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This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in combination with prophylactic corticosteroids in patients with severe hemophilia A.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| valoctocogene roxaparvovec | Experimental | Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| valoctocogene roxaparvovec | Biological | Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in FVIII Activity as Measured by Chromogenic Substrate Assay at Week 52. | The change from baseline (assuming no treatment for severe hemophilia A) in FVIII activity, as measured by chromogenic substrate assay (CSA), at Week 52 (during Weeks 49 - 52) post-BMN 270 infusion. Each participant's FVIII activity level at Week 52 is defined as the median of the values obtained within the analysis window at Weeks 49-52. The baseline value will be imputed as 1 IU/dL, since there will be no washout of severe hemophilia A participants' usual FVIII prophylaxis (in order to avoid increasing the risk of bleeding) prior to BMN 270 infusion. Post-BMN 270 infusion values for FVIII activity will be excluded from analysis if obtained within 72 hours (or 3 calendar days if time is not available) since the last infusion of exogenous FVIII replacement therapy. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. | Baseline to Week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Annualized Utilization of Exogenous FVIII Replacement Therapy in EEP | The change from baseline (prior to BMN 270 infusion while receiving FVIII prophylaxis) in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the efficacy evaluation period ("Post-FVIII Prophylaxis period"). The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). |
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Inclusion Criteria:
Exclusion Criteria:
Participants with detectable pre-existing antibodies to the adeno-associated virus (AAV5) capsid are excluded with the following exception: up to 25% of participants may have detectable pre-existing AAV5 capsid antibodies with titer level below the minimum required dilution (< 20).
Any evidence of active infection, including Coronavirus Disease (COVID-19), or any immunosuppressive disorder, except for HIV infection. HIV-positive patients who meet all other eligibility criteria may be included if they have a CD4 count > 200/mm^3 and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification by the testing laboratory's assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART.
Significant liver dysfunction with any of the following abnormal laboratory results: alanine aminotransferase (ALT) > 1.25x upper limit of normal (ULN);aspartate aminotransferase (AST) > 1.25x ULN;gamma-glutamyltransferase (GGT) > 1.25x ULN;Total bilirubin > 1.25x ULN;Alkaline phosphatase > 1.25x ULN; or international normalized ratio (INR) >= 1.4.
Participants whose liver laboratory assessments fall outside of these ranges could undergo repeat testing of the entire liver test panel within the same Screening window and, if eligibility criteria are met on retest, could be enrolled after confirmation by the Medical Monitor.
FibroScan or prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
Evidence of any bleeding disorder not related to hemophilia A.
Platelet count of < 100 x 10^9/L.
Creatinine >= 1.5 mg/dL
Liver cirrhosis or other clinically significant liver disease of any etiology as assessed by FibroScan or liver ultrasound.
Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], and hepatitis B core antibody [HBcAb]) and confirmatory hepatitis B virus (HBV) DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results in the Laboratory Manual.
Active Hepatitis C as evidenced by detectable hepatitis C virus (HCV) RNA or currently on antiviral therapy.
Active malignancy, except non-melanoma skin cancer.
History of hepatic malignancy.
History of arterial or venous thromboembolic events (eg, deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus), with the exception of catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing.
Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.
Treatment with any investigational product within 30 days or 5 half-lives of the investigational product prior to the screening period. For participants who have received a prior investigational product, all ongoing adverse events (AEs) experienced while receiving that investigational product must have resolved prior to screening for this study.
Any condition that, in the opinion of the Investigator or Sponsor would prevent the patient from fully complying with the requirements of the study (including possible corticosteroids (CS) treatment and/or use of alternative immunosuppressive agents (AIS) outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of participant safety or efficacy result.
Prior treatment with any vector or gene transfer agent.
Major surgery planned in the 52-week period following the infusion with BMN 270.
Use of systemic immunosuppressive agents, not including CS, or live vaccines within 30 days before the BMN 270 infusion.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol or have the potential to impact the evaluation of efficacy and safety of BMN 270 and with prior consultation with the Medical Monitor.
Known allergy or hypersensitivity to BMN 270 investigational product formulation.
Unwilling to receive blood or blood products for treatment of an adverse event and/or a bleeding episode.
