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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02053792




Registration number
NCT02053792
Ethics application status
Date submitted
29/01/2014
Date registered
4/02/2014
Date last updated
14/07/2022

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
Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)
Timepoint [1] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
Primary outcome [2] 0 0
Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs)
Timepoint [2] 0 0
Approximately 30 minutes after infusion of CSL654
Secondary outcome [1] 0 0
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs)
Timepoint [1] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [2] 0 0
Spontaneous ABR by Prophylaxis Regimen in PTPs
Timepoint [2] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [3] 0 0
Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.
Timepoint [3] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
Secondary outcome [4] 0 0
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE
Timepoint [4] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
Secondary outcome [5] 0 0
Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs
Timepoint [5] 0 0
Up to 3 years or the time it takes to achieve 50 EDs
Secondary outcome [6] 0 0
Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Timepoint [6] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [7] 0 0
Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Timepoint [7] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [8] 0 0
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Timepoint [8] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [9] 0 0
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Timepoint [9] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [10] 0 0
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Timepoint [10] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary outcome [11] 0 0
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Timepoint [11] 0 0
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

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
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/06/2021
Sample size
Target
Accrual to date
Final
97
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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02053792