Clinical Trial Results:
An Open-Label, Single Dose Pharmacokinetic Study of Xyntha (Moroctocog Alfa [AF-CC], Recombinant Factor VIII) in Male Chinese Subjects with Hemophilia A
|
Summary
|
|
EudraCT number |
2015-003685-88 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
28 Aug 2015
|
|
Results information
|
|
Results version number |
v1 |
This version publication date |
11 Jun 2016
|
First version publication date |
11 Jun 2016
|
Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
B1831082
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Pfizer, Inc.
|
||
Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
|
||
Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 800-718-1021, ClinicalTrials.gov_Inquiries@Pfizer.com
|
||
Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 800-718-1021, ClinicalTrials.gov_Inquiries@Pfizer.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
28 Aug 2015
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
28 Aug 2015
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
28 Aug 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of the trial was to characterize single dose pharmacokinetic (PK) profile of Factor VIII (FVIII) activity after administration of Xyntha in male Chinese subjects with hemophilia A.
|
||
Protection of trial subjects |
This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jul 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
China: 13
|
||
Worldwide total number of subjects |
13
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
3
|
||
Adolescents (12-17 years) |
5
|
||
Adults (18-64 years) |
5
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
- | ||||||
|
Pre-assignment
|
|||||||
Screening details |
This study enrolled Chinese male subjects who were age 6 years or older with severe hemophilia A (FVIII activity <1%) previously treated with >150 exposure days to any FVIII-containing product. | ||||||
|
Period 1
|
|||||||
Period 1 title |
Overall Study (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
|
||||||
Blinding used |
Not blinded | ||||||
|
Arms
|
|||||||
|
Arm title
|
Xyntha 50 IU/kg | ||||||
Arm description |
Subjects were administered a single dose of recombinant antihemophilic factor (Xyntha) at approximately 50 international units per kilogram (IU/kg) infused intravenously (IV) over 10 minutes (actual dose received ranged from 42.55 IU/kg to 60.00 IU/kg). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
moroctocog alfa, recombinant FVIII
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Infusion
|
||||||
Routes of administration |
Intravenous use
|
||||||
Dosage and administration details |
single dose 50 IU/kg by IV infusion
|
||||||
|
|||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Xyntha 50 IU/kg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered a single dose of recombinant antihemophilic factor (Xyntha) at approximately 50 international units per kilogram (IU/kg) infused intravenously (IV) over 10 minutes (actual dose received ranged from 42.55 IU/kg to 60.00 IU/kg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Xyntha 50 IU/kg
|
||
Reporting group description |
Subjects were administered a single dose of recombinant antihemophilic factor (Xyntha) at approximately 50 international units per kilogram (IU/kg) infused intravenously (IV) over 10 minutes (actual dose received ranged from 42.55 IU/kg to 60.00 IU/kg). | ||
|
|||||||||
End point title |
Maximum Plasma FVIII Activity (Cmax) [1] | ||||||||
End point description |
The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Area Under the Plasma FVIII Activity-Time Profile from Time 0 to Time of the Last Quantifiable Concentration (AUClast) [2] | ||||||||
End point description |
The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Area Under the Plasma FVIII Activity-Time Profile from Time 0 Extrapolated to Infinite Time (AUCinf) [3] | ||||||||
End point description |
The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to Reach Maximum Observed Plasma Concentration (Tmax) [4] | ||||||||
End point description |
The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Clearance (CL) [5] | ||||||||
End point description |
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| Notes [5] - 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Volume of Distribution at Steady-State (Vss) [6] | ||||||||
End point description |
Volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the volume of distribution at steady-state. The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| Notes [6] - 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Terminal Phase Rate Constant (Kel) [7] | ||||||||
End point description |
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| Notes [7] - 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Terminal Elimination Half-Life (t1/2) [8] | ||||||||
End point description |
Terminal half-life is the time measured for the plasma concentration to decrease by one half. The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| Notes [8] - 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Mean Residence Time (MRT) [9] | ||||||||
End point description |
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method. The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| Notes [9] - 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Incremental Recovery (INCREC) [10] | ||||||||
End point description |
Incremental recovery is the increase in circulating FVIII activity for every IU of Xyntha administered per kilogram of body weight. The PK parameter analysis population is defined as all subjects enrolled and treated who have at least 1 of the PK parameters of primary interest reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
|
||||||||
| Notes [10] - 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: No statistical analysis was planned for this primary endpoint. No formal statistical inference or statistical modeling was to be performed. All PK parameters were summarized descriptively. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Number of Subjects with Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | ||||||||||
End point description |
An AE was any untoward medical occurrence in a subject who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs. The safety analysis population included all subjects who received at least 1 dose of study drug.
|
||||||||||
End point type |
Other pre-specified
|
||||||||||
End point timeframe |
Baseline up to Day 28
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||
End point title |
Number of Subjects with Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | ||||||||||||||
End point description |
The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count and morphology, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine drug screening, FVIII inhibitor assay, FVIII activity, prothrombin time [PT], activated partial thromboplastin time [APTT], anti-human immunodeficiency virus [HIV] 1, hepatitis C virus antibody [HCVAb], HAVAb, HBsAg, HBsAb, HBcAb). Only parameters which met abnormality criteria are reported.
|
||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||
End point timeframe |
Baseline up to Day 4
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Number of Subjects with Potentially Clinically Significant Vital Signs Findings | ||||||||||||||||||||||||
End point description |
Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <50 beats per minute (bpm), >=30 bpm increase from baseline, or >25 bpm decrease from baseline; systolic blood pressure (SBP) <90 milliliters of mercury (mmHg), >=30 mmHg increase from baseline, or >=30 mmHg decrease from baseline; diastolic blood pressure (DBP) <50 mmHg, >=20 mmHg increase from baseline, or >=20 mmHg decrease from baseline. The safety analysis population included all subjects who received at least 1 dose of study drug.
|
||||||||||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||||||||||
End point timeframe |
Baseline up to Day 4
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||
End point title |
Number of Subjects with Positive FVIII Inhibitor Activity at Day 4 | ||||||
End point description |
As with all FVIII products, subjects using Xyntha were monitored for the development of FVIII inhibitors. Values >= 0.6 Bethesda Unit (BU) per mL were considered positive results. The safety analysis population included all subjects who received at least 1 dose of study drug.
|
||||||
End point type |
Other pre-specified
|
||||||
End point timeframe |
Day 4
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to Day 28
|
||||||||||||||||||||||
Adverse event reporting additional description |
The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another, or 1 subject may have experienced both an AE and SAE during the study. All treated subjects were included in the analysis.
|
||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||
Dictionary version |
18.1
|
||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||
Reporting group title |
Xyntha 50 IU/kg
|
||||||||||||||||||||||
Reporting group description |
Subjects were administered a single dose of recombinant antihemophilic factor (Xyntha) at approximately 50 IU/kg infused IV over 10 minutes (actual dose received by subjects ranged from 42.55 IU/kg to 60.00 IU/kg). | ||||||||||||||||||||||
|
|||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||
|
|||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
