaedic status.
eClinically significant changes of Vital signs (blood pressure, heart rate,
and body temperature).

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.2.3

Other

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

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

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)

After study participation the patients will be treated with the current
standard therapy on the discretion of their treating doctor.It is
expected at the end of the study Biostate will be licensed.

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

2011-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-08-15

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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