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

• ClinicalTrials.gov Identifier: NCT01496274
• Recruitment Status: Completed
• First Posted: December 21, 2011
• Results First Posted: May 9, 2016
• Last Update Posted: May 9, 2016
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia B
• Intervention: Biological: rIX-FP
• Enrollment: 63

Participant Flow

Recruitment Details	Subjects were enrolled from 30 sites in 10 countries.
Pre-assignment Details	A total of 69 subjects provided informed consent and were screened for study participation. Of these, 63 subjects were enrolled and treated with rIX-FP.

Arm/Group Title	Prophylaxis	On-demand
Arm/Group Description	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Period Title: Overall Study
Started	40	23
Completed	37	18
Not Completed	3	5
Reason Not Completed
Protocol Violation	0	1
Adverse Event	1	1
Withdrawal by Subject	2	0
Lost to Follow-up	0	3

Baseline Characteristics

Arm/Group Title		Prophylaxis	On-demand	Total
Arm/Group Description		Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. rIX-FP: Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. rIX-FP: Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration	Total of all reporting groups
Overall Number of Baseline Participants		40	23	63
Baseline Analysis Population Description		Safety Population
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	40 participants	23 participants	63 participants
0 to 11 years		0	0	0
12 to 17 years		7	0	7
18 to 64 years		33	23	56
65 years and over		0	0	0
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	23 participants	63 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	40 100.0%	23 100.0%	63 100.0%

Outcome Measures

1. Primary Outcome

Title	Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized)
Description	Subjects in the on-demand arm received on-demand dosing with rIX-FP for up to 26 weeks (on-demand regimen), and then received weekly prophylaxis with rIX-FP for the remainder of the study (prophylaxis regimen). The effectiveness of prophylaxis in comparison to on-demand therapy was investigated by comparing the same subject's annualized spontaneous bleeding rate (AsBR) during the on-demand regimen and during the prophylaxis regimen.
Time Frame	Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen.

Outcome Measure Data

Analysis Population Description

This analysis includes only the participants assigned to the on-demand arm who received at least 1 dose of rIX-FP in the on-demand regimen and at least 1 dose of rIX-FP in the prophylaxis regimen.

Arm/Group Title	On-demand Arm, On-demand Regimen	On-demand Arm, Prophylaxis Regimen
Arm/Group Description:	Participants in the On-demand Arm, when receiving episodic treatment for bleeding episodes (on-demand regimen).	Participants in the On-demand Arm, when receiving routine weekly prophylaxis (prophylaxis regimen).
Overall Number of Participants Analyzed	19	19
Median (Inter-Quartile Range); Unit of Measure: bleeds/year/subject
	15.43; (7.98 to 17.96)	0.00; (0.00 to 0.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	On-demand Arm, On-demand Regimen, On-demand Arm, Prophylaxis Regimen
	Comments	A test of null hypothesis that the ratio of AsBR (prophylaxis regimen/on-demand regimen) was ≥ 0.50 was conducted at the 1-sided 0.025 level. Matched pairs design with 19 subjects and 2 observations per subject.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P value is based on a Wilcoxon signed-rank test of H0: AsBR ratio (prophylaxis regimen/on-demand regimen) ≥ 0.50. The ratio was based on the original scale.
	Method	Wilcoxon signed-rank test
	Comments	[Not Specified]

2. Primary Outcome

Title	Number of Subjects Developing Inhibitors Against Factor IX (FIX)
Description	The number of participants developing inhibitors against factor IX (FIX) along with the 95% Clopper-Pearson confidence interval, are summarized for subjects with 50 or more exposure days (EDs) to rIX-FP, and for all participants in the study.
Time Frame	Up to 27.7 months (maximum)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Safety Population
Arm/Group Description:	The Safety population consisted of subjects who received at least 1 dose of rIX-FP during the study.
Overall Number of Participants Analyzed	63
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
Participants with >=50 EDs to rIX-FP (n = 49)	0; (0.0 to 7.3)
All participants (n = 63)	0; (0.0 to 5.7)

3. Secondary Outcome

Title	The Frequency of Related Adverse Events
Description	The percentage of participants experiencing treatment-related adverse-events (TEAEs).
Time Frame	For the duration of the study; median 20.27 months.

