Clinical Trials Register

Summary
EudraCT Number:	2011-002415-28
Sponsor's Protocol Code Number:	CSL654_3001
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-24
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

Germany - PEI

A.2

EudraCT number

2011-002415-28

A.3

Full title of the trial

A Phase II/III Open-label, Multicenter, Safety and Efficacy Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects with Hemophilia B

A.3.1

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

A Safety and Efficacy Study of a Recombinant Fusion Protein Linking
Coagulation Factor IX with Albumin (rIX-FP) in Patients with Hemophilia B

A.4.1

Sponsor's protocol code number

CSL654_3001

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/251/2011

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
B.5.2	Functional name of contact point	Global Project Leader
B.5.3	Address:
B.5.3.1	Street Address	1020 First Ave
B.5.3.2	Town/ city	King of Prussia, PA
B.5.3.3	Post code	19406
B.5.3.4	Country	United States
B.5.4	Telephone number	+16108784751
B.5.5	Fax number	+16103062450
B.5.6	E-mail	grace.cole@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.2.5	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 /09/ 723
D.3 Description of the IMP
D.3.1	Product name	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
D.3.2	Product code	CSL654
D.3.4	Pharmaceutical form	Powder for 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	CSL654 or rIX-FP
D.3.9.3	Other descriptive name	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin
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	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	Yes
D.2.5.1	Orphan drug designation number	EU/ 3/09/723
D.3 Description of the IMP
D.3.1	Product name	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
D.3.2	Product code	CSL654
D.3.4	Pharmaceutical form	Powder for 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	CSL654 or rIX-FP
D.3.9.3	Other descriptive name	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin
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: 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/723
D.3 Description of the IMP
D.3.1	Product name	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
D.3.2	Product code	CSL654
D.3.4	Pharmaceutical form	Powder for 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	CSL654 or rIX-FP
D.3.9.3	Other descriptive name	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin
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	2000
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hemophilia B

E.1.1.1

Medical condition in easily understood language

A study on prophylaxis and treatment of a non-plasma source (recombinant) product that replaces the missing clotting factor IX in patients with sever Hemophilia B.

E.1.1.2

Therapeutic area

Body processes [G] - Genetic Phenomena [G05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10060614
E.1.2	Term	Hemophilia B (Factor IX)
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

The primary objectives of the study are to evaluate the efficacy of rIX-FP in preventing bleeding episodes (prophylaxis) and safety of rIX-FP with respect to the development of inhibitors to FIX in patients with severe hemophilia B.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are:
•To evaluate the safety of rIX-FP, based on AEs and the development of antibodies to rIX-FP.
•To evaluate the clinical response to rIX-FP for the prevention and treatment of bleeding episodes in patients with severe hemophilia B.
•To evaluate the efficacy of rIX-FP in surgical prophylaxis.
•To evaluate the pharmacokinetics (PK) of a single dose of rIX-FP.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

The primary objective of the sub-study is to evaluate the efficacy of rIXFP in the prevention and control of bleeding in patients with severe to moderate hemophilia B during surgical procedures.
The secondary objective of the study is to evaluate the safety of rIX-FP during the intraoperative and postoperative periods.

E.3

Principal inclusion criteria

• Male subjects, 12 to 65 years old.
• Severe hemophilia B (FIX activity of ≤ 2%).
• Subjects who have received FIX products (plasma-derived and/or
recombinant FIX) for > 150 exposure days (EDs).
• No history of FIX inhibitor formation, no detectable inhibitors at
Screening and no family history of inhibitors against FIX.
• Written informed consent for study participation.
• On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months.

E.4

Principal exclusion criteria

• Known hypersensitivity to any FIX product or hamster protein.
• Known congenital or acquired coagulation disorder other than
congenital FIX deficiency.
• HIV positive subjects with a CD4 count < 200/mm3.
• Low platelet count, kidney or liver dysfunction.
• Recent life-threatening bleeding episode.

E.5 End points

E.5.1

Primary end point(s)

Change in frequency of spontaneous bleeding events between ondemand and prophylaxis treatments (annualized)

E.5.1.1

Timepoint(s) of evaluation of this end point

approximately 14 months

E.5.2

Secondary end point(s)

- The frequency of related Adverse Events (AEs) to rIX-FP over the course of the study.
- The number of subjects with FIX inhibitors.
- The number of subjects with antibodies against rIX-FP.
- Proportion of bleeding episodes requiring one or ≤ two infusions of rIX-FP to achieve hemostasis.
- Investigator’s overall clinical assessment of hemostatic efficacy for treatment of bleeding episodes, based on a four point
ordinal scales (excellent, good, moderate, poor/ none).
- rIX-FP consumed per month while maintaining assigned prophylactic treatment interval during routine prophylaxis.
- Incremental recovery (IU/mL/IU/kg) at 30 minutes following infusion of rIX-FP.
- Half-life (t1/2) of a single dose of rIX-FP.
- AUC to the last sample with quantifiable drug concentration (AUC0-t) of a single dose of rIX-FP.
- Clearance of a single dose of rIX-FP.
- Annualized spontaneous bleeding events during the 7 day prophylactic regimen period compared to the annualized spontaneous bleeding events during each of the prophylactic regimens longer than the 7 day prophylactic regimen period.
- Investigator’s (or surgeon’s) overall clinical assessment of hemostatic efficacy for surgical prophylaxis, based on a four point
ordinal scale (excellent, good, moderate, poor/ none)

E.5.2.1

Timepoint(s) of evaluation of this end point

All timepoints are approximately 14 months except for the PK endpoints, which are 240 hours or as indicated in the endpoint description, and the Investigator's overall clinical assessment of hemostatic efficacy for surgical prophylaxis, which is approximately 14 days.

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

Different treatment schedule -On demand arm (as detailed in the protocol)

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

Bulgaria

France

Italy

Japan

Austria

Germany

Spain

Israel

Russian Federation

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

The end of study participation for an individual subject occurs with the end of the follow-up period, which is defined as completion of the final study visit, after which no further study-related procedures will be performed.

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

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:

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

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

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)

Patients who end their participation in the trial can return to standard therapy according to their health care scheme. There are several other recombinant Factor IX products available on the market.

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

2011-11-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-07-21

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