Optional Liver Biopsy Inclusion and Exclusion Criteria
Individuals eligible for the optional liver biopsy must meet the following inclusion criteria:
Individuals who meet the following exclusion criterion are not be eligible for the optional liver biopsy:
1. Any condition that, in the opinion of the Investigator or a hepatologist/radiologist would make liver biopsy contraindicated. This includes (but is not limited to) abnormalities detected on liver ultrasound performed within 28 days of procedure, or prior liver ultrasound result within 90 days that would preclude safe performance of the biopsy
Biological males only
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor, MD | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Davis Health | Sacramento | California | 95817 | United States | ||
| Washington University School of Medicine |
Total of 34 subjects were screened. Of these, 12 subjects failed screening and remaining 22 subject was enrolled in the study. Of the 22 enrolled participants, all 22 completed the Week 52 visit, and all 22 remained enrolled in the study as on data cut-off date 27January2023.
While up to 25% of patients could be AAV5+, no such patients were enrolled, i.e., everyone was AAV5 negative.
This study was conducted by 12 principal investigators at 12 study centers in 4 countries (United States, Australia, Brazil, and Taiwan)
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| ID | Title | Description |
|---|---|---|
| FG000 | BMN 270 (valoctocogene roxaparvovec) | Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII, with Prophylactic Corticosteroids in Hemophilia A subjects |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 25, 2021 | Dec 14, 2023 |
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| Baseline to efficacy evaluation period (EEP) |
| Change From Baseline in the Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment (Annualized Bleeding Rate, ABR for All Bleeds) in EEP | All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. ABR for all bleeds= Number of bleeding episodes for all bleeds during the calculation period / total number of days during the calculation period * 365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). | Baseline to efficacy evaluation period (EEP) |
| Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment (ABR for Treated Bleeds) in the EEP. | ABR for treated bleeds=Number of bleeding episodes for treated bleeds during the calculation period/total number of days during the calculation period * 365.25 Bleeds that were treated with FVIII replacement therapy (recorded as "treatment for bleed") within 72 hours and were not associated with surgery or a procedure were included. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). | Baseline to EEP |
| Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 52 | The change from baseline(assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at wk52 post-BMN 270 infusion.The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life(HRQoL)questionnaire for adults consisting of 41 items covering 6 domains(Physical Functioning, Role Functioning,Worry,Consequences of Bleeding,Emotional Impact &Treatment Concerns). The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0(none of the time)to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-QoL-A domain(physical functioning, role functioning, worry, consequences of bleeding, emotional impact, treatment concern) scores range from 0 to 5 and the total score is derived by summing each domain score (range, 0 to 30). Domain and total scores are transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia related quality of life. | Baseline to Week 52 |
| Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 52 | The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 52 post BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-Qol-A physical functioning domain score is an average of each item value within a domain.The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The physical functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related physical functioning | Baseline to Week 52 |
| Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 52 | The change from baseline(assuming no treatment for severe hemophilia A)in Haemo-Qol-A score, at week 52 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life(HRQoL)questionnaire for adults consisting of 41 items covering 6 domains(Physical Functioning,Role Functioning,Worry,Consequences of Bleeding,Emotional Impact and Treatment Concerns). The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0(none of the time) to 5(all of the time). The recall period for the Haemo-Qol-A is one month (4-wks). The Haemo-Qol-A consequences of bleeding domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The consequences of bleeding domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related consequences of bleeding. | Baseline to Week 52 |
| Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 52 | The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 52 post BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time). The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-Qol-A role functioning domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The role functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related role functioning. | Baseline to Week 52 |
| St Louis |
| Missouri |
| 63110 |
| United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| The Royal Adelaide Hospital | Adelaide | Australia |
| Royal Brisbane and Women's Hospital | Brisbane | Australia |
| Alfred Hospital | Melbourne | Australia |
| Fiona Stanley Hospital | Perth | Australia |
| Royal Prince Alfred Hospital | Sydney | Australia |
| Campinas University Clinical Hospital | Campinas | Brazil |
| Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo | São Paulo | Brazil |
| Changhua Christian Medical Foundation Changhua Christian Hospital | Changhua | Taiwan |
| Taichung Veterans General Hospital | Taichung | Taiwan |
| Continuing in the study |
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| Completed Week 52 visit |