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Prophylaxis	On-demand	Safety Population
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	The Safety population consisted of subjects who received at least 1 dose of rIX-FP during the study.
Overall Number of Participants Analyzed	40	23	63
Measure Type: Number; Unit of Measure: Percentage of participants
Related TEAE	10.0	4.3	7.9
Not related TEAE	87.5	78.3	84.1

4. Secondary Outcome

Title	Number of Subjects Developing Antibodies Against rIX-FP
Description	[Not Specified]
Time Frame	For the duration of the study; median 20.27 months.

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Safety Population
Arm/Group Description:	The Safety population consisted of subjects who received at least 1 dose of rIX-FP during the study.
Overall Number of Participants Analyzed	63
Measure Type: Number; Unit of Measure: participants
	0

5. Secondary Outcome

Title	Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis
Description	Number of injections required to achieve hemostasis expressed as a percentage of the bleeding episodes requiring treatment.
Time Frame	For the duration of the study; median 20.27 months.

Outcome Measure Data

Analysis Population Description

Efficacy Population

Arm/Group Title	Prophylaxis	On-demand Arm, On-demand Regimen	On-demand Arm, Prophylaxis Regimen
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Participants in the On-demand Arm, when receiving episodic treatment for bleeding episodes (on-demand regimen).	Participants in the On-demand Arm, when receiving routine weekly prophylaxis (prophylaxis regimen).
Overall Number of Participants Analyzed	40	23	19
Overall Number of Units Analyzed; Type of Units Analyzed: Bleeding episodes requiring treatment	101	220	37
Measure Type: Number; Unit of Measure: percentage of bleeding episodes treated
1 injection	92.1	94.5	91.9
1 or 2 injections	100.0	98.6	94.6

6. Secondary Outcome

Title	Investigator's Overall Clinical Assessment of Hemostatic Efficacy for Treatment of Bleeding Episodes, Based on a Four Point Ordinal Scales (Excellent, Good, Moderate, Poor/No Response)
Description	Number of bleeding episodes requiring treatment that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's clinical assessment of hemostatic efficacy, expressed as a percentage of the bleeding episodes requiring treatment.
Time Frame	For the duration of the study; median 20.27 months

Outcome Measure Data

Analysis Population Description

Efficacy Population

Arm/Group Title	Prophylaxis	On-demand
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Overall Number of Participants Analyzed	40	23
Overall Number of Units Analyzed; Type of Units Analyzed: Bleeding episodes requiring treatment	101	257
Measure Type: Number; Unit of Measure: percentage of bleeding episodes
Excellent	71.3	87.5
Good	20.8	7.4
Moderate	3.0	2.3
Poor/No response	0	0.4
Missing	5.0	2.3

7. Secondary Outcome

Title	rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis.
Description	Time frame: For Prophylaxis Arm 7-, 10- and 14-day regimens, median 269, 240 and 386 days respectively. For On-demand Arm, prophylaxis regimen, median 316 days.
Time Frame	Median 269, 240, 386 and 316 days, respectively (see Description)

Outcome Measure Data

Analysis Population Description

Efficacy Population

Arm/Group Title	On-demand Arm, Prophylaxis Regimen	Prophylaxis Arm, 7-day Regimen	Prophylaxis Arm, 10-day Regimen	Prophylaxis Arm, 14-day Regimen
Arm/Group Description:	Participants in the On-demand Arm, when receiving routine weekly prophylaxis (prophylaxis regimen).	Subjects received prophylactic rIX-FP on a weekly basis.	Subjects received prophylactic rIX-FP every 10 days.	Subjects received prophylactic rIX-FP every 14 days.
Overall Number of Participants Analyzed	19	40	7	21
Mean (Standard Deviation); Unit of Measure: IU/kg/month
	191.69 (36.33)	202.68 (47.92)	201.50 (42.56)	157.44 (16.34)

8. Secondary Outcome

Title	Incremental Recovery of rIX-FP
Description	Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame	336 hours

Outcome Measure Data

Analysis Population Description

The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP.

