Clinical Trial Results:
Phase 4, Multicenter, Prospective, Interventional, Post-Marketing Study in Hemophilia A Patients in India Receiving ADVATE as On-Demand or Prophylaxis Under Standard Clinical Practice
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Summary
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EudraCT number |
2022-004149-11 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
10 Feb 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Aug 2023
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First version publication date |
23 Aug 2023
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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 |
TAK-761-4009
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04985682 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Avenue, Lexington, United States, MA 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Feb 2023
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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 |
10 Feb 2023
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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 |
The main objective of this study is to assess the safety of ADVATE based on serious adverse events (SAEs) [including factor VIII (FVIII) inhibitors].
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Protection of trial subjects |
All study participants or legally authorised representative (in case of study participants <18 years of age) were required to read and sign an informed consent form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Jan 2022
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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 |
India: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
0
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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) |
14
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Adolescents (12-17 years) |
10
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Adults (18-64 years) |
26
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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 |
Participants took part in the study at 4 investigative sites in India from 14 January 2022 to 10 February 2023. | ||||||||||
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Pre-assignment
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Screening details |
Participants previously treated for hemophilia A who met eligibility criteria were enrolled to receive ADVATE according to a dosing regimen determined by the treating physician and in accordance with the national product label. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Hemophilia A Group | ||||||||||
Arm description |
Participants with hemophilia A were treated with ADVATE according to a regimen determined by the treating physician at the study site and in accordance with the national product label under standard clinical practice for 6.7 months. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
ADVATE
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Antihemophilic factor (AHF) activity expressed in international units (IU) per vial.
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Baseline characteristics reporting groups
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Reporting group title |
Hemophilia A Group
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Reporting group description |
Participants with hemophilia A were treated with ADVATE according to a regimen determined by the treating physician at the study site and in accordance with the national product label under standard clinical practice for 6.7 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Hemophilia A Group
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Reporting group description |
Participants with hemophilia A were treated with ADVATE according to a regimen determined by the treating physician at the study site and in accordance with the national product label under standard clinical practice for 6.7 months. | ||
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End point title |
Number of Participants With Serious Adverse Events (SAE) at Least Possibly Related to ADVATE [1] | ||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. An SAE was defined as any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of present hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was a medically important event. Number of participants with SAEs (including FVIII inhibitor formation) that were at least possibly related to ADVATE were reported. Safety Analysis Set (SAS) included all participants who received ADVATE at any time during the study.
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End point type |
Primary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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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: Only descriptive statistics were planned to be analysed for this endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Non-serious Adverse Events (AEs) at Least Possibly Related to ADVATE | ||||||
End point description |
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. Number of participants with non-serious AEs that were at least possibly related to ADVATE were reported. SAS included all participants who received ADVATE at any time during the study.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | ||||||
End point description |
Clinical laboratory parameters included hematology, clinical chemistry, viral serology, factor VIII (FVIII) antigen, FVIII activity, incremental recovery, and FVIII inhibitor. Clinical significance was judged as per Investigator’s assessment. SAS included all participants who received ADVATE at any time during the study.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Total Annualized Bleeding Rate (ABR) With Prophylactic Treatment of ADVATE | ||||||||||
End point description |
ABR was defined as number of bleeding episodes during the study period divided by total number of study period days multiplied by 365.25. The mean ABR and standard error was estimated using a generalized linear model (GLM). The total ABR is reported in this outcome measure. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||||
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End point title |
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed | ||||||||||||||||
End point description |
ABR was defined as number of bleeding episodes during the study period divided by total number of study period days multiplied by 365.25. The mean ABR and standard error were estimated using a GLM. The ABR by bleed sites (example, joint, soft tissue, muscle, other [mouth, gums or nose] are reported in this outcome measure. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
ABR With Prophylactic Treatment of ADVATE Categorized Based on Type of Bleed | ||||||||||||||
End point description |
ABR was defined as number of bleeding episodes during the study period divided by total number of study period days multiplied by 365.25. The mean ABR and standard error were estimated using a GLM. The ABR by bleed cause (example, spontaneous, injury, and unknown) are reported in this outcome measure. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Total Number of ADVATE Infusions Required During Prophylactic Treatment | ||||||||
End point description |
EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Average Number of ADVATE Infusions Required per Week During Prophylactic Treatment | ||||||||||
End point description |
EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Average Number of ADVATE Infusions Required per Month During Prophylactic Treatment of Bleeding Episode | ||||||||
End point description |
EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Total Body Mass Adjusted Consumption of ADVATE During Prophylactic Treatment | ||||||||
End point description |
Body mass adjusted consumption international units per kilograms (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Average Body Mass Adjusted Consumption of ADVATE per Week During Prophylactic Treatment | ||||||||||
End point description |
Body mass adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Average Body Mass Adjusted Consumption of ADVATE per Month During Prophylactic Treatment | ||||||||
End point description |
Body mass adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes | ||||||||||||||
End point description |
Overall hemostatic efficacy for bleeding episodes treatment was rated on 4-point Likert scale as:excellent=full relief of pain,cessation of objective signs of bleeding after single infusion,no additional infusion is required for control of bleeding,administration of further infusion to maintain hemostasis would not affect scoring;good=definite pain relief and/or improvement in signs of bleeding after single infusion,possibly requires more than 2 infusions for complete resolution,administration of further infusion to maintain hemostasis would not affect scoring;moderate=probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion,required multiple infusions for complete resolution;none=no improvement of signs/symptoms/conditions worsen.EFAS=all participants for whom all inclusion and none of the exclusion criteria were met.Number of subjects analysed=participants with bleeds who required ADVATE infusion for management of bleeding episode.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of ADVATE Infusions Required to Achieve Resolution of Bleeding Episodes | ||||||||
End point description |
EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Number of subjects analysed are the number of participants with bleeds who required ADVATE infusion for management of the bleeding episode.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Total Body Mass Adjusted Consumption of ADVATE per Bleeding Episode | ||||||||
End point description |
Body mass adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion. EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Number of subjects analysed are the number of participants with bleeds who required ADVATE infusion for management of the bleeding episode.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) up to end of study (up to 12.9 months)
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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 |
Baseline (Day 0) up to end of study (up to 12.9 months)
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Adverse event reporting additional description |
SAS included all participants who received ADVATE at any time during the study.
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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 |
25.0
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Reporting groups
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Reporting group title |
Hemophilia A Group
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Reporting group description |
Participants with hemophilia A were treated with ADVATE according to a regimen determined by the treating physician at the study site and in accordance with the national product label under standard clinical practice for 6.7 months. | ||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
