Hemophilia ANCT04876365
A Study in Children, Teenagers and Adults With Severe Hemophilia A Who Switched From Other Factor VIII Treatments to Adynovate
An observational study of Hemophilia A, run by Takeda at 1 site in Canada.
Trial summary
The main aims of the study are to assess the safety profile of Adynovate as well as how well people respond to the preventive treatment with Adynovate. This study is about reviewing and collecting data of the participants before and after the switch to Adynovate that are already available. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Non-Interventional
- How many people
- 153 participants
- Where
- 1 siteCanada
- Study dates
- 30 Nov 2021to 28 Feb 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study population will comprise of participants of all ages receiving regular prophylactic treatment with Adynovate at a Canadian Hemophilia Treatment Center and registered in CBDR (Canadian Bleeding Registry).
Who may be able to join
- Participants with severe hemophilia A.
- All age groups (less than [<] 12 and greater than [>] 12 years of age).
- Participant with greater than equal to (>=) 150 documented exposure days (EDs).
- Treated with Adynovate:
- Having a PK analysis done/data available for post-hoc modeling
- Having recorded clinical outcomes analysis: for > 6 months
- Treated with a SHL/EHL-FVIII product for at least six months before switching to Adynovate
- To qualify for the secondary objective participants will need to have a WAPPS study performed on Adynovate and on the SHL/EHL-FVIII they were treated before switching.
Who cannot join
- Any participant who meets any of the following criteria will not qualify for entry into the study:
- Participants with only on-demand Factor VIII (FVIII) use.
- Current presence of FVIII inhibitory antibodies. (Participants with a history of inhibitors, if any, will be considered for a sensitivity analysis).
- Diagnosis of other inherited or acquired hemostatic defect other than hemophilia A.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Hamilton-Niagara Regional Hemophilia Treatment Centre
Hamilton, Ontario, L8N 3Z5
About this study
Official title: Real-World Effectiveness of PEGylated, Recombinant Antihemophilic Factor (Adynovate) Prophylaxis in Patients With Hemophilia A in Canada: A Retrospective, Intra-patient Comparison With a Before-After Design
The main aims of the study are to assess the safety profile of Adynovate as well as how well people respond to the preventive treatment with Adynovate.
This study is about reviewing and collecting data of the participants before and after the switch to Adynovate that are already available. No new information will be collected during this study. The total time for data collection in the study will be approximately 72 months (36 months before and 36 months after switching to Adynovate). Participants will not receive Adynovate as part of this study.
As participants are not treated in this study, they do not need to visit their doctor in addition to their normal visits.
- Conditions
- Hemophilia A
- Being tested
- Non-Interventional
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-InterventionalOther
This is a Non-Interventional Study.
| Study group | Role | What they receive |
|---|---|---|
| All Participants | All participants diagnosed with severe hemophilia A previous received prophylaxis regimen for Standard Half-life/Extended Half-life Factor VIII (SHL/EHL-FVIII) products will be compared to after the participants switched to regular prophylaxis with Adynovate with at least 6 months follow up. Receives: Other: Non-Interventional |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Time Spent With Factor Levels Above 0.01 IU/ml
Percentage of time spent with factor levels above 0.01 (International units per milliliter [IU/ml], is calculated as: time spent with factor levels above 0.01 IU/ml/ total time in the study. The calculation will be performed by simulating, based on the infusions recorded in the treatment diaries and the individual PK profiles, all the times intervals between each infusion and the time at which the concentration of 0.01 IU/mL is reached, and the time between reaching the 0.01 IU/mL and the subsequent infusion.
Measured: approximately 72 months
Number of Participants With Adverse Events (AEs)
An AEs is any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. Number of participants with AEs related to inhibitor development, thrombosis, death, infection, cancer and other will be reported.
Measured: approximately 72 months
Secondary outcomes (16)
Percentage of Time Spent With Factor Levels Above 0.03 IU/ml
Percentage of time spent with factor levels above 0.03 IU/ml, is calculated as: time spent with factor levels above 0.03 IU/ml/ total time in the study. The calculation will be performed by simulating, based on the infusions recorded in the treatment diaries and the individual.
Measured: approximately 72 months
Percentage of Time Spent With Factor Levels Above 0.05 IU/ml
Percentage of time spent with factor levels above 0.05 IU/ml, is calculated as: time spent with factor levels above 0.05 IU/ml/ total time in the study. The calculation will be performed by simulating, based on the infusions recorded in the treatment diaries and the individual.
