Hemophilia APMCHNCT03615053
Personalized Medicine for Canadians With Hemophilia
A study testing Implementation of WAPPS-Hemo personalized dosing regimen in people with Hemophilia A and Hemophilia B, run by McMaster University at 7 sites in Canada.
Trial summary
Performing an individual pharmacokinetic (PK) estimate is only the first step in implementing tailored prophylaxis, which requires using the PK profile information to design a personalized treatment regimen matching the treatment needs of individual patients. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Hemophilia A, Hemophilia B
- What is being tested?
- Implementation of WAPPS-Hemo personalized dosing regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 7 sitesCanada
- Study dates
- 24 Jul 2019to 30 Sep 2023
- Phase
- Interventional
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- individuals with severe congenital hemophilia A and B;
- on continuous factor prophylaxis;
- must be registered on CBDR (iCHIP in BC)
Who cannot join
- a history of explicit and documented previous treatment tailoring based on pharmacokinetic profiling;
- another congenital or acquired bleeding disorders other than Hemophilia A or B;
- active inhibitors (> 5 Bethesda units) or currently undergoing immune tolerance induction.
Trial locations and contacts
7 sites in 1 country.
Noella Noronha, BSc contact
7 sites in 1 country
Canada7 sites, 7 recruiting
- Recruiting
University of Calgary
Calgary, Alberta
Julia Hews-Girard, RN, julia.hewsgirard@albertahealthservices.ca
Adrienne Lee, MD
- Recruiting
University of Alberta
Edmonton, Alberta
Vicki Voong, RN, vvoong@ualberta.ca
Linda Sun, MD
- Recruiting
McMaster University
Hamilton, Ontario, L8S4B2
Noella Noronha, BSc, noronn@mcmaster.ca
Alfonso Iorio, MD
- Recruiting
McMaster University
Hamilton, Ontario
Theresa Almonte, almontet@hhsc.ca
David Chan, MD
- Recruiting
Queen's University
Kingston, Ontario
Julie Grabell, MD, grabell@queensu.ca
Paula James, MD
- Not yet recruiting
University of British Columbia
Vancouver, British Columbia
Shannon Jackson, MD
- Recruiting
University of Manitoba
Winnipeg, Manitoba
Ming Yang, MYang@providencehealth.bc.ca
Jayson Stoffman, MD
About this study
Official title: Personalized Medicine for Canadians With Hemophilia: a Pragmatic Evaluation of the Web-Accessible Population Pharmacokinetics Service- Hemophilia (WAPPS-Hemo) Tailored Dosing.
Performing an individual pharmacokinetic (PK) estimate is only the first step in implementing tailored prophylaxis, which requires using the PK profile information to design a personalized treatment regimen matching the treatment needs of individual patients. The overarching goal of WAPPS-Hemo is to provide an easy-to-use web application supporting all the steps needed to accomplish tailoring care of individual patients by matching their unique characteristics to the most appropriate treatment regimen, realizing the promise of personalized medicine.
This study will assess the impact of adopting population PK (popPK) based tailored prophylaxis in clinical practice, including proportion of patients eligible for tailoring, and encountered barriers. The impact on patient important outcomes and on societal outcomes, particularly financial impact, vs. current standardized regimens will be measured. It is hypothesized that WAPPS-Hemo, via estimation of precise individual PK profiles and by supporting the simulation of treatment regimens will:
Read more
- improve or maintain patient important outcomes, while reducing wastage of factor concentrates; and
- establish best practices and effective knowledge translation strategies for the implementation of personalized medicine.
Additionally, a solid base of data will be generated to model the bleeding risk of severe hemophilia A/B patients undergoing tailored prophylaxis which will enable evaluation of a combination of patient and treatment characteristics predictive of individual bleeding risk.
Read the detailed description
The PMCH study is a Canadian multicentre, open-label, historically-controlled clinical trial to evaluate the effects of implementing WAPPS-Hemo PopPK-based tailoring of hemophilia prophylaxis regimens using the tailoring dosing function of the WAPPS-Hemo system (WAPPS-Hemo clinical calculator).
The study start date at each centre are staggered by 1-3 months in a modified wedge-shaped design, to allow better differentiation of the effect of the intervention from unrelated but concomitant changes in other aspects of care in the Canadian landscape. Outcomes of interest will be measured for one year prior and for one year after the implementation of the WAPPS-Hemo regimen tailoring procedure.