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| COMPLETED | Study is still ongoing. |
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| NOT COMPLETED |
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Intention-to-treat (ITT) population (N=22) - all participants who received BMN 270 infusion in 270-303 by the time of the data cutoff
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| ID | Title | Description |
|---|---|---|
| BG000 | BMN 270 (Valoctocogene Roxaparvovec) | Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII, with Prophylactic Corticosteroids in Hemophilia A subjects |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at enrollment, years | Mean | Standard Deviation | years |
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| Age, Customized | Age at enrollment: n(%) | Count of Participants | Participants |
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| Sex: Female, Male | Percentages were calculated using the total number of participants (N) in each analysis population as the denominator. | Count of Participants | Participants |
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| Race/Ethnicity, Customized | n(%) | Count of Participants | Participants |
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| Baseline annualized FVIII usage | The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25. | Mean | Standard Deviation | IU/kg/year |
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| Baseline annualized number of FVIII infusions | Annualized FVIII infusion rate (count/yr) = (sum(Number of FVIII replacement infusions during calculation period) /sum(follow-up days of the period))*365.25. | Mean | Standard Deviation | Infusions/year |
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| Baseline ABR (treated bleeds) | Bleeds that were treated with FVIII replacement therapy (recorded as "treatment for bleed") within 72 hours and were not associated with surgery or a procedure were included. Annualized bleed rate (episodes/yr) = (sum (number of bleed episodes during calculation period))/(sum (follow-up days of the period)) *365.25 | Mean | Standard Deviation | bleeds/year |
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| Baseline ABR (treated bleeds) | Bleeds that were treated with FVIII replacement therapy (recorded as "treatment for bleed") within 72 hours and were not associated with surgery or a procedure were included. Annualized bleed rate (episodes/yr) = (sum (number of bleed episodes during calculation period))/(sum (follow-up days of the period)) *365.25 | Count of Participants | Participants |
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| Baseline ABR (all bleeds) | All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. Annualized bleed rate (episodes/yr) = (sum (number of bleed episodes during calculation period))/(sum (follow-up days of the period)) *365.25 | Mean | Standard Deviation | bleeds/year |
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| Baseline ABR (all bleeds) | All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. Annualized bleed rate (episodes/yr) = (sum (number of bleed episodes during calculation period))/(sum (follow-up days of the period)) *365.25 | Count of Participants | Participants |
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| History of previous diseases | n(%) | Count of Participants | Participants |
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| Number of target joints | n(%) Target joints are defined as joints with >= 3 spontaneous treated bleeds in the same joint location within any consecutive 6-month (180 days) period in the Baseline period. | Count of Participants | Participants |
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| Adeno-associated virus Type 5 (AAV5) Total Antibody Titers and Positivity | Percentages were calculated using the number of subjects with non-missing assessments (n) for each analysis population as the denominator. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline in FVIII Activity as Measured by Chromogenic Substrate Assay at Week 52. | The change from baseline (assuming no treatment for severe hemophilia A) in FVIII activity, as measured by chromogenic substrate assay (CSA), at Week 52 (during Weeks 49 - 52) post-BMN 270 infusion. Each participant's FVIII activity level at Week 52 is defined as the median of the values obtained within the analysis window at Weeks 49-52. The baseline value will be imputed as 1 IU/dL, since there will be no washout of severe hemophilia A participants' usual FVIII prophylaxis (in order to avoid increasing the risk of bleeding) prior to BMN 270 infusion. Post-BMN 270 infusion values for FVIII activity will be excluded from analysis if obtained within 72 hours (or 3 calendar days if time is not available) since the last infusion of exogenous FVIII replacement therapy. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. | Modified intention-to-treat (mITT) population (N=21) - all participants who received BMN 270 infusion in 270-303 and were on adequate prophylactic hemophilia therapy for at least 12 months (adequate prophylaxis was defined as >= 52 doses of FVIII replacement therapy in 12 months if on FVIII prophylaxis) prior to BMN 270 infusion. | Posted | Mean | Standard Deviation | IU /dL | Baseline to Week 52 |
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| Secondary | Change From Baseline in Annualized Utilization of Exogenous FVIII Replacement Therapy in EEP | The change from baseline (prior to BMN 270 infusion while receiving FVIII prophylaxis) in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the efficacy evaluation period ("Post-FVIII Prophylaxis period"). The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). | mITT population | Posted | Mean | Standard Deviation | IU/kg/yr | Baseline to efficacy evaluation period (EEP) |