Arm/Group Title	Prophylaxis	On-demand
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Overall Number of Participants Analyzed	27	18
Mean (Standard Deviation); Unit of Measure: (IU/dL)/(IU/kg)
	1.29 (0.33)	1.24 (0.25)

9. Secondary Outcome

Title	Half-life (t1/2) of a Single Dose of rIX-FP
Description	PK data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame	336 hours

Outcome Measure Data

Analysis Population Description

The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP.

Arm/Group Title	Prophylaxis	On-demand
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Overall Number of Participants Analyzed	26	17
Mean (Standard Deviation); Unit of Measure: hour
	104.77 (22.73)	96.88 (20.94)

10. Secondary Outcome

Title	Area Under the Curve (AUC)
Description	AUC to the last sample with quantifiable drug concentration (AUClast) of a single dose of rIX-FP. PK data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame	336 hours

Outcome Measure Data

Analysis Population Description

The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP.

Arm/Group Title	Prophylaxis	On-demand
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Overall Number of Participants Analyzed	27	18
Mean (Standard Deviation); Unit of Measure: IU*hr/dL
	6534.15 (1856.96)	5963.30 (1893.00)

11. Secondary Outcome

Title	Clearance of a Single Dose of rIX-FP
Description	PK data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame	336 hours

Outcome Measure Data

Analysis Population Description

The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP.

Arm/Group Title	Prophylaxis	On-demand
Arm/Group Description:	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.	Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Overall Number of Participants Analyzed	26	17
Mean (Standard Deviation); Unit of Measure: mL/hr
	50.19 (12.92)	59.00 (19.37)

12. Secondary Outcome

Title	Investigator's (or Surgeon's) Overall Clinical Assessment of Hemostatic Efficacy for Surgical Prophylaxis, Based on a Four Point Ordinal Scale (Excellent, Good, Moderate, Poor/No Response)
Description	Number of surgical events treated prophylactically with rIX-FP that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's (surgeon's) overall assessment of hemostatic efficacy for surgical prophylaxis.
Time Frame	Up to 14 days after surgery

Outcome Measure Data

Analysis Population Description

Surgical Population

Arm/Group Title	Surgical Population
Arm/Group Description:	The Surgical population consisted of 3 subjects in the prophylaxis arm and 1 subject in the on demand arm who received at least 1 dose of rIX FP for a major or minor surgical procedure.
Overall Number of Participants Analyzed	4
Overall Number of Units Analyzed; Type of Units Analyzed: Events	6
Measure Type: Number; Unit of Measure: events
Excellent	6
Good	0
Moderate	0
Poor/No response	0

13. Secondary Outcome

Title	Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens
Description	Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.
Time Frame	During treatment, between median 240 and 386 days per subject.

Outcome Measure Data

Analysis Population Description

Efficacy Population

Arm/Group Title	Prophylaxis Arm, 7-day Regimen	Prophylaxis Arm, 10-day Regimen	Prophylaxis Arm, 14-day Regimen
Arm/Group Description:	Subjects received prophylactic rIX-FP on a weekly basis.	Subjects received prophylactic rIX-FP every 10 days.	Subjects received prophylactic rIX-FP every 14 days.
Overall Number of Participants Analyzed	38	7	21
Median (Inter-Quartile Range); Unit of Measure: bleeds/year/subject
	0.00; (0.00 to 0.00)	0.00; (0.00 to 0.00)	0.00; (0.00 to 1.00)