The two main objectives of this study are:
- Evaluate the applicability and effectiveness of WAPPS-Hemo PopPK-based tailoring of factor concentrate regimens.
- Generate a solid base of data to model the bleeding risk of severe hemophilia A/B patients on prophylaxis, evaluating the contribution of patient and treatment characteristics to individual bleeding risk to be reduced by the tailored prophylaxis approach.
PMCH will objectively measure the impact of adopting a PopPK based tailoring of hemophilia treatment. The first goal will be minimizing the occurrence of bleeding events in the hemophilia population. The bleeding rate of Canadian hemophilia patients is still measurable at 2-4 spontaneous joint bleeds per year, which in turn reduce quality of life and consume health resources. It is expected that optimizing treatment goal and modalities will reduce this burden, or at least will not increase it, allowing the pursuit the second goal: minimize the use of resources and prompt a more equitable distribution of factor concentrates. For some patients, standard prophylaxis dosing leads to excessive use of concentrates. It is expected that a small but sizeable proportion of the patient population will be able to successfully reduce their factor concentrate consumption. The third goal will be to generate an evidence-based approach to identify the appropriate target goal(s) for individual patients by modelling the components of their risk of bleeding. Adopting a variable target threshold may enhance objective one and two, maximizing benefits with appropriate allocation of resources.
In addition to WAPPS-Hemo, the study will involve two other tools available to hemophilia treaters in Canada: the Canadian Bleeding Disorders Registry (CBDR) and Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. In particular, this study will leverage the integration of the three tools described above: WAPPS-Hemo, with its ability to generate PK estimates and use them to optimize treatment regiments; CBDR, already collecting most of the information needed to both generate and estimate optimal regimen recommendations for tailoring an individual regimen to meet specified treatment goals; and PROBE, to measure the impact on patient critical life experiences and outcome.
- Conditions
- Hemophilia A, Hemophilia B
- Being tested
- Implementation of WAPPS-Hemo personalized dosing regimen
- Keywords
- pharmacokinetics, popPK, PK, Hemophilia
- Medical subject headings
- Hemophilia A, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implementation of WAPPS-Hemo personalized dosing regimenOther
Twelve months after enrollment in the study, WAPPS-Hemo will be used to calculate each patients individual pharmacokinetic estimate. Once completed, the WAPPS-Hemo clinical calculator will be used to calculate the optimal regimen based on individual needs.
| Study group | Role | What they receive |
|---|---|---|
| Tailored Regimen | Other | Implementation of WAPPS-Hemo personalized dosing regimen. Receives: Other: Implementation of WAPPS-Hemo personalized dosing regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in patient quality of life
Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. Scores range from 0-1, with a higher value indicating better health status.
Measured: Completed every 3-6 months for duration of the study, from enrollment to study completion.
Annualized Bleeding Rate (ABR) pre and post-tailoring implementation
ABR from the one year prior to WAPPS-Hemo tailoring to the one-year post-tailoring (absolute number of bleeds per year).
Measured: Recorded throughout the 2 year duration of the study as they occur.
Secondary outcomes (7)
Change in physical activity
Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. Scores range from 0-1, with a higher value indicating better health status.
Measured: Completed every 3-6 months for duration of the study, from enrollment to study completion.
Adherence to prescribed regimen
Measured by comparing the usage resulting from the prescribed regimen, the amount ordered for and dispensed to the patient and the amount logged on the treatment and bleeding diary.
Measured: Recorded throughout the 2 year duration of the study - frequency is as input by patient.
Consumption of factor concentrates
Measured as change from the amount prescribed and used before and after the adoption of tailoring.
Measured: Recorded throughout the 2 year duration of the study - frequency as input by patient.
Feasibility and acceptability of the WAPPS-Hemo based prophylaxis tailoring
Measured by proportion of cases with changes in prescribed regimens matching WAPPS-Hemo suggested regimens.
Measured: Recorded after 1 year at the time of tailoring implementation.
Characteristics of reported bleeds
Assessed by exploring information including distribution and typology of joint bleeds as reported in the patient bleed and treatment logs.
Measured: Recorded throughout the 2 year duration of the study- frequency as input by patient.
