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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02053792




Registration number
NCT02053792
Ethics application status
Date submitted
29/01/2014
Date registered
4/02/2014
Date last updated
30/06/2020

Titles & IDs
Public title
A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
Scientific title
A Phase 3b Open-label, Multicenter, Safety and Efficacy Extension Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B
Secondary ID [1] 0 0
2012-005489-37
Secondary ID [2] 0 0
CSL654_3003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - rIX-FP

Experimental: rIX-FP - Subjects will administer rIX-FP by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 3 years.
The routine prophylaxis treatment interval for previously treated patients may be changed at each scheduled 6-month follow-up assessment. On-demand treatment with rIX-FP will be used for all bleeding episodes requiring treatment. Subjects (other than those in France) may participate in a surgical 'substudy' in which rIX-FP may be administered before, during and after surgery. An additional substudy will examine the safety and PK of subcutaneous administration of rIX-FP.
For previously untreated patients, subjects will administer rIX-FP intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter.
The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.


Other interventions: rIX-FP
Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Main study: Total number of subjects who develop inhibitors against factor IX (FIX)
Timepoint [1] 0 0
Approximately 5 years
Primary outcome [2] 0 0
Surgery substudy: Investigator's overall clinical assessment of hemostatic efficacy for surgical prophylaxis - Clinical assessment of hemostatic efficacy to be based on a four point ordinal scale (excellent, good, moderate, poor / none)
Timepoint [2] 0 0
Immediately after surgery (0 hours) and at up to 3 timepoints thereafter up to 72 hours or discharge, whichever is earliest.
Primary outcome [3] 0 0
Incremental recovery in previously untreated patients (PUPs) - Incremental recovery expressed as IU/dL per IU/kg
Timepoint [3] 0 0
Approximately 30 minutes after infusion
Secondary outcome [1] 0 0
Main study: Comparison of annualized bleeding rate between different prophylaxis treatment intervals. - Comparison of annualized bleeding rate by prophylaxis treatment interval for spontaneous treated bleeds and total treated bleeds.
Timepoint [1] 0 0
Approximately 5 years
Secondary outcome [2] 0 0
Main study: Comparison of annualized bleeding rate between 2 different prophylaxis treatment intervals and on-demand treatment. - For subjects from the lead-in study (CSL654_3001 [NCT01496274]), comparison of the annualized bleeding rate of spontaneous treated bleeds and total treated bleeds between routine prophylaxis treatment in this study (CSL654_3003) and:
On-demand treatment during the lead-in study (CSL654_3001).
Routine prophylaxis treatment with the different treatment interval used by the subject in the lead-in study (CSL654_3001).
Timepoint [2] 0 0
Approximately 5 years
Secondary outcome [3] 0 0
Main study: rIX-FP consumed per month per subject during routine prophylaxis treatment.
Timepoint [3] 0 0
Approximately 5 years
Secondary outcome [4] 0 0
Surgery substudy: The frequency of adverse events (AEs) related to rIX-FP
Timepoint [4] 0 0
28 days after surgery (major surgery) or up to hospital discharge (minor surgery)
Secondary outcome [5] 0 0
Surgery substudy: Total number of subjects who develop inhibitors against FIX
Timepoint [5] 0 0
28 days after surgery (major surgery) or up to hospital discharge (minor surgery)
Secondary outcome [6] 0 0
Surgery substudy: Total number of subjects who develop antibodies against rIX-FP.
Timepoint [6] 0 0
28 days after surgery (major surgery) or up to hospital discharge (minor surgery)
Secondary outcome [7] 0 0
Surgery substudy: Predicted and intraoperative estimated blood loss. - The predicted blood loss (mL) is based on blood loss expected from a non-hemophilic individual undergoing the same type / extent of procedure.
The estimated blood loss (mL) is the anesthesiologist's record of estimated blood loss during the procedure.
Timepoint [7] 0 0
Predicted blood loss and intraoperative estimated blood loss to be determined before surgery and at the end of surgery, respectively
Secondary outcome [8] 0 0
Surgery substudy: Predicted and actual transfusion requirements.
Timepoint [8] 0 0
Predicted and actual transfusion requirements to be determined before and at the end of surgery, respectively
Secondary outcome [9] 0 0
Surgery substudy: Change in hemoglobin levels between baseline, intraoperatively and postoperatively (major surgery only).
Timepoint [9] 0 0
Before, during and up to 28 days after surgery
Secondary outcome [10] 0 0
Overall adverse events (AEs) and rIX-FP-related AEs - The overall percentage of subjects with at least one AE, and the overall percentage of subjects with at least one rIX-FP-related AE
Timepoint [10] 0 0
Approximately 5 years
Secondary outcome [11] 0 0
Hemostatic response to rIX-FP treatment in PUPs - The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or poor/no response".
Timepoint [11] 0 0
Hemostatic response of rIX-FP treatment during the course of the study (up to 5 years)

Eligibility
Key inclusion criteria
Inclusion criteria:

Main study inclusion criteria:

For previously treated subjects, either:

- Completed a CSL-sponsored rIX-FP (CSL654) study, including study CSL654_3001
[NCT01496274] or study CSL654_3002 [NCT01662531].

