A Study of Standard and Individualized Prophylactic Treatment With Advate in Men and Boys With Severe Hemophilia A (HAPKIDO)

Local, Multicenter, Non-interventional, Ambispective Study in Severe Hemophilia A Patients on Standard and PK-tailored Prophylaxis With Octocog Alfa (Advate®) in the Russian Federation

The main aim of this study is to learn about changes in the lowest blood levels of Factor VIII in men and boys when upgraded from standard prophylaxis with Advate to individualized prophylaxis with Advate.

No study medicines will be provided to participants in this study. The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study. Participants will need to visit the study doctor 3 times in total during the study. During these visits, study data will be collected by the study doctor.

Study Overview

• Status: Completed
• Conditions: Hemophilia A

Detailed Description

Local, Multicenter, Non-interventional, Ambispective Study in Severe Hemophilia A Patients on Standard and PK-tailored Prophylaxis With Octocog Alfa (Advate®) in the Russian Federation

• Study Type: Observational
• Enrollment (Actual): 94

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Children's Clinical Hospital
  • Khabarovsk, Russian Federation, 680003
    • Children's Regional Clinical Hospital
  • Krasnoyarsk, Russian Federation, 660074
    • Krasnoyarsk Regional Clinical Center for Maternal and Child Health
  • Moscow, Russian Federation, 119049
    • Morozovskaya Children's City Clinical Hospital of the Department of Healthcare of the city of Moscow
  • Nalchik, Russian Federation, 360032
    • State Budgetary Institution of Healthcare "Republican children's clinical hospital" of the Ministry of Health of the Kabardino-Balkar Republic
  • Novosibirsk, Russian Federation, 630087
    • State Novosibirsk Regional Clinical Hospital
  • Rostov-on-Don, Russian Federation, 344015
    • Regional Children's Clinical Hospital
  • St. Petersburg, Russian Federation, 191186
    • City Polyclinic No. 37
  • Vladivostok, Russian Federation, 690002
    • Regional Children's Clinical Hospital No. 1
  • Volgograd, Russian Federation, 400138
    • Volgograd Regional Clinical Oncological Dispensary
  • Voronezh, Russian Federation, 394024
    • Voronezh Regional Children's Clinical Hospital No. 1
  • Yekaterinburg, Russian Federation, 620149
    • State Autonomous Healthcare Institution of the Sverdlovsk Region "Regional Children's Clinical Hospital"
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420034
      • City Children's Hospital No. 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Male participants of all ages being treated with octocog alfa (Advate) for severe hemophilia A in 2021 will be enrolled in this study.

Description

Inclusion Criteria:

• Male participants of all ages with severe hemophilia A (FVIII ˂1%) or moderate hemophilia A with severe bleeding phenotype who:

  • had been on standard prophylaxis or PK-tailored prophylaxis with octocog alfa during at least 12 months prior to the study enrollment (150 participants) or who started Advate® treatment in 2021 (20 participants),
  • is being treated with octocog alfa at the moment of enrolment with any of the above mentioned treatment modalities, and
  • had been assigned octocog alfa provision in Federal reimbursement program 2021
• Availability of participants' records sufficient for data collection according to the study objectives during the retrospective period of the study for participants who had been on standard prophylaxis or PK-tailored prophylaxis with octocog alfa during at least 12 months prior to the study enrollment
• Written informed consent provided by the participant or, in case of children below 14 years of age, by participant's parent or participant's legally acceptable representative.

Exclusion Criteria:

• Failure to obtain the participant's written informed consent
• Participation in any interventional study of products for hemophilia or other hemostasis disturbances treatment during 12 months prior to the study enrollment for participants who has retrospective data collection period and during 12 months after the study enrollment for all participants.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
All Participants; Male participants with severe or moderate hemophilia A who have been treated with FVIII concentrate octocog alfa (Advate) during at least 12 months prior to the study enrollment, who started octocog alfa treatment in 2021 or currently being treated with octocog alfa will be observed in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time per Week Spent With Factor VIII (FVIII) Trough Level Below 1 Percent (%) on the Standard Prophylaxis and After Pharmacokinetic (PK) -tailored Prophylaxis	PK-tailoring prophylaxis is defined as FVIII replacement prophylactic therapy based on PK parameters of each particular participant. Time per week spent with Through FVIII level below 1% on standard and PK-tailored prophylaxis will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With More Than 19 Hours per Week Spent With FVIII Trough Level Below 1% on Standard Prophylaxis Versus on PK-tailored Prophylaxis	Percentage of participants with more than 19 hours per week with FVIII trough level below 1% on standard and PK-tailored prophylaxis will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Percentage of Participants With Upgraded Dosing Regimen Based on PK-assessment	Upgraded dosing regimen includes dose upgrade, dosing intervals modification, and/or FVIII trough level upgrade to above 1%. Percentage of participants with upgraded dosing regimen based on PK-assessment will be reported.	Baseline up to Visit 3 (Month 12)
Percentage of Time per Week Spent With FVIII Trough Level Below 1%, 1 to less than (<) 3%, and Greater Than or Equal to (>=) 3% While on Standard and Individualized Prophylaxis	Individualized prophylaxis is defined as prophylactic therapy based on PK parameters of each individual participant. Percentage of time per week spent with FVIII through level below 1%, 1- <3%, and >=3% while on standard and individualized prophylaxis will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Percentage of Participants With FVIII Trough Level Permanently Above 1% on Standard Prophylaxis vs on PK-tailored Prophylaxis	Percentage of participants with FVIII trough level permanently above 1% on standard and PK-tailored prophylaxis will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Correlation Between the Time per Week Spent With FVIII Trough Level Below 1% and Spontaneous Annualized Bleeding Rate (ABR) on Standard Prophylaxis	Correlation between the time per week spent with FVIII trough level below 1% and spontaneous ABR on standard prophylaxis will be assessed using Pearson's correlation coefficient.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Correlation Between the Time per Week Spent With FVIII Trough Level Below 1% and Spontaneous Annualized Joint Bleeding Rate (AJBR) on Standard Prophylaxis	Correlation between the time per week spent with FVIII trough level below 1% and spontaneous AJBR on standard prophylaxis will be assessed using Pearson's correlation coefficient.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Total Consumption of FVIII Before and After PK-tailored Prophylaxis in Participants With Upgraded Dosing Regimen	Total consumption of FVIII before and after PK-tailored prophylaxis in participants with upgraded dosing regimen will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Percentage of Participants With Positive Dynamics of Body Status After Transfer From Standard to Individualized Prophylaxis	Positive dynamics of body status is related with increased physical activity (change in body mass index [BMI], waist: hip ratio [WHR]. Percentage of participants with positive dynamics of body status after transfer from standard to individualized prophylaxis will be reported.	Baseline up to Visit 3 (Month 12)
Percentage of Participants Categorized Based on Number of Hospitalizations due to Insufficient Bleeding Control Before and After PK-tailored Prophylaxis	Percentage of participants categorized based on number of hospitalization due to insufficient bleeding control before and after PK-tailored Prophylaxis will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)
Percentage of Participants Categorized Based on Number of Days Away From Work and School/Institute Due to Insufficient Bleeding Control Before and After PK-tailored Prophylaxis	Percentage of participants categorized based on number of days away from work and school/institute due to insufficient bleeding control before and after PK-tailored prophylaxis will be reported.	From 12 months prior to study enrollment up to Visit 3 (Month 12)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2021
• Primary Completion (Actual): April 4, 2023
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: TAK-761-4001; MACS-2020-051901 (Other Identifier: Takeda)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No