Patient-reported Outcomes in Subjects Treated With ReFacto AF Routine Prophylaxis

NON-INTERVENTIONAL STUDY TO ASSESS THE HEALTH-RELATED QUALITY OF LIFE IN SEVERE OR MODERATELY SEVERE HEMOPHILIA A SUBJECTS TREATED WITH REFACTO AF ROUTINE PROPHYLAXIS

This NIS aims to assess the patient-reported outcomes (PROs) in enrolled subjects

Study Overview

• Status: Withdrawn
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: Refacto AF

Detailed Description

The design of the study is observational: both prospective and retrospective, national, multicenter, non- interventional. During this observational study, subjects diagnosed with severe or moderately severe (with severe phenotype) hemophilia A receiving routine prophylaxis treatment with ReFacto AF as per local standard clinical care, and in line with local labeling, are to be observed for 12 months.

The primary objective is to assess the health-related quality of life in subjects treated with ReFacto AF routine prophylaxis at baseline and after 6 and 12 months.

The secondary objectives are:

• To assess the subjective physical functioning of subjects treated with ReFacto AF routine prophylaxis at baseline and after 6 and 12 months;
• To assess the treatment satisfaction of caregivers of children and subjects above 18 years treated with ReFacto AF routine prophylaxis at baseline and after 6 and 12 months;
• To determine in routine clinical practice the mean annualized bleeding rate (ABR) in subjects treated with ReFacto AF routine prophylaxis;
• To describe the status of joint health measured by HJHS before and after starting routine prophylaxis for subjects above 18 years.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Subjects receiving routine prophylaxis treatment with ReFacto AF as determined by the inclusion criteria will be included in the study.

Description

Inclusion Criteria:

1. Severe (FVIII: C <1%) or moderately severe (FVIII: C ≥1 - ≤2% with severe phenotype [at least 4 spontaneous bleeds clinically documented during a 6 months period] and without inhibitors) male subjects with hemophilia A receiving routine prophylaxis treatment.

2. Age:

   • From 2 to 18 years;
   • Subjects above 18 years who began routine prophylaxis treatment in childhood (and were part of the national prophylaxis program when turned 18 years).
3. Previously treated patients (PTPs) with hemophilia A. Previously treated patient (PTP) is considered in this study as a subject who has at least 50 exposure days to any FVIII product. An exposure day (ED) is a 24-hour period during which a dose of FVIII concentrate has been administered, irrespective of size and frequency.
4. No history and no current FVIII inhibitor defined as a titer ≥0.6 BU/mL or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay.
5. Subjects who are scheduled by their treating physician to initiate prophylaxis with ReFacto AF or to continue previously initiated prophylaxis with ReFacto AF, and subjects who are switching from prophylaxis with another FVIII product to ReFacto AF.
6. Evidence of a personally signed and dated informed consent and assent (for children 6-17 years of age) document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

Main Exclusion Criteria:

1. Subject has known hypersensitivity to the active substance or any of the excipients.
2. Subject has known allergic reaction to hamster proteins.
3. Presence of any bleeding disorder in addition to hemophilia A.
4. Treatment with any investigational agent or device within the past 30 days.
5. Any other contraindications according to Summary of Product Characteristics (SPC).
6. Unsuitable to participate in study for any other reason as assessed by the investigator.
7. Subjects (or a legally acceptable representative) not able to understand study documents and study procedure.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1. Refacto AF (NIS); Non-Interventional Study	Drug: Refacto AF; Observational - Non-Interventional Study; Other Names: moroctocog alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The health-related quality of life in subjects treated with ReFacto AF routine prophylaxis	HRQoL will be assessed by applying the self-reported hemophilia-specific quality of life Haemo-QoL questionnaire. The endpoint will include the domains and total scores of the questionnaire. The results of this study will be presented using descriptive statistics and there will be no hypothesis testing. The domain scores and total scores will be summarized by: N, mean (sd), median, min-max and the 95% confidence interval at baseline, end of study, and the change from baseline.	Baseline and after 6 and 12 months.
The health-related quality of life	HRQoL will be be evaluated also by recording the number of days of absence from kindergarten, school or high-school. There are no a priori hypotheses specified and results will be presented as descriptive statistics.	Baseline and after 6 and 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The subjective physical functioning of subjects treated with ReFacto AF routine prophylaxis	Subjects will be asked to report their subjective physical functioning using the HEP-Test-Q. The endpoint will include the domains and total scores of the questionnaire. The results of this study will be presented using descriptive statistics and there will be no hypothesis testing. The domain scores and total scores will be summarized by: N, mean (sd), median, min-max and the 95% confidence interval at baseline, end of study, and the change from baseline.	Baseline and after 6 and 12 months;
The treatment satisfaction of caregivers of children and subjects above 18 years treated with ReFacto AF routine prophylaxis	Caregivers will evaluate their satisfaction with the treatment of their child and the above 18 years subjects will evaluate their own satisfaction with the treatment using the Hemo-Satp questionnaire. The endpoint will include the domains and total scores of the questionnaire. The results of this study will be presented using descriptive statistics and there will be no hypothesis testing. The domain scores and total scores will be summarized by: N, mean (sd), median, min-max and the 95% confidence interval at baseline, end of study, and the change from baseline.	Baseline and after 6 and 12 months;
The mean annualized bleeding rate (ABR) in subjects treated with ReFacto AF routine prophylaxis;	ABR will be calculated at the end of the study based on the number of bleeds recorded during the 12-months observation period. The ABR will be presented as N, mean (sd), median, min-max and the 95% confidence interval.	After 12 months
Joint health for subjects above 18 years	Status of joint health will be described for subjects above 18 years using the HJHS (Hemophilia Joint Health Score) before and after starting routine prophylaxis. HJHS for one particular joint (elbow, knee or ankle) represents the sum between the joint totals and the global gait score.The minimum score is 0 and the maximum is 24. The joint totals is the sum between the scores for swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain and strength; the maximum score is 20. The global gait score evaluates walking, stairs, running and hopping in one leg; the maximum score is 4.	After 12 months

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2019
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: March 18, 2016
• First Posted (Estimate): March 24, 2016

Study Record Updates

• Last Update Posted (Actual): November 16, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

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; Coagulants; Factor VIII
• Other Study ID Numbers: B1831088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No