Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec in Patients With Hemophilia A or B Respectively

Study Overview
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Brief Summary
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A study to learn about the long-term safety and efficacy of giroctocogene fitelparvovec or fidanacogene elaparvovec in patients with hemophilia A or hemophilia B respectively, who have received treatment through prior participation in a Pfizer-sponsored clinical trial. Data collection and participant visits will be based on standard of care.

Official Title
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A PHASE 3, NON-INVESTIGATIONAL PRODUCT, MULTI COUNTRY COHORT STUDY TO DESCRIBE THE LONG-TERM SAFETY AND EFFECTIVENESS OF A PRIOR SINGLE-DOSE TREATMENT WITH INVESTIGATIVE GIROCTOCOGENE FITELPARVOVEC OR FIDANACOGENE ELAPARVOVEC IN PARTICIPANTS WITH HEMOPHILIA A OR HEMOPHILIA B, RESPECTIVELY

Conditions
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Hemophilia A, Hemophilia B

Intervention / Treatment
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* Diagnostic Test: Testing of hepatic AAV Vector integration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Only participants who received investigational giroctocogene fitelparvovec or fidanacogene eleparvovec and were enrolled in a Pfizer-sponsored study (C0371002, C0371003, C0371005, C3731001, C3731003) are eligible. Exclusion Criteria: -None

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Non-investigational study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hemophilia A / giroctocogene fitelparvovec<br>Participants have received treatment with giroctocogene fitelparvovec in a previous study and are not receiving any investigational product in this study | Diagnostic Test: Testing of hepatic AAV Vector integration<br>* Evaluation of AAV vector integration in participants for whom a sample of liver has been obtained through biopsy or surgical resection when clinically indicated<br>|
| Other: Hemophilia B / fidanacogene elaparvovec<br>Participants have received treatment with fidanacogene elaparvovec in a previous study and are not receiving any investigational product in this study | Diagnostic Test: Testing of hepatic AAV Vector integration<br>* Evaluation of AAV vector integration in participants for whom a sample of liver has been obtained through biopsy or surgical resection when clinically indicated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of thromboembolic events |  | Day 1 to 10 years | 
| Incidence of factor inhibitor development | FIX inhibitor development was defined as an inhibitor titer >= 0.6 Bethesda units per milliliter (BU/mL). | Day 1 to 10 years | 
| Incidence of hepatic malignancy |  | Day 1 to 10 years | 
| Incidence of liver abnormalities |  | Day 1 to 10 years | 
| Factor activity level | Factor activity level will be reported. Factor levels may be measured using different assay methods including a one-stage assay or by chromogenic substrate assay and a second one-stage assay. | Day 1 to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total ABR (treated or untreated; (excluding bleeds related to surgery) | ABR (Annual Bleed Rate): number of bleeding episodes per year. This includes treated and untreated bleeds. The ABR or the annualized number of bleeding episodes per year, will be derived for each participant for each observation period by using the following formula: ABR = (Number of bleeds / Days in observation period) x 365.25 days/year. | Day 1 to 10 years | 
| Incidence of and time from vector infusion to resumption of prophylaxis | Describe incidence of resumption of prophylaxis resumption and the time (in days) to resumption of prophylaxis after receiving vector infusion. | Day 1 to 10 years | 
| AIR of exogenous factor (excluding infusions related to surgery) | The AIR or the annualized number of FIX infusions per year, will be derived for each participant for each observation period by using the following formula: AIR = (Number of FIX infusions / Days in observation period) x 365.25 days/year. | Day 1 to 10 years | 
| Consumption of exogenous factor (excluding infusions related to surgery) | The annualized TFC in international units (IU) will be derived for each participant for each observation period using the following formula: Annualized TFC = (Total units of FIX infused (IU)/ Days in observation period) x 365.25 days/year | Day 1 to 10 years | 
| Incidence of Non-hepatic malignancy |  | Day 1 to 10 years | 
| Incidence of Auto-immune disorders |  | Day 1 to 10 years | 
| Incidence of SAEs | An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; development of a clinical thrombotic event; development of factor inhibitor; development of a hepatic malignancy; development of drug-related elevated hepatic transaminases that fail to improve with immunosuppressive regimens; occurrence of a malignancy with reasonable possibility of being related to study drug. | Day 1 to 10 years | 
| All cause mortality | All-cause mortality was defined as the death due to any cause during the course of study. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Incidence rate of all-cause deaths was reported in this outcome measure. | Day 1 to 10 years | 
| EQ-5D-5L dimension and VAS scores | The EQ-5D-5L comprises a 5-item health status measure and a visual analog rating scale/feeling thermometer. Using the 5-dimensional Health State Classification, participants are asked to respond to five questions on different aspects of their health status that assess the following: Mobility Self-care Usual activities Pain/Discomfort Anxiety/Depression | Day 1 to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bleeding, giroctocogene fitelparvovec, fidanacogene elaparvovec, factor IX, adeno-associated virus based vector, gene therapy, factor VIII