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A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B

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ClinicalTrials.gov Identifier: NCT01662531
Recruitment Status : Completed
First Posted : August 10, 2012
Results First Posted : May 9, 2016
Last Update Posted : May 9, 2016
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia B
Intervention Biological: rIX-FP
Enrollment 27
Recruitment Details Of the 18 sites that were activated, subjects were enrolled from 17 sites in 10 countries.
Pre-assignment Details Subjects <12 years of age with severe hemophilia B (FIX activity of ≤2%) were planned to be enrolled in the study, including 11 to 12 subjects in each age group (6 to <12 years and <6 years of age). Of 29 subjects screened, 27 subjects were enrolled and treated with rIX-FP.
Arm/Group Title rIX-FP
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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)

Period Title: Overall Study
Started 27
Completed 27
Not Completed 0
Arm/Group Title Age < 6 Years Age 6 to <12 Years Total
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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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 12 15 27
Hide Baseline Analysis Population Description
All 27 subjects were included in the Safety, Pharmacokinetic and Efficacy populations.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 15 participants 27 participants
3.2  (1.70) 8.1  (1.41) 5.9  (2.93)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 15 participants 27 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
12
 100.0%
15
 100.0%
27
 100.0%
1.Primary Outcome
Title Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Hide Description 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.
Time Frame 30 minutes after infusion
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PK Population
Arm/Group Title rIX-FP Age < 6 Years Age 6 to <12 Years
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 27 12 15
Mean (Standard Deviation)
Unit of Measure: (IU/dL)/(IU/kg)
rIX-FP Assessment (n = 27, 12, 15) 1.0114  (0.22711) 0.9506  (0.20432) 1.0600  (0.23934)
Previous FIX Assessment (n = 17, 8, 9) 0.7379  (0.19768) 0.6764  (0.13980) 0.7925  (0.23219)
2.Primary Outcome
Title Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Hide Description FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Time Frame Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
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Hide Analysis Population Description
PK Population
Arm/Group Title rIX-FP Age < 6 Years Age 6 to <12 Years
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 27 12 15
Mean (Standard Deviation)
Unit of Measure: hours
rIX-FP Assessment (n = 26, 11, 15) 91.4492  (15.9754) 89.6124  (11.17364) 92.7962  (19.02537)
Previous FIX Assessment (n = 16, 7, 9) 18.6291  (6.15551) 19.8816  (8.01073) 17.6550  (4.52497)
3.Primary Outcome
Title Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)
Hide Description

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.