Measured: approximately 72 months
Terminal Half-life of Adynovate
Terminal half-life will be estimated based on the individual Web-Accessible Population Pharmacokinetic Hemophilia Service (WAPPS) PK profile.
Measured: approximately 72 months
Clearance (Cl) of Adynovate
Cl will be estimated based on the individual WAPPS PK profile.
Measured: approximately 72 months
Maximum Observed Drug Concentration (Cmax) of Adynovate
Cmax is as estimated based on the individual WAPPS PK profile.
Measured: approximately 72 months
Area Under the Curve (AUC) of Adynovate
AUC will be estimated based on the individual WAPPS PK profile.
Measured: approximately 72 months
Annualized Total Factor Consumption
The total factor consumption will be measured on the infusion log, annualized and adjusted per body weight. Annualized FVIII concentrate consumption, adjusted per body weight, will be calculated as: total amount infused IU/ Weight (kilograms)*12/months of observation.
Measured: approximately 72 months
Annualized Total Factor Consumption for Bleeds
The total factor consumption for bleeds will be measured on the infusion log, annualized and adjusted per body weight. Annualized FVIII concentrate consumption, adjusted per body weight, will be calculated as: total amount infused IU for bleeds/ Weight (kilograms)*12/months of observation.
Measured: approximately 72 months
Estimated Factor Consumption
Estimated factor consumption, based on the prescribed treatment regimen, annualized and adjusted per body weight, is calculated as: total amount prescribed (IU)/week / Weight (kilograms)*52/weeks of observation.
Measured: approximately 72 months
Theoretical Factor Consumption
Theoretical factor consumption, estimated based on the amount required to obtain specified factor level troughs (0.03 IU/mL, 0.10 IU/mL), annualized and adjusted per body weight, will be calculated as: estimated amount prescribed IU/week / Weight (kilograms)*52/weeks of observation.
Measured: approximately 72 months
Annualized Bleeding Rate (ABR)
ABR will be calculated as: number of bleeds*12/months of observation.
Measured: approximately 72 months
Annualized Spontaneous Bleeding Rate (AsBR),
AsBR will be calculated as: number of spontaneous bleeds*12/months of observation. A bleed is defined as spontaneous if it is not related to injury/trauma.
Measured: approximately 72 months
Annualized Joint Bleeding Rate (AjBR)
AjBR will be calculated as: number of joint bleeds*12/months of observation. An acute joint bleed include some or all of the following: 'aura', pain, swelling, warmth of the skin over the joint, decreased range of motion and difficulty in using the limb compared with baseline or loss of function.
Measured: approximately 72 months
Hemophilia Joint Health Score (HJHS)- Total Score
HJHS will be assessed based on the following components of the elbow, knee, and ankle joints: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength, together with an assessment of the global gait. The HJHS is a validated 11-item scoring tool based on radiologic and clinical evaluation, sensitive to detect early signs and minor changes. HJHS ranges from 0 to 124. Higher values in the HJHS represent worse situation for the participant.
Measured: approximately 72 months
Health-Related Quality of Life (HRQoL) Assessed by Patient-reported Outcome Burdens and Experiences (PROBE) Questionnaire
The PROBE questionnaire is a tool for the assessment of patient-reported outcome, burdens and experiences. Until now, it has been used in persons living with hemophilia (PWH) and healthy controls. PROBE questionnaire consists of four major sections: demographic data, general health problems, hemophilia-related health problems and health-related quality of life. Scores range from 0-1, with a higher value indicating better health status.
Measured: approximately 72 months
HRQoL Assessed by EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L)
The EQ-5D-5L descriptive system assesses health in five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which has five levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems/unable to). This part of the EQ-5D questionnaire provides a descriptive profile that can be used to generate a health state profile. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The second part of the questionnaire consists of a visual analogue scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health).
Measured: approximately 72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start30 Nov 2021
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04876365
- Sponsor's protocol ID
- TAK-660-4004
- Other IDs
- MACS-2020-061601
- Status last verified
- Jul 2023
- First submitted
- 5 May 2021
- Last updated
- 24 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-World Effectiveness of PEGylated, Recombinant Antihemophilic Factor (Adynovate) Prophylaxis in Patients With Hemophilia A in Canada: A Retrospective, Intra-patient Comparison With a Before-After Design
- ClinicalTrials.gov ID
- NCT04876365
- Acronym / sponsor ID
- TAK-660-4004
- Conditions
- Hemophilia A
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 6 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main aims of the study are to assess the safety profile of Adynovate as well as how well people respond to the preventive treatment with Adynovate.