Assessment of the predictive performance of the WAPPS-Hemo clinical calculator
Measured by the comparison of predicted and observed post-infusion levels, when measured as part of routine clinical practice during the study period
Measured: Measured within routine clinical practice for 12 months post-tailoring implementation.
Change in joint function
Measured by the Hemophilia Joint Health Score (HJHS). Scores range from 0-124, with higher values indicating poorer joint health.
Measured: Measured at study enrollment and at 2 years at study completion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start24 Jul 2019
- Primary completion30 Sep 2022
- Study completion30 Sep 2023 (estimated)
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 McMaster UniversityThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The PMCH study is a Canadian multicentre, open-label, historically-controlled clinical trial to evaluate the effects of implementing WAPPS-Hemo PopPK-based tailoring of hemophilia prophylaxis regimens using the tailoring dosing function of the WAPPS-Hemo system (WAPPS-Hemo clinical calculator). The study has a non-inferiority design for the primary efficacy and safety outcomes.
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfonso Iorio, MD, PhD, FRCPC, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03615053
- Sponsor's protocol ID
- PMCH Study
- Acronym
- PMCH
- Status last verified
- Mar 2023
- First submitted
- 18 Jul 2018
- Last updated
- 21 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Medicine for Canadians With Hemophilia: a Pragmatic Evaluation of the Web-Accessible Population Pharmacokinetics Service- Hemophilia (WAPPS-Hemo) Tailored Dosing.
- ClinicalTrials.gov ID
- NCT03615053
- Acronym / sponsor ID
- PMCH / PMCH Study
- Conditions
- Hemophilia A, Hemophilia B
- Keywords
- pharmacokinetics, popPK, PK, Hemophilia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Sep 2023 (estimated)
- First posted
- 3 Aug 2018 (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.
Performing an individual pharmacokinetic (PK) estimate is only the first step in implementing tailored prophylaxis, which requires using the PK profile information to design a personalized treatment regimen matching the treatment needs of individual patients. The overarching goal of WAPPS-Hemo is to provide an easy-to-use web application supporting all the steps needed to accomplish tailoring care of individual patients by matching their unique characteristics to the most appropriate treatment regimen, realizing the promise of personalized medicine.
This study will assess the impact of adopting population PK (popPK) based tailored prophylaxis in clinical practice, including proportion of patients eligible for tailoring, and encountered barriers. The impact on patient important outcomes and on societal outcomes, particularly financial impact, vs. current standardized regimens will be measured. It is hypothesized that WAPPS-Hemo, via estimation of precise individual PK profiles and by supporting the simulation of treatment regimens will:
- improve or maintain patient important outcomes, while reducing wastage of factor concentrates; and
- establish best practices and effective knowledge translation strategies for the implementation of personalized medicine.
Additionally, a solid base of data will be generated to model the bleeding risk of severe hemophilia A/B patients undergoing tailored prophylaxis which will enable evaluation of a combination of patient and treatment characteristics predictive of individual bleeding risk.
Detailed description
The PMCH study is a Canadian multicentre, open-label, historically-controlled clinical trial to evaluate the effects of implementing WAPPS-Hemo PopPK-based tailoring of hemophilia prophylaxis regimens using the tailoring dosing function of the WAPPS-Hemo system (WAPPS-Hemo clinical calculator).
The study start date at each centre are staggered by 1-3 months in a modified wedge-shaped design, to allow better differentiation of the effect of the intervention from unrelated but concomitant changes in other aspects of care in the Canadian landscape. Outcomes of interest will be measured for one year prior and for one year after the implementation of the WAPPS-Hemo regimen tailoring procedure.
The two main objectives of this study are:
- Evaluate the applicability and effectiveness of WAPPS-Hemo PopPK-based tailoring of factor concentrate regimens.
- Generate a solid base of data to model the bleeding risk of severe hemophilia A/B patients on prophylaxis, evaluating the contribution of patient and treatment characteristics to individual bleeding risk to be reduced by the tailored prophylaxis approach.
