Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia A

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Octapharma
ClinicalTrials.gov Identifier:
NCT00989196
First received: September 30, 2009
Last updated: December 16, 2013
Last verified: December 2013
Results First Received: March 1, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hemophilia A
Interventions: Biological: Human-cl rhFVIII
Biological: Kogenate FS

  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
The study was conducted at 6 centers in the USA, 2 centers in Germany and 1 center in Bulgaria. The first patient was included on May 27, 2010 and the last patient finished the study on September 18, 2012

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The patients started the study with a PK period. The PK period had a cross-over design (Kogenate vs Human cl rhFVIII) and subjects received either Kogenate first and Human cl rhFVIII second or vice versa. Once the PK measure had been done, the patient started the treatment period with Human cl rhFVIII only.

Reporting Groups
  Description
Human c1 rhFVIII First Crossover, Then Treatment Participants were randomized to receive Human-cl rhFVIII (50 IU/kg bodyweight) first, then Kogenate FS (50 IU/kg bodyweight)second in the Crossover period. In the Treatment Period, participants received Human-cl rhFVIII (50 IU/kg bodyweight)
Kogenate First Crossover, Then Treatment Participants were randomized to receive Kogenate (50 IU/kg) first (14 days), then Human-cl rhFVIII (50 IU/kg bodyweight) second (14 days) in the Crossover period. In the Treatment Period, participants received Human-cl rhFVIII (50 IU/kg bodyweight)

Participant Flow for 2 periods

Period 1:   PK Crossover Period
    Human c1 rhFVIII First Crossover, Then Treatment     Kogenate First Crossover, Then Treatment  
STARTED     10     12  
COMPLETED     10     12  
NOT COMPLETED     0     0  

Period 2:   Treatment Period
    Human c1 rhFVIII First Crossover, Then Treatment     Kogenate First Crossover, Then Treatment  
STARTED     10     12  
COMPLETED     9     12  
NOT COMPLETED     1     0  
Lost to Follow-up                 1                 0  



  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
Human cl rhFVIII Human-cl rhFVIII and Kogenate in cross-over design:50 IU/kg for PK dose

Baseline Measures
    Human cl rhFVIII  
Number of Participants  
[units: participants]
  22  
Age  
[units: participants]
 
<=18 years     2  
Between 18 and 65 years     19  
>=65 years     1  
Age  
[units: years]
Mean ± Standard Deviation
  39.6  ± 14.06  
Gender  
[units: participants]
 
Female     0  
Male     22  
Region of Enrollment  
[units: participants]
 
United States     10  
Bulgaria     6  
Germany     6  



  Outcome Measures
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1.  Primary:   The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

2.  Secondary:   Pharmacokinetic Parameter: Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

3.  Secondary:   Maximum Plasma Concentration (Cmax) for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

4.  Secondary:   Time to Reach Maximum Plasma Concentration (Tmax) for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

5.  Secondary:   Mean Residence Time (MRT) for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

6.  Secondary:   Volume of Distribution at Steady State (Vss) for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

7.  Secondary:   Clearance (CL) for Human-cl rhFVIII Compared to Kogenate FS   [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ]

8.  Secondary:   Efficacy of On-demand Treatment of Bleeding Episodes   [ Time Frame: From 1st treatment after PK cycle 2 until study end. ]

9.  Secondary:   Immunogenicity (Number of Patients That Developed an Inhibitor During the Course of the Study)   [ Time Frame: study entry, then immediately before both PK cycles, in the 48 hour sample of both PK cycles, after 10 to 15 EDs with human-cl rhFVIII, at the 3-month visit (± 2 weeks), then every 3 months (± 2 weeks) until study completion, and after >50 EDs (except for ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Dr. Sigurd Knaub
Organization: Octapharma AG
phone: +41 554512141
e-mail: sigurd.knaub@octapharma.com


No publications provided


Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT00989196     History of Changes
Other Study ID Numbers: GENA-01
Study First Received: September 30, 2009
Results First Received: March 1, 2013
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
Bulgaria: Bulgarian Drug Agency