Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01174446
First received: August 2, 2010
Last updated: September 20, 2013
Last verified: September 2013
Results First Received: September 20, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Hemophilia B
Interventions: Biological: BAX 326
Biological: BeneFIX

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment was conducted at 32 clinical sites in South America, Europe, Japan, and the United States

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

86 enrolled. 1 withdrew consent prior to randomization.

  • 31 were enrolled and randomized in Parts 1-3. Prior to receiving study drug: 3 discontinued by participant.
  • Part 2 an additional 54 were enrolled. Prior to receiving study drug: 3 discontinued by participant, 1 withdrew due to an AE, 2 screen failures, and 3 withdrew due to site closure.

Reporting Groups
  Description
PK (BAX326 Then BeneFIX) Then Prophylaxis Then PK BAX326 Only
  • Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 (75 ± 5 IU/kg) then BeneFIX (75 ± 5 IU/kg).
  • Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only
  • Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1
PK (BeneFIX Then BAX326) Then Prophylaxis Then PK BAX326 Only
  • Study Part 1: Pharmacokinetic (PK) Crossover with BeneFIX (75 ± 5 IU/kg) then BAX326 (75 ± 5 IU/kg).
  • Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only
  • Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1
Study Part 2 Only: BAX326 Prophylaxis -Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)
Study Part 2 Only: BAX326 On-Demand -Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)

Participant Flow for 3 periods

Period 1:   Part 1 -Pharmacokinetic Crossover
    PK (BAX326 Then BeneFIX) Then Prophylaxis Then PK BAX326 Only     PK (BeneFIX Then BAX326) Then Prophylaxis Then PK BAX326 Only     Study Part 2 Only: BAX326 Prophylaxis     Study Part 2 Only: BAX326 On-Demand  
STARTED     14     14     0     0  
COMPLETED     14 [1]   14     0     0  
NOT COMPLETED     0     0     0     0  
[1] BAX326 was mistakenly infused for second PK infusion (ie should have been BeneFIX) for 1 participant

Period 2:   Part 2 -BAX326 Prophylaxis and On-demand
    PK (BAX326 Then BeneFIX) Then Prophylaxis Then PK BAX326 Only     PK (BeneFIX Then BAX326) Then Prophylaxis Then PK BAX326 Only     Study Part 2 Only: BAX326 Prophylaxis     Study Part 2 Only: BAX326 On-Demand  
STARTED     14 [1]   14 [1]   31 [2]   14 [2]
COMPLETED     14     14     29     14  
NOT COMPLETED     0     0     2     0  
Withdrawal by Subject                 0                 0                 1                 0  
Physician Decision                 0                 0                 1                 0  
[1] In Study Part 2 all 14 participants received Prophylaxis
[2] This group only participated in Study Part 2

Period 3:   Part 3 -Pharmacokinetic BAX326 Only
    PK (BAX326 Then BeneFIX) Then Prophylaxis Then PK BAX326 Only     PK (BeneFIX Then BAX326) Then Prophylaxis Then PK BAX326 Only     Study Part 2 Only: BAX326 Prophylaxis     Study Part 2 Only: BAX326 On-Demand  
STARTED     14 [1]   14 [1]   0     0  
COMPLETED     13     13     0     0  
NOT COMPLETED     1     1     0     0  
Protocol Violation                 1                 0                 0                 0  
Required Emergency Surgery                 0                 1                 0                 0  
[1] Includes all participants who completed Part 1



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
All Study Participants Who Received Study Drug

BAX326 : -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX

  • Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only
  • Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1

Baseline Measures
    All Study Participants Who Received Study Drug  
Number of Participants  
[units: participants]
  73  
Age  
[units: years]
Mean ± Standard Deviation
  34.5  ± 12.2  
Gender  
[units: participants]
 
Female     0  
Male     73  
Region of Enrollment  
[units: participants]
 
United States     0  
Spain     1  
Ukraine     8  
Chile     4  
Russian Federation     12  
Colombia     5  
United Kingdom     2  
Czech Republic     2  
Argentina     2  
Brazil     1  
Poland     12  
Romania     8  
Bulgaria     10  
Germany     0  
Japan     5  
Sweden     1  



  Outcome Measures
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1.  Primary:   Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose   [ Time Frame: 72 hours ]

2.  Secondary:   Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)   [ Time Frame: 0-30 minutes before infusion up to 72 hours post-infusion ]

3.  Secondary:   Study Parts 1 and 3: Mean Residence Time (MRT)   [ Time Frame: 0-30 minutes before infusion up to 72 hours post-infusion ]

4.  Secondary:   Study Parts 1 and 3: Clearance (CL)   [ Time Frame: 0-30 minutes before infusion up to 72 hours post-infusion ]

5.  Secondary:   Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)   [ Time Frame: 0-30 minutes before infusion up to 1 hour post-infusion ]

6.  Secondary:   Incremental Recovery (IR) at 30 Minutes Over Time   [ Time Frame: 0-30 minutes before infusion and 30 minutes post-infusion ]

7.  Secondary:   Change in Incremental Recovery (IR) at 30 Minutes Over Time   [ Time Frame: 0-30 minutes before infusion and 30 minutes post-infusion ]

8.  Secondary:   Study Parts 1 and 3: Half Life (T 1/2)   [ Time Frame: 0-30 minutes before infusion up to 72 hours post-infusion ]

9.  Secondary:   Study Parts 1 and 3: Volume of Distribution at Steady State (Vss)   [ Time Frame: 0-30 minutes before infusion up to 72 hours post-infusion ]

10.  Secondary:   Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326   [ Time Frame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks) ]

11.  Secondary:   Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause   [ Time Frame: Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5) ]

12.  Secondary:   Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause   [ Time Frame: At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3) ]

13.  Secondary:   Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause   [ Time Frame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks) ]

14.  Secondary:   Consumption of BAX326 Per Event Per Participant   [ Time Frame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks) ]

15.  Secondary:   Consumption of BAX326 Per Participant: Median Number of Infusions Per Month   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks) ]

16.  Secondary:   Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks) ]

17.  Secondary:   Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

18.  Secondary:   Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability)   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

19.  Secondary:   Occurrence of Treatment Related Total Binding Antibodies   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

20.  Secondary:   Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

21.  Secondary:   Number of Participants Who Experienced Thrombotic Events   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

22.  Secondary:   Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

23.  Secondary:   Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

24.  Secondary:   Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

25.  Secondary:   Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

26.  Secondary:   Number of Adverse Events (AEs) After BAX326 Treatment   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks) ]

27.  Secondary:   Number of Participants With Adverse Events (AEs) After BAX326 Treatment   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks) ]

28.  Secondary:   EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

29.  Secondary:   EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

30.  Secondary:   General Pain Assessment Through a Visual Analog Scale (VAS)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

31.  Secondary:   Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

32.  Secondary:   SF-36: HRQoL 'Mental Health' (MH)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

33.  Secondary:   SF-36: HRQoL Physical Functioning' (PF)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

34.  Secondary:   SF-36: HRQoL Role-Physical (RP)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

35.  Secondary:   SF-36: HRQoL Role-Emotional   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

36.  Secondary:   SF-36: HRQoL Bodily Pain   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

37.  Secondary:   SF-36: HRQoL Mental Health   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

38.  Secondary:   SF-36: HRQoL Vitality   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

39.  Secondary:   SF-36: HRQoL Social Functioning   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

40.  Secondary:   SF-36: HRQoL General Health   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

41.  Secondary:   Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

42.  Secondary:   Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

43.  Secondary:   Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

44.  Secondary:   Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

45.  Secondary:   Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)   [ Time Frame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31) ]

46.  Secondary:   Health Resource Use - Number of Hospitalizations   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

47.  Secondary:   Health Resource Use - Total Days of Hospital Stay   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

48.  Secondary:   Health Resource Use - Emergency Room Visits   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

49.  Secondary:   Health Resource Use - Unscheduled Doctor's Office Visits   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]

50.  Secondary:   Health Resource Use - Days Lost From Work or School   [ Time Frame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Brigitt Abbuehl, MD, Global Medical Director, Hematology/Hemophilia
Organization: Baxter Innovations GmbH
e-mail: brigitt_abbuehl@baxter.com


Publications of Results:

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01174446     History of Changes
Other Study ID Numbers: 250901, 2009-016720-31
Study First Received: August 2, 2010
Results First Received: September 20, 2013
Last Updated: September 20, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública de Chile
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
Japan: Pharmaceuticals and Medical Devices Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: FSI Scientific Center of Expertise of Medical Application
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration