Clinical Trial Results:
Pharmacokinetics of WILATE® and Haemate® P in von Willebrand type 3 patients - a prospective, randomised, controlled, open-labelled, 2-arm cross-over study.
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Summary
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EudraCT number |
2008-001910-25 |
Trial protocol |
SK |
Global end of trial date |
14 Jan 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jan 2017
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First version publication date |
06 Jan 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
WIL-21
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Octapharma AG
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Sponsor organisation address |
Seidenstraße 2, Lachen, Switzerland, CH-8853
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Public contact |
Bruce Schwartz, Octapharma USA, Inc.
, +1 (201)604-1112, bruce.schwartz@octapharma.com
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Scientific contact |
Bruce Schwartz, Octapharma USA, Inc.
, +1 (201)604-1112, bruce.schwartz@octapharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Jun 2012
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jan 2010
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine the half-life of WILATE® in terms of the ristocetin cofactor activity (VWF:RCo), the FVIII coagulant activity (FVIII:C), the VWF antigen (VWF:Ag), and collagen binding activity (VWF:CB) of WILATE® and to compare these parameters with those for Haemate® P.
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Protection of trial subjects |
This trial was conducted in accordance to the principles of GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the declaration of Helsinki. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and safety factors associated with the investigational medicinal product. Throughout the study safety was assessed, such as occurrence of AEs, labvalues, vital signs and physical examinations.
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Background therapy |
NA | ||
Evidence for comparator |
Haemate® P (CSL Behring GmbH): Vials of approximately 600 IU VWF:RCo. A dose of at least 40 IU VWF:RCo/kg body weight was given intravenously by bolus administration. One batch of Haemate® P was used (20566911G). Haemate® P is a commercially available product. Each vial of Haemate® P had a labelled (nominal) potency of 600 IU of VWF:RCo and 250 IU FVIII:C (VWF:RCo/FVIII:C ratio of ~2.4:1) that was to be reconstituted in 5 mL water for injections. | ||
Actual start date of recruitment |
28 Aug 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Slovakia: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
7
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Defined inherited VWD type 3, Male or female patients ≥ 12 years of age with a body weight ≥ 32 kg and ≤ 125 kg, Negative for Hepatitis B surface antigen (HBsAg), Any human immunodeficiency virus (HIV)-positive patients had to have a baseline CD4+ cell count of > 200/mm3, and a platelet count of > 100,000/dL, freely given informed consent. | |||||||||
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Pre-assignment
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Screening details |
Patients were randomly assigned to receive either WILATE® or Haemate® P in Period 1. After a washout period of at least 7 days, but not more than 4 weeks, patients were switched to the other study drug for Period 2. Randomisation took place before study drug administration and patient satisied all of the inclusion criteria for Period 1, Visit 2. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Period 1 | |||||||||
Arm description |
Patients were randomly assigned to receive either WILATE® or Haemate® P in Period 1, and then switched to the other study drug for Period 2. Randomisation took place before study drug administration, i.e., when the patient satisfied all of the entry criteria required for inclusion in Period 1 Visit 2. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
VWF/FVIII containing human coagulation concentrate
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Investigational medicinal product code |
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Other name |
Wilate(R), plasma derived VWF:FVIII concentrate
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A single dose of at least 40 IU VWF:RCo/kg body weight of WILATE® (using the labelled potency) was administered intravenously by bolus administration in each study period. The dose of WILATE® selected for the study is in line with that previously used in clinical studies. A single, bolus, intravenous dose of approximately 50 IU VWF:RCo/kg body weight has been previously administered to patients with VWD (studies TMAE-105, TMAE-109 TMAE-104 and TMAE-106) and a single, intravenous, bolus dose of at least 40 IU VWF:RCo/kg body weight of WILATE® was administered in study WIL-12.
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Investigational medicinal product name |
VWF/FVIII containing human coagulation concentrate
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Investigational medicinal product code |
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Other name |
Haemate(R)P
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A single dose of at least 40 IU VWF:RCo/kg body weight of Haemate® P (using the labelled potency) was administered intravenously by bolus administration in each study period.
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Arm title
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Period 2 | |||||||||
Arm description |
Patients were randomly assigned to receive either WILATE® or Haemate® P in Period 1, and then switched to the other study drug for Period 2. Randomisation took place before study drug administration, i.e., when the patient satisfied all of the entry criteria required for inclusion in Period 1 Visit 2. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
VWF/FVIII containing human coagulation concentrate
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Investigational medicinal product code |
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Other name |
Wilate(R), plasma derived VWF:FVIII concentrate
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A single dose of at least 40 IU VWF:RCo/kg body weight of WILATE® (using the labelled potency) was administered intravenously by bolus administration in each study period. The dose of WILATE® selected for the study is in line with that previously used in clinical studies. A single, bolus, intravenous dose of approximately 50
IU VWF:RCo/kg body weight has been previously administered to patients with VWD (studies TMAE-105, TMAE-109 TMAE-104 and TMAE-106) and a single, intravenous,
bolus dose of at least 40 IU VWF:RCo/kg body weight of WILATE® was administered in study WIL-12.
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Investigational medicinal product name |
VWF/FVIII containing human coagulation concentrate
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Investigational medicinal product code |
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Other name |
Haemate(R)P
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A single dose of at least 40 IU VWF:RCo/kg body weight of WILATE® or Haemate® P (using the labelled potency) was administered intravenously by bolus administration in each study period.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Period 1
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Reporting group description |
Patients were randomly assigned to receive either WILATE® or Haemate® P in Period 1, and then switched to the other study drug for Period 2. Randomisation took place before study drug administration, i.e., when the patient satisfied all of the entry criteria required for inclusion in Period 1 Visit 2. | ||
Reporting group title |
Period 2
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Reporting group description |
Patients were randomly assigned to receive either WILATE® or Haemate® P in Period 1, and then switched to the other study drug for Period 2. Randomisation took place before study drug administration, i.e., when the patient satisfied all of the entry criteria required for inclusion in Period 1 Visit 2. | ||
Subject analysis set title |
PK-evaluable population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The PK-evaluable population consisted of all patients in the ITT/safety population who had concentration data at baseline (before the injection) and at least four post-infusion time points for both study periods. Of the 9 patients originally enrolled, 1 was excluded from the PK-evaluable set as she was suspected not to be a VWD type 3 patient.
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End point title |
VWF:RCo - Terminal half-lives (h) in the PK-evaluable population [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
end of the study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Confidence interval of VWF:RCo of t1/2 in the PK-evaluable population: Estimated ratio of geometric means of Wilate(R) vs Haemate(R)P (%): 102.3 Two-sided 90% CI (%): 85.5 - 122.5 p-value: 0.8161 |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
VWF:Ag - Terminal half-lives (h) in the PK-evaluable population [2] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Confidence interval of VWF:RCo of t1/2 in the PK-evaluable population: Estimated ratio of geometric means of Wilate(R) vs Haemate(R)P (%): 93.9 Two-sided 90% CI (%): 81.0 - 109.0 p-value: 0.4504 |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
VWF:CB - Terminal half-lives (h) in the PK-evaluable population [3] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Confidence interval of VWF:RCo of t1/2 in the PK-evaluable population: Estimated ratio of geometric means of Wilate(R) vs Haemate(R)P (%): 102.7 Two-sided 90% CI (%): 86.1 - 122.5 p-value: 0.7813 |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
FVIII:C - Terminal half-lives (h) in the PK-evaluable population [4] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Confidence interval of VWF:RCo of t1/2 in the PK-evaluable population: Estimated ratio of geometric means of Wilate(R) vs Haemate(R)P (%): 101.7 Two-sided 90% CI (%): 83.5 - 124.0 p-value: 0.8712 |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were assessed throughout the whole study.
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Adverse event reporting additional description |
All SAEs, whether suspected to be related to study treatment or not, are reported by telephone, fax or e-mail immediately to the responsible Clinical Project Manager, study monitor, or to the responsible local CRO.
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Assessment type |
Systematic | ||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||
Dictionary version |
13.0
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Reporting groups
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Reporting group title |
Overall Trail
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Reporting group description |
- | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Oct 2008 |
Amendment 1
• Changed to a single-centre study design |
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03 Mar 2009 |
Amendment 2
• Addition of VWF multimer analysis
• Inclusion of an additional 3 patients for a total of 9 patients
• Changed to a multi-centre study design
• Inclusion of the 900 IU FVIII batch size of WILATE® as an investigational product
• Specification that noncompartmental PK analysis will be performed
• Calculation of PK parameters using actual potency of drug |
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21 Jul 2009 |
Amendment 3
• Changed to a single-centre study design |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