Or:

- Scheduled to have a major non-emergency surgery within approximately 8 weeks from the
anticipated date of receiving the first rIX-FP injection.

- Not previously completed a CSL-sponsored rIX-FP lead-in study.

- Male, 12 to 70 years of age.

- Documented severe hemophilia B (FIX activity of = 2%), or confirmed at screening by
the central laboratory.

- Subjects who have received FIX products (plasma-derived and / or recombinant FIX) for
> 150 exposure days (EDs), confirmed by their treating physician.

- No confirmed history of FIX inhibitor formation at screening by the central laboratory

For previously untreated subjects:

- Male, up to 18 years of age.

- Documented severe hemophilia B (FIX activity of = 2%), or confirmed at screening by
the central laboratory.

- Never previously been treated with FIX clotting factor products (except previous
exposure to blood components).

- No confirmed history of FIX inhibitor formation

Surgery substudy inclusion criterion:

- Must require non-emergency surgery

Subcutaneous substudy inclusion criteria:

- Male, at least 18 years of age.

- Subjects currently enrolled in Study CSL654_3003

- Subjects who have received rIX-FP for = 100 EDs (single-dose cohorts) or for = 50 EDs
(repeated-dose cohort)
Minimum age
No limit
Maximum age
70 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Main study exclusion criteria:

- Currently receiving a therapy not permitted during the study.

- Any issue that, in the opinion of the investigator, would render the subject
unsuitable for participation in the study.

For subjects who have previously completed a CSL-sponsored rIX-FP study:

- Unwilling to participate in the study for a total of 100 exposure days.

For subjects requiring major non-emergency surgery who have not previously completed a
CSL-sponsored rIX-FP lead-in study:

- Known hypersensitivity (ie, allergic reaction or anaphylaxis) to any FIX product or
hamster protein.

- Known congenital or acquired coagulation disorder other than congenital FIX
deficiency.

- Currently receiving IV immunomodulating agents such as immunoglobulin or chronic
systemic corticosteroid treatment.

- Low platelet count, kidney or liver disease.

- Human immunodeficiency virus positive with a CD4 count < 200/mm3.

For previously untreated subjects:

- Known congenital or acquired coagulation disorder other than congenital FIX deficiency
(except for vitamin K deficiency of the newborn).

- Known kidney or liver dysfunction or any condition which, in the investigator's
opinion, place the patient at unjustifiable risk.

The surgical substudy does not have any additional exclusion criteria, although subject(s)
in France will not be eligible for the surgery sub-study.

Subcutaneous substudy exclusion criteria:

- Intravenous use of rIX-FP within 14 days of subcutaneous administration of rIX-FP.

- Life-threatening bleeding episode or major surgery during the 3 months prior to
substudy entry

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [2] 0 0
The Children's Hospital Westmead - Westmead
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Utah
Country [5] 0 0
Austria
State/province [5] 0 0
Vienna
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Sofia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Czechia
State/province [8] 0 0
Brno
Country [9] 0 0
Czechia
State/province [9] 0 0
Ostrava-Poruba
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha
Country [11] 0 0
France
State/province [11] 0 0
Brest
Country [12] 0 0
France
State/province [12] 0 0
Bron Cedex
Country [13] 0 0
France
State/province [13] 0 0
Le Kremlin-Bicetre
Country [14] 0 0
France
State/province [14] 0 0
Marseille Cedex
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Bonn
Country [17] 0 0
Germany
State/province [17] 0 0
Bremen
Country [18] 0 0
Germany
State/province [18] 0 0
Duisburg
Country [19] 0 0
Germany
State/province [19] 0 0
Dusseldorf
Country [20] 0 0
Germany
State/province [20] 0 0
Hamburg
Country [21] 0 0
Germany
State/province [21] 0 0
Hannover
Country [22] 0 0
Germany
State/province [22] 0 0
Heidelberg
Country [23] 0 0
Israel
State/province [23] 0 0
Tel Aviv
Country [24] 0 0
Italy
State/province [24] 0 0
Milano
Country [25] 0 0
Italy
State/province [25] 0 0
Parma
Country [26] 0 0
Italy
State/province [26] 0 0
Vicenza
Country [27] 0 0
Japan
State/province [27] 0 0
Kashihara
Country [28] 0 0
Japan
State/province [28] 0 0
Kitakyushu
Country [29] 0 0
Japan
State/province [29] 0 0
Nagoya
Country [30] 0 0
Japan
State/province [30] 0 0
Nishinomiya
Country [31] 0 0
Japan
State/province [31] 0 0
Tokyo
Country [32] 0 0
Japan
State/province [32] 0 0
Yokohama
Country [33] 0 0
Malaysia
State/province [33] 0 0
Kuala Lumpur
Country [34] 0 0
Philippines
State/province [34] 0 0
Cebu
Country [35] 0 0
South Africa
State/province [35] 0 0
Parktown
Country [36] 0 0
Spain
State/province [36] 0 0
A Coruna
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will examine the long-term safety and efficacy of rIX-FP for the control and
prevention of bleeding episodes in children and adults with severe hemophilia B. The study
will include subjects who have not previously been treated with Factor IX products, subjects
who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major
non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study.

A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with
hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy
will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.
Trial website
https://clinicaltrials.gov/show/NCT02053792
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Program Director
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications