Clinical Trials Register

Summary
EudraCT Number:	2022-002333-34
Sponsor's Protocol Code Number:	CSL654_3004
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2024-05-01
Trial 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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

Expand All Collapse All

A. Protocol Information

A.2

EudraCT number

2022-002333-34

A.3

Full title of the trial

A Phase 3, Open-label, Multicenter, Pharmacokinetics, Efficacy, and Safety Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Chinese Subjects with Hemophilia B

A.3.1

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

Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in Chinese subjects with hemophilia B previously treated with FIX therapy

A.4.1

Sponsor's protocol code number

CSL654_3004

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	Trial Registration Coordinator
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	16108784000
B.5.6	E-mail	clinicaltrials@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	Idelvion®
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	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	rIX-FP or CSL654
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	Albutrepenonacog alfa
D.3.9.2	Current sponsor code	rIX-FP or CSL654
D.3.9.4	EV Substance Code	SUB174139
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	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Albutrepenonacog alfa
D.3.9.2	Current sponsor code	rIX-FP or CSL654
D.3.9.4	EV Substance Code	SUB174139
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Albutrepenonacog alfa
D.3.9.2	Current sponsor code	rIX-FP or CSL654
D.3.9.4	EV Substance Code	SUB174139
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Albutrepenonacog alfa
D.3.9.2	Current sponsor code	rIX-FP or CSL654
D.3.9.4	EV Substance Code	SUB174139
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Albutrepenonacog alfa
D.3.9.2	Current sponsor code	rIX-FP or CSL654
D.3.9.4	EV Substance Code	SUB174139
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	3500
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

Hemophilia B is an X-linked recessive inherited bleeding disorder resulting from a deficiency of coagulation factor IX (FIX), a coagulation factor central to the process of blood coagulation

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	20.0
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	10010331 - Congenital, familial and genetic 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 evaluate the PK of 50 IU/kg rIX-FP in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%) during the Single-dose PK Period, to evaluate the efficacy of routine prophylaxis dosing with rIX-FP in preventing spontaneous bleeding episodes in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%), and to evaluate the safety of routine prophylaxis dosing with rIX-FP in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%) with respect to the development of inhibitors to FIX.

E.2.2

Secondary objectives of the trial

To further evaluate the PK of 50 IU/kg rIX-FP in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%) during the Single-dose PK Period, to evaluate the PK of 50 IU/kg rIX-FP in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%) during the Repeat PK Period, to further evaluate the efficacy of rIX-FP in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%), and to further evaluate the safety of rIX-FP in Chinese PTPs with hemophilia B (FIX activity of ≤ 2%).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male Chinese subjects aged ≤ 70 years
• Subjects with documented severe or moderately severe hemophilia B (FIX activity of ≤ 2%)
• Subjects have received FIX products for ≥ 150 exposure days (EDs) (subjects aged ≥ 6 years) or ≥ 50 EDs (subjects aged < 6 years)
• Subjects have no confirmed prior history of FIX inhibitor formation

E.4

Principal exclusion criteria

• Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein.
• Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
• Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
• Currently receiving a long-acting recombinant FIX treatment such as coagulation factor IX (recombinant), Fc fusion protein (Alprolix®).
• Use of traditional or herbal Chinese medicine(s) with an impact on hemophilia, including coagulation, within 28 days before Day 1 and / or refusal to abstain from these during the study until the end of the subject’s participation in the study.

E.5 End points

E.5.1

Primary end point(s)

1. Incremental recovery (IR) (plasma FIX activity)
2. Maximum plasma concentration (Cmax)
3. Terminal elimination half-life (t1/2) of rIX-FP
4. Area under the concentration-time curve (AUC)
5. Clearance (Cl) of rIX-FP
6. Annualized spontaneous bleeding rate (AsBR)
7. Number of subjects who develop an inhibitor to FIX

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1
2, 3, 4, and 5. Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
6. Up to 18 months
7. Up to 18 months after rIX-FP infusion

E.5.2

Secondary end point(s)

1. Percentage of area under the concentration-time curve extrapolated (%AUCExt)
2. Area under the first moment versus time curve extrapolated to infinity (AUMC0-∞)
3. Mean residence time (MRT)
4. Apparent volume of distribution during the terminal phase (Vz)
5. Apparent volume of distribution at steady-state (Vss)
6. Time to reach Cmax (Tmax)
7. Elimination rate constant (λz)
8. Incremental recovery (IR) (plasma FIX activity) - Repeat PK
9. Maximum plasma concentration (Cmax) - Repeat PK
10. Terminal elimination half-life (t1/2) of rIX-FP - Repeat PK
11. Area under the concentration-time curve (AUC) - Repeat PK
12. Clearance (Cl) of rIX-FP - Repeat PK
13. Annualized bleeding rate (ABR)
14. Annualized joint bleeding rate (AjBR)
15. Clinical evaluation of hemostatic efficacy for major bleeding episodes
16. Change in target joints
17. Consumption of rIX-FP - number of rIX-FP infusions (doses)
18. Consumption of rIX-FP - IU/kg per subject per month
19. Consumption of rIX-FP - IU/kg per subject per year
20. Number of bleeding episodes requiring rIX-FP to achieve hemostasis
21. Percentage of bleeding episodes requiring rIX-FP to achieve hemostasis
22. Number of subjects who develop antibodies against rIX-FP
23. Number of subjects who develop antibodies against Chinese hamster ovary host cell protein
24. The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP
25. The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 3, 4, 5, 6 and 7. Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
8. Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26
9, 10, 11 and 12. Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
13, 14, 15, 17, 18, 19, 20, 21, 24 and 25. Up to 18 months after rIX-FP infusion
16, 22 and 23. At baseline and up to 18 months after rIX-FP infusion

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)

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

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

China

E.8.7

Trial has a data monitoring committee

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.8.9.2

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

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)

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

This clinical trial will be conducted in adults and also in children in different age groups including children younger than 12 years of age.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

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)

None

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	China

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