This study is about reviewing and collecting data of the participants before and after the switch to Adynovate that are already available. No new information will be collected during this study. The total time for data collection in the study will be approximately 72 months (36 months before and 36 months after switching to Adynovate). Participants will not receive Adynovate as part of this study.
As participants are not treated in this study, they do not need to visit their doctor in addition to their normal visits.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Participants | – | Other: Non-InterventionalAll participants diagnosed with severe hemophilia A previous received prophylaxis regimen for Standard Half-life/Extended Half-life Factor VIII (SHL/EHL-FVIII) products will be compared to after the participants switched to regular prophylaxis with Adynovate with at least 6 months follow up. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study population will comprise of participants of all ages receiving regular prophylactic treatment with Adynovate at a Canadian Hemophilia Treatment Center and registered in CBDR (Canadian Bleeding Registry).
Key inclusion criteria (8 listed)
- Participants with severe hemophilia A.
- All age groups (less than [<] 12 and greater than [>] 12 years of age).
- Participant with greater than equal to (>=) 150 documented exposure days (EDs).
- Treated with Adynovate:
- Treated with a SHL/EHL-FVIII product for at least six months before switching to Adynovate
Key exclusion criteria (4 listed)
- Any participant who meets any of the following criteria will not qualify for entry into the study:
- Participants with only on-demand Factor VIII (FVIII) use.
- Current presence of FVIII inhibitory antibodies. (Participants with a history of inhibitors, if any, will be considered for a sensitivity analysis).
- Diagnosis of other inherited or acquired hemostatic defect other than hemophilia A.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-InterventionalThis is a Non-Interventional Study. | Other | All Participants |
Primary outcome
Percentage of Time Spent With Factor Levels Above 0.01 IU/ml
Time frame: approximately 72 months
Percentage of time spent with factor levels above 0.01 (International units per milliliter [IU/ml], is calculated as: time spent with factor levels above 0.01 IU/ml/ total time in the study. The calculation will be performed by simulating, based on the infusions recorded in the treatment diaries and the individual PK profiles, all the times intervals between each infusion and the time at which the concentration of 0.01 IU/mL is reached, and the time between reaching the 0.01 IU/mL and the subsequent infusion.
Number of Participants With Adverse Events (AEs)
Time frame: approximately 72 months
An AEs is any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. Number of participants with AEs related to inhibitor development, thrombosis, death, infection, cancer and other will be reported.
16 secondary outcomes
Percentage of Time Spent With Factor Levels Above 0.03 IU/ml
Time frame: approximately 72 months
Percentage of Time Spent With Factor Levels Above 0.05 IU/ml
Time frame: approximately 72 months
Terminal Half-life of Adynovate
Time frame: approximately 72 months
Clearance (Cl) of Adynovate
Time frame: approximately 72 months
Maximum Observed Drug Concentration (Cmax) of Adynovate
Time frame: approximately 72 months
Area Under the Curve (AUC) of Adynovate
Time frame: approximately 72 months
Annualized Total Factor Consumption
Time frame: approximately 72 months
Annualized Total Factor Consumption for Bleeds
Time frame: approximately 72 months
Estimated Factor Consumption
Time frame: approximately 72 months
Theoretical Factor Consumption
Time frame: approximately 72 months
Annualized Bleeding Rate (ABR)
Time frame: approximately 72 months
Annualized Spontaneous Bleeding Rate (AsBR),
Time frame: approximately 72 months
Annualized Joint Bleeding Rate (AjBR)
Time frame: approximately 72 months
Hemophilia Joint Health Score (HJHS)- Total Score
Time frame: approximately 72 months
Health-Related Quality of Life (HRQoL) Assessed by Patient-reported Outcome Burdens and Experiences (PROBE) Questionnaire
Time frame: approximately 72 months
HRQoL Assessed by EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L)
Time frame: approximately 72 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2023.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophilia A, run by Takeda at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Time Spent With Factor Levels Above 0.01 IU/ml (time frame: approximately 72 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2023.