Time Frame Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title rIX-FP Age < 6 Years Age 6 to <12 Years
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 27 12 15
Mean (Standard Deviation)
Unit of Measure: IU*hr/dL
rIX-FP Assessment (n = 27, 12, 15) 4156.7037  (1204.09549) 3891.4820  (1252.99415) 4368.8810  (1162.09967)
Previous FIX Assessment (n = 16, 7, 9) 718.9386  (230.52884) 676.5414  (316.91381) 751.9143  (146.70454)
4.Primary Outcome
Title Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Hide Description 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.
Time Frame Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title rIX-FP Age < 6 Years Age 6 to <12 Years
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 27 12 15
Mean (Standard Deviation)
Unit of Measure: mL/hr/kg
rIX-FP Assessment (n = 26, 11, 15) 1.1119  (0.31373) 1.1841  (0.32924) 1.0589  (0.30203)
Previous FIX Assessment (n = 16, 7, 9) 6.4007  (2.14434) 7.1576  (2.78944) 5.8119  (1.37641)
5.Primary Outcome
Title Number of Subjects Developing Inhibitors to Factor IX (FIX)
Hide Description Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting.
Time Frame 12 months
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Safety Population
Arm/Group Title rIX-FP
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
0
6.Secondary Outcome
Title Number of Subjects With Treatment-related Adverse Events
Hide Description [Not Specified]
Time Frame 12 months
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Hide Analysis Population Description
Safety Population
Arm/Group Title rIX-FP
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
Any adverse event 26
Treatment-related adverse event 0
7.Secondary Outcome
Title Number of Subjects Developing Antibodies Against rIX-FP
Hide Description Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA).
Time Frame 12 months
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Hide Analysis Population Description
Safety Population
Arm/Group Title rIX-FP
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
0
8.Secondary Outcome
Title Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis
Hide Description 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
Time Frame Approximately 12 months
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Efficacy Population
Arm/Group Title rIX-FP Age < 6 Years Age 6 to <12 Years
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 27 12 15
Measure Type: Number
Unit of Measure: bleeding episodes
1 infusion 94 40 54
2 infusions 9 5 4
> 2 infusions 3 0 3
1 or 2 infusions 103 45 58
9.Secondary Outcome
Title Consumption of rIX-FP During Routine Prophylaxis
Hide Description Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.
Time Frame 12 months
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Hide Analysis Population Description
Efficacy Population
Arm/Group Title rIX-FP Age < 6 Years Age 6 to <12 Years
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 27 12 15
Mean (Standard Deviation)
Unit of Measure: IU/kg/month
205.071  (41.1550) 213.517  (44.3848) 198.314  (38.5693)
Time Frame 12 months
Adverse Event Reporting Description Treatment-emergent adverse events, defined as adverse events present prior to the first dose of rIX-FP that subsequently worsened in severity or those that were not present prior to the first dose but subsequently appeared are summarized.
 
Arm/Group Title rIX-FP
Hide Arm/Group Description

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.

All-Cause Mortality
rIX-FP
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
rIX-FP
Affected / at Risk (%) # Events
Total   4/27 (14.81%)    
Injury, poisoning and procedural complications   
Forearm fracture  1  1/27 (3.70%)  1
Head injury  1  1/27 (3.70%)  1
Tongue injury  1  1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/27 (3.70%)  2
Groin pain  1  1/27 (3.70%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
rIX-FP
Affected / at Risk (%) # Events
Total   23/27 (85.19%)    
Blood and lymphatic system disorders   
Anaemia  1  2/27 (7.41%)  2
Gastrointestinal disorders   
Dental discomfort  1  2/27 (7.41%)  2
Diarrhoea  1  2/27 (7.41%)  2
Toothache  1  2/27 (7.41%)  2
Vomiting  1  2/27 (7.41%)  2
General disorders   
Pyrexia  1  9/27 (33.33%)  14
Infections and infestations   
Nasopharyngitis  1  4/27 (14.81%)  6
Bronchitis  1  3/27 (11.11%)  4
Ear infection  1  3/27 (11.11%)  4
Gastroenteritis  1  3/27 (11.11%)  3
Pharyngitis  1  2/27 (7.41%)  3
Viral infection  1  2/27 (7.41%)  3
Molluscum contagiosum  1  2/27 (7.41%)  2
Upper respiratory tract infection  1  2/27 (7.41%)  2
Injury, poisoning and procedural complications   
Contusion  1  5/27 (18.52%)  9
Injury  1  2/27 (7.41%)  4
Head injury  1  2/27 (7.41%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/27 (11.11%)  3
Pain in extremity  1  2/27 (7.41%)  2
Nervous system disorders   
Headache  1  2/27 (7.41%)  4
Respiratory, thoracic and mediastinal disorders   
Cough  1  4/27 (14.81%)  4
Oropharyngeal pain  1  2/27 (7.41%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: Clinical Trial Disclosure Manager
Organization: CSL Behring
Phone: Use email contact
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01662531     History of Changes
Other Study ID Numbers: CSL654_3002
2011-006032-23 ( EudraCT Number )
First Submitted: August 7, 2012
First Posted: August 10, 2012
Results First Submitted: April 3, 2016
Results First Posted: May 9, 2016
Last Update Posted: May 9, 2016