Adverse Events

Time Frame	For the duration of the study, up to 27.7 months.
Adverse Event Reporting Description	The Safety analysis population consisted of subjects who received at least 1 dose of rIX-FP during the study. Adverse Event (AE) data are treatment-emergent data unless otherwise noted. The total number of participants in the number affected by Other (non-serious) AEs, is the total number of participants experiencing at least one non-serious AE.
Arm/Group Title	Prophylaxis		On-demand
Arm/Group Description	Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.		Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
All-Cause Mortality
	Prophylaxis		On-demand
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Prophylaxis		On-demand
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/40 (2.50%)		2/23 (8.70%)
Musculoskeletal and connective tissue disorders
SYNOVITIS † 1	0/40 (0.00%)	0	1/23 (4.35%)	1
PAIN IN EXTREMITY † 1 [1]	1/40 (2.50%)	1	0/23 (0.00%)	0
MUSCLE HAEMORRHAGE † 1 [1]	1/40 (2.50%)	1	0/23 (0.00%)	0
Nervous system disorders
ACQUIRED EPILEPTIC APHASIA † 1	0/40 (0.00%)	0	1/23 (4.35%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1; [1] This serious adverse event was not treatment-emergent.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Prophylaxis		On-demand
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/40 (90.00%)		18/23 (78.26%)
Gastrointestinal disorders
DIARRHOEA † 1	2/40 (5.00%)	2	3/23 (13.04%)	4
TOOTHACHE † 1	4/40 (10.00%)	4	1/23 (4.35%)	1
Infections and infestations
NASOPHARYNGITIS † 1	10/40 (25.00%)	27	6/23 (26.09%)	11
INFLUENZA † 1	4/40 (10.00%)	7	3/23 (13.04%)	3
UPPER RESPIRATORY TRACT INFECTION † 1	5/40 (12.50%)	7	0/23 (0.00%)	0
BRONCHITIS † 1	4/40 (10.00%)	4	1/23 (4.35%)	1
PHARYNGITIS † 1	3/40 (7.50%)	3	2/23 (8.70%)	2
GASTROENTERITIS † 1	3/40 (7.50%)	4	0/23 (0.00%)	0
ACUTE TONSILLITIS † 1	0/40 (0.00%)	0	2/23 (8.70%)	2
Injury, poisoning and procedural complications
LIMB INJURY † 1	5/40 (12.50%)	5	1/23 (4.35%)	1
CONTUSION † 1	3/40 (7.50%)	5	1/23 (4.35%)	3
LACERATION † 1	1/40 (2.50%)	1	2/23 (8.70%)	2
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	9/40 (22.50%)	19	0/23 (0.00%)	0
BACK PAIN † 1	4/40 (10.00%)	5	2/23 (8.70%)	3
SYNOVITIS † 1	3/40 (7.50%)	6	0/23 (0.00%)	0
PAIN IN EXTREMITY † 1	3/40 (7.50%)	4	0/23 (0.00%)	0
JOINT SWELLING † 1	3/40 (7.50%)	3	0/23 (0.00%)	0
TENDONITIS † 1	3/40 (7.50%)	3	0/23 (0.00%)	0
Nervous system disorders
HEADACHE † 1	11/40 (27.50%)	26	4/23 (17.39%)	8
DIZZINESS † 1	4/40 (10.00%)	5	0/23 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
COUGH † 1	3/40 (7.50%)	3	0/23 (0.00%)	0
Skin and subcutaneous tissue disorders
ACNE † 1	3/40 (7.50%)	3	0/23 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: clinicaltrials@cslbehring.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Santagostino E, Martinowitz U, Lissitchkov T, Pan-Petesch B, Hanabusa H, Oldenburg J, Boggio L, Negrier C, Pabinger I, von Depka Prondzinski M, Altisent C, Castaman G, Yamamoto K, Alvarez-Roman MT, Voigt C, Blackman N, Jacobs I; PROLONG-9FP Investigators Study Group. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016 Apr 7;127(14):1761-9. doi: 10.1182/blood-2015-09-669234. Epub 2016 Jan 11.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT01496274
• Other Study ID Numbers: CSL654_3001; 2011-002415-28 ( EudraCT Number )
• First Submitted: December 19, 2011
• First Posted: December 21, 2011
• Results First Submitted: April 3, 2016
• Results First Posted: May 9, 2016
• Last Update Posted: May 9, 2016