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| Secondary | Change From Baseline in the Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment (Annualized Bleeding Rate, ABR for All Bleeds) in EEP | All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. ABR for all bleeds= Number of bleeding episodes for all bleeds during the calculation period / total number of days during the calculation period * 365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). | mITT population | Posted | Mean | Standard Deviation | bleeds/year | Baseline to efficacy evaluation period (EEP) |
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| Secondary | Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment (ABR for Treated Bleeds) in the EEP. | ABR for treated bleeds=Number of bleeding episodes for treated bleeds during the calculation period/total number of days during the calculation period * 365.25 Bleeds that were treated with FVIII replacement therapy (recorded as "treatment for bleed") within 72 hours and were not associated with surgery or a procedure were included. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). | mITT population | Posted | Mean | Standard Deviation | bleeds/year | Baseline to EEP |
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| Secondary | Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 52 | The change from baseline(assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at wk52 post-BMN 270 infusion.The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life(HRQoL)questionnaire for adults consisting of 41 items covering 6 domains(Physical Functioning, Role Functioning,Worry,Consequences of Bleeding,Emotional Impact &Treatment Concerns). The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0(none of the time)to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-QoL-A domain(physical functioning, role functioning, worry, consequences of bleeding, emotional impact, treatment concern) scores range from 0 to 5 and the total score is derived by summing each domain score (range, 0 to 30). Domain and total scores are transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia related quality of life. | mITT population | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 52 |
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| Secondary | Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 52 | The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 52 post BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-Qol-A physical functioning domain score is an average of each item value within a domain.The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The physical functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related physical functioning | mITT population | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 52 |
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| Secondary | Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 52 | The change from baseline(assuming no treatment for severe hemophilia A)in Haemo-Qol-A score, at week 52 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life(HRQoL)questionnaire for adults consisting of 41 items covering 6 domains(Physical Functioning,Role Functioning,Worry,Consequences of Bleeding,Emotional Impact and Treatment Concerns). The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0(none of the time) to 5(all of the time). The recall period for the Haemo-Qol-A is one month (4-wks). The Haemo-Qol-A consequences of bleeding domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The consequences of bleeding domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related consequences of bleeding. | mITT population | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 52 |
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| Secondary | Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 52 | The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 52 post BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time). The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-Qol-A role functioning domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The role functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related role functioning. | mITT population | Posted | Mean | Standard Deviation | Score on a scale | Baseline to Week 52 |
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Up to 112 weeks
Intention-to-treat (ITT) population (N=22) - all participants who received BMN 270 infusion in 270-303 by the time of the data cutoff
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BMN 270 (Valoctocogene Roxaparvovec) | Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A | 0 | 22 | 1 | 22 | 22 | 22 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Head injury | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Pregnancy of partner | Social circumstances | MedDRA 24.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tara M Robinson, MD, PhD, Senior Medical Director, Late-Stage Clinical Development | BioMarin Pharmaceutical Inc. | 415-455-7931 | tara.robinson@bmrn.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 20, 2023 | Dec 14, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| D020141 | Hemostatic Disorders |
| D006402 | Hematologic Diseases |
| D001778 | Blood Coagulation Disorders |
| D025861 | Blood Coagulation Disorders, Inherited |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D006425 | Hemic and Lymphatic Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000723395 | Valoctocogene Roxaparvovec |
Not provided
Not provided
Not provided
| >= 50 years |
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| White |
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| >4 to 10 bleeds/year |
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| >10 bleeds/year |
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| >4 to 10 |
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| >10 |
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| HIV |
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| No History of exposure to Hepatitis B/Hepatitis C/HIV |
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| 2 |
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| 3 |
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