A Safety, Efficacy and Pharmacokinetics Study of a Recomb... | NCT01662531

NCT01662531

ID	Type	Description	Link
2011-006032-23	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
rIX-FP	Experimental	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) will be administered by IV infusion as routine weekly prophylaxis and episodic treatment for bleeding episodes.	Biological: rIX-FP

Name	Type	Description	Arm Group Labels	Other Names
rIX-FP	Biological	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)	rIX-FP

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product	Incremental recovery (IU/dL/IU/kg) is defined as the FIX activity (IU/dL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method. Recovery values were baseline-corrected for pre-infusion plasma FIX activity. Incremental recovery was measured following a single intravenous dose of 50 IU/kg rIX-FP on Day 1. Analysis of previous FIX product was conducted at the beginning of the study in a subset of subjects who had no historical pharmacokinetic (PK) data of their previous FIX product. For the PK assessment, the previous FIX product was administered by IV infusion after approximately 4 days following the last FIX treatment, prior to any dosing of rIX-FP. The formal PK population consisted of subjects who received at least 1 dose of rIX-FP for PK assessment and for whom a sufficient number of analyzable PK samples had been obtained to permit the evaluation of the PK profile of rIX-FP.	30 minutes after infusion
Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product	FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.	Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)	AUClast following a single intravenous dose of 50 IU/kg rIX-FP or previous FIX product. FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.	Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product	FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. Clearance is normalized for body weight.

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects With Treatment-related Adverse Events		12 months
Number of Subjects Developing Antibodies Against rIX-FP	Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA).

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Program Director	CSL Behring	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
The Royal Children's Hospital, Melbourne		Parkville	Victoria	3052	Australia
The Children's Hospital at Westmead

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37522479	Derived	Alvarez-Roman MT, Merchan RD, Mellado RCR, Jimenez-Yuste V. Switching and increasing prophylaxis regimen with a genetically recombinant fusion of coagulation factor IX and albumin in haemophilia B: a case report. Curr Opin Hematol. 2023 Sep 1;30(5):175-179. doi: 10.1097/MOH.0000000000000775.
27583313	Derived

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	rIX-FP	Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) will be administered by IV infusion as routine weekly prophylaxis and episodic treatment for bleeding episodes. rIX-FP: Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All 27 subjects were included in the Safety, Pharmacokinetic and Efficacy populations.

Arm/Group Information

ID	Title	Description
BG000	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
BG001	Age 6 to <12 Years	Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00012 BG00115 BG00227

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0003.2± 1.70 BG0018.1± 1.41 BG0025.9± 2.93

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product

Incremental recovery (IU/dL/IU/kg) is defined as the FIX activity (IU/dL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method. Recovery values were baseline-corrected for pre-infusion plasma FIX activity. Incremental recovery was measured following a single intravenous dose of 50 IU/kg rIX-FP on Day 1. Analysis of previous FIX product was conducted at the beginning of the study in a subset of subjects who had no historical pharmacokinetic (PK) data of their previous FIX product. For the PK assessment, the previous FIX product was administered by IV infusion after approximately 4 days following the last FIX treatment, prior to any dosing of rIX-FP. The formal PK population consisted of subjects who received at least 1 dose of rIX-FP for PK assessment and for whom a sufficient number of analyzable PK samples had been obtained to permit the evaluation of the PK profile of rIX-FP.

PK Population

Posted

Mean

Standard Deviation

(IU/dL)/(IU/kg)

30 minutes after infusion

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG001	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG002	Age 6 to <12 Years	Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Units	Counts
Participants	OG00027 OG00112 OG00215

Title

Denominators

Categories

rIX-FP Assessment (n = 27, 12, 15)

Title	Measurements
	OG0001.0114± 0.22711 OG0010.9506± 0.20432 OG0021.0600± 0.23934

Previous FIX Assessment (n = 17, 8, 9)

Primary

Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product

FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.

PK Population

Posted

Mean

Standard Deviation

hours

Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG001	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG002	Age 6 to <12 Years	Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Primary

Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)

AUClast following a single intravenous dose of 50 IU/kg rIX-FP or previous FIX product.

FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.

PK Population

Posted

Mean

Standard Deviation

IU*hr/dL

Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG001	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG002	Age 6 to <12 Years

Primary

Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product

FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. Clearance is normalized for body weight.

PK Population

Posted

Mean

Standard Deviation

mL/hr/kg

Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG001	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG002	Age 6 to <12 Years	Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Primary

Number of Subjects Developing Inhibitors to Factor IX (FIX)

Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting.

Safety Population

Posted

Number

participants

12 months

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Units	Counts
Participants	OG000

Secondary

Number of Subjects With Treatment-related Adverse Events

Safety Population

Posted

Number

participants

12 months

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Units	Counts
Participants	OG00027

Secondary

Number of Subjects Developing Antibodies Against rIX-FP

Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA).

Safety Population

Posted

Number

participants

12 months

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Units	Counts
Participants	OG000

Secondary

Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis

For each bleeding episode that required treatment, the number of episodes that required one, two or more than two infusions of rIX-FP to achieve hemostasis

Efficacy Population

Posted

Number

bleeding episodes

Approximately 12 months

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG001	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG002	Age 6 to <12 Years	Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Secondary

Consumption of rIX-FP During Routine Prophylaxis

Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.

Efficacy Population

Posted

Mean

Standard Deviation

IU/kg/month

12 months

ID	Title	Description
OG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG001	Age < 6 Years	Subjects less than 6 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.
OG002	Age 6 to <12 Years	Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	rIX-FP	All subjects received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study. Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.			4	27	23	27

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Forearm fracture	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected27 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected27 at risk
Tongue injury	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected27 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected27 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected27 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Contusion	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0009 events5 affected27 at risk
Injury	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0004 events2 affected27 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (14.1)	Systematic Assessment	EG0004 events4 affected27 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Headache	Nervous system disorders	MedDRA (14.1)	Systematic Assessment	EG0004 events2 affected27 at risk
Pyrexia	General disorders	MedDRA (14.1)	Systematic Assessment	EG00014 events9 affected27 at risk
Dental discomfort	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Toothache	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Vomiting	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG0003 events3 affected27 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Nasopharyngitis	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0006 events4 affected27 at risk
Bronchitis	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0004 events3 affected27 at risk
Ear infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0004 events3 affected27 at risk
Gastroenteritis	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0003 events3 affected27 at risk
Pharyngitis	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0003 events2 affected27 at risk
Viral infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0003 events2 affected27 at risk
Molluscum contagiosum	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected27 at risk

ID	Term
D002836	Hemophilia B

Ancestor Terms

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D040181	Genetic Diseases, X-Linked

ID	Term
C000618231	albutrepenonacog alfa

Subjects between 6 and less than 12 years of age who received a single dose of 50 IU/kg rIX-FP on Day 1 during the pharmacokinetic phase of the study.

Subjects received weekly (7-day) routine prophylaxis treatment with an initial weekly dose of 35 to 50 IU/kg rIX-FP, which may have been adjusted based on protocol-specified criteria.

Title

Denominators

Categories

Any adverse event

Title	Measurements
	OG00026

Treatment-related adverse event

Title	Measurements
	OG0000