PMCH will objectively measure the impact of adopting a PopPK based tailoring of hemophilia treatment. The first goal will be minimizing the occurrence of bleeding events in the hemophilia population. The bleeding rate of Canadian hemophilia patients is still measurable at 2-4 spontaneous joint bleeds per year, which in turn reduce quality of life and consume health resources. It is expected that optimizing treatment goal and modalities will reduce this burden, or at least will not increase it, allowing the pursuit the second goal: minimize the use of resources and prompt a more equitable distribution of factor concentrates. For some patients, standard prophylaxis dosing leads to excessive use of concentrates. It is expected that a small but sizeable proportion of the patient population will be able to successfully reduce their factor concentrate consumption. The third goal will be to generate an evidence-based approach to identify the appropriate target goal(s) for individual patients by modelling the components of their risk of bleeding. Adopting a variable target threshold may enhance objective one and two, maximizing benefits with appropriate allocation of resources.
In addition to WAPPS-Hemo, the study will involve two other tools available to hemophilia treaters in Canada: the Canadian Bleeding Disorders Registry (CBDR) and Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. In particular, this study will leverage the integration of the three tools described above: WAPPS-Hemo, with its ability to generate PK estimates and use them to optimize treatment regiments; CBDR, already collecting most of the information needed to both generate and estimate optimal regimen recommendations for tailoring an individual regimen to meet specified treatment goals; and PROBE, to measure the impact on patient critical life experiences and outcome.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The PMCH study is a Canadian multicentre, open-label, historically-controlled clinical trial to evaluate the effects of implementing WAPPS-Hemo PopPK-based tailoring of hemophilia prophylaxis regimens using the tailoring dosing function of the WAPPS-Hemo system (WAPPS-Hemo clinical calculator). The study has a non-inferiority design for the primary efficacy and safety outcomes.
| Arm | Type | Receives |
|---|---|---|
| Tailored Regimen | Other | Other: Implementation of WAPPS-Hemo personalized dosing regimenImplementation of WAPPS-Hemo personalized dosing regimen. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- individuals with severe congenital hemophilia A and B;
- on continuous factor prophylaxis;
- must be registered on CBDR (iCHIP in BC)
Key exclusion criteria (3 listed)
- a history of explicit and documented previous treatment tailoring based on pharmacokinetic profiling;
- another congenital or acquired bleeding disorders other than Hemophilia A or B;
- active inhibitors (> 5 Bethesda units) or currently undergoing immune tolerance induction.
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 |
|---|---|---|
| Implementation of WAPPS-Hemo personalized dosing regimenTwelve months after enrollment in the study, WAPPS-Hemo will be used to calculate each patients individual pharmacokinetic estimate. Once completed, the WAPPS-Hemo clinical calculator will be used to calculate the optimal regimen based on individual needs. | Other | Tailored Regimen |
Primary outcome
Change in patient quality of life
Time frame: Completed every 3-6 months for duration of the study, from enrollment to study completion.
Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. Scores range from 0-1, with a higher value indicating better health status.
Annualized Bleeding Rate (ABR) pre and post-tailoring implementation
Time frame: Recorded throughout the 2 year duration of the study as they occur.
ABR from the one year prior to WAPPS-Hemo tailoring to the one-year post-tailoring (absolute number of bleeds per year).
7 secondary outcomes
Change in physical activity
Time frame: Completed every 3-6 months for duration of the study, from enrollment to study completion.
Adherence to prescribed regimen
Time frame: Recorded throughout the 2 year duration of the study - frequency is as input by patient.
Consumption of factor concentrates
Time frame: Recorded throughout the 2 year duration of the study - frequency as input by patient.
Feasibility and acceptability of the WAPPS-Hemo based prophylaxis tailoring
Time frame: Recorded after 1 year at the time of tailoring implementation.
Characteristics of reported bleeds
Time frame: Recorded throughout the 2 year duration of the study- frequency as input by patient.
Assessment of the predictive performance of the WAPPS-Hemo clinical calculator
Time frame: Measured within routine clinical practice for 12 months post-tailoring implementation.
Change in joint function
Time frame: Measured at study enrollment and at 2 years at study completion.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
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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.
Noella Noronha, BSc contact
Alfonso Iorio, MD, PhD, FRCPC principal investigator
McMaster University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Implementation of WAPPS-Hemo personalized dosing regimen in people with Hemophilia A and Hemophilia B, run by McMaster University at 7 sites 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 3 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alfonso Iorio, MD, PhD, FRCPC (905-525-9140, iorioa@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in patient quality of life (time frame: Completed every 3-6 months for duration of the study, from enrollment to study completion.). 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 21 Mar 2023.