Clinical Trials Register

Summary
EudraCT Number:	2012-003599-38
Sponsor's Protocol Code Number:	261201
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-15
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2012-003599-38

A.3

Full title of the trial

A Phase 2/3, Multi-Center, Open Label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (BAX 855) Administered for Prophylaxis and Treatment of Bleeding in Previously Treated Patients with Severe Hemophilia A

II./III. fázisú, multicentrikus, nyílt vizsgálat a vérzés megelőzésére és kezelésére alkalmazott pegilált rekombináns VIII. faktor (BAX 855) hatásosságának, biztonságosságának és farmakokinetikájának értékelésére korábban kezelt, súlyos hemofília A-ban szenvedő betegek esetében.

A.3.1

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

A study of the Safety and Effectiveness of PEGylated Recombinant Factor VIII (BAX 855) Administered for Prevention and Treatment of Bleeding in Previously Treated Patients with Severe Hemophilia A (a blood clotting disorder).

A.3.2

Name or abbreviated title of the trial where available

PEGylated rFVIII (BAX 855) in Hemophilia A

A.4.1

Sponsor's protocol code number

261201

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01736475

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/72/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Baxter 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	Baxter 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	Baxter Innovations GmbH
B.5.2	Functional name of contact point	Dikla Sharon
B.5.3	Address:
B.5.3.1	Street Address	Wagramerstraße 17-19
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	A-1220
B.5.3.4	Country	Austria
B.5.6	E-mail	dikla_sharon@baxter.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Advate 1000 IU powder and solvent for solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter AG
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	Advate
D.3.2	Product code	rAHF-PFM
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OCTOCOG ALFA
D.3.9.1	CAS number	139076-62-3
D.3.9.4	EV Substance Code	SUB16449MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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.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	PEGylated rFVIII
D.3.2	Product code	BAX 855 500IU/vial
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	BAX 855
D.3.9.3	Other descriptive name	BAX 855 (PEGYLATED RFVIII)
D.3.9.4	EV Substance Code	SUB90763
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	Yes
D.3.11.13.1	Other medicinal product type	Recombinant product with covalently bound polyethyleneglycol.
D.IMP: 3
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	PEGylated rFVIII
D.3.2	Product code	BAX 855 1000IU/vial
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	BAX 855
D.3.9.3	Other descriptive name	BAX 855 (PEGYLATED RFVIII)
D.3.9.4	EV Substance Code	SUB90763
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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	Yes
D.3.11.13.1	Other medicinal product type	Recombinant product with covalently bound polyethyleneglycol.

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

Severe hemophilia A (FVIII <1%)

súlyos hemofília A

E.1.1.1

Medical condition in easily understood language

Hemophilia A

hemofília A

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	LLT
E.1.2	Classification code	10060612
E.1.2	Term	Hemophilia A
E.1.2	System Organ Class	100000004850

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 efficacy and safety, including immunogenicity of BAX 855 administered as prophylaxis and as on-demand therapy in adolescent (12- <18 years) and adult (≥18 to 65 years) PTPs with severe hemophilia A. The primary objective is to compare the annualized rates of bleeding episodes (ABR) between subjects receiving a prophylactic dosing regimen of BAX 855 with an on-demand treatment regimen.
To determine the pharmacokinetic (PK) parameters of BAX 855

E.2.2

Secondary objectives of the trial

•To characterize the success of BAX 855 for treatment of bleeding episodes through the number of BAX 855 infusions needed for the treatment of a bleeding episode and through the length of intervals between bleeding episodes
•To compare the total weight-adjusted consumption of BAX 855 for each regimen
•To determine the immunogenicity of BAX 855
•To determine the safety of BAX 855
•To determine the PK parameters of BAX 855 following initial and repeat administration
•To assess Health-Related Quality of Life (HRQoL) over time for subjects receiving BAX 855

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Subject and/or legal representative has/have voluntarily provided signed informed consent
•Subject is 12 to 65 years old at the time of screening
•Subject is male with severe hemophilia A (FVIII clotting activity <1%) as confirmed by central laboratory at screening after the appropriate washout period or a documented FVIII clotting activity <1%
•Subject has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥150 documented exposure days (EDs)
•Subject is currently receiving prophylaxis or on-demand therapy with FVIII
•Subject has a Karnofsky performance score of ≥ 60 at screening
•Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count >200 cells/mm3, as confirmed by central laboratory at screening
•Subject is hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis
•Subject is willing and able to comply with the requirements of the protocol

E.4

Principal exclusion criteria

•Subject has detectable FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
•Subject has a history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the Bethesda assay or ≥ 0.6 BU using the Bethesda assay) at any time prior to screening
•Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand’s disease)
•Subject has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80
•Subject has severe chronic hepatic dysfunction [eg, ≥5 times upper limit of normal alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or a documented INR > 1.5]
•Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening
•Subject has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or is scheduled to use of such drugs during study participation
•Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
•Subject has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
•Subject is a family member or employee of the investigator

E.5 End points

E.5.1

Primary end point(s)

Prophylaxis will be considered to be successful if the upper limit of the 95% CI for the ratio between treatment means (A vs B) does not exceed 0.5 (corresponding to a 50% reduction of the mean ABR compared to the on-demand treatment).

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately 50 EDs or approximately 6 months (±2 weeks) for the prophylaxis arm and after 6 months (± 2 weeks) for the on-demand arm.

E.5.2

Secondary end point(s)

Success will be defined at a rating of excellent or good using the Efficacy Rating Scale for Treatment of Bleeding Episodes.

E.5.2.1

Timepoint(s) of evaluation of this end point

Approximately 50 EDs or approximately 6 months (±2 weeks) for the prophylaxis arm and after 6 months (± 2 weeks) for the on-demand arm.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

parallel factorial design

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

Australia

Austria

Belgium

Bulgaria

Czech Republic

France

Germany

Hong Kong

India

Israel

Japan

Korea, Republic of

Lithuania

Malaysia

Netherlands

Poland

Romania

Russian Federation

Spain

Sweden

Switzerland

Taiwan

Thailand

Ukraine

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 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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

102

F.1.3

Elderly (>=65 years)

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

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

105

F.4.2.2

In the whole clinical trial

132

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)

Continue with the expected normal treatment for Hemophilia A

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-07-17

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