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

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04876365
• Other study ID #: TAK-660-4004
• Secondary ID: MACS-2020-061601
• Status: Completed
• Start date: November 30, 2021
• Est. completion date: February 28, 2022

Study information

• Verified date: July 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: February 28, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Other:
• Non-Interventional
This is a Non-Interventional Study.

Locations

Country	Name	City	State
Canada	Hamilton-Niagara Regional Hemophilia Treatment Centre	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Canada, 

Outcome

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

External Links

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