A Study in Children, Teenagers and Adults With Severe Hemophilia A Who Switched From Other Factor VIII Treatments to Adynovate

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Other: Non-Interventional

• Study Type: Observational
• Enrollment (Actual): 153

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton-Niagara Regional Hemophilia Treatment Centre

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

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).

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Other: Non-Interventional; This is a Non-Interventional Study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	approximately 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	approximately 72 months
Clearance (Cl) of Adynovate	Cl will be estimated based on the individual WAPPS PK profile.	approximately 72 months
Maximum Observed Drug Concentration (Cmax) of Adynovate	Cmax is as estimated based on the individual WAPPS PK profile.	approximately 72 months
Area Under the Curve (AUC) of Adynovate	AUC will be estimated based on the individual WAPPS PK profile.	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.	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.	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.	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.	approximately 72 months
Annualized Bleeding Rate (ABR)	ABR will be calculated as: number of bleeds*12/months of observation.	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.	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.	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.	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.	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).	approximately 72 months

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): November 30, 2021
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 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-660-4004; MACS-2020-061601 (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: Yes
• Studies a U.S. FDA-regulated device product: No