Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301) (BMN 270-301)

• ClinicalTrials.gov Identifier: NCT03370913
• Recruitment Status: Active, not recruiting
• First Posted: December 13, 2017
• Results First Posted: November 28, 2023
• Last Update Posted: December 20, 2023
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia A
• Intervention: Biological: valoctocogene roxaparvovec
• Enrollment: 144

Participant Flow

Recruitment Details

This study was conducted at 48 sites worldwide (United States, Australia, Belgium, Brazil, France, Germany, Israel, Italy, South Korea, South Africa, Spain, Taiwan, and United Kingdom).

Pre-assignment Details

Total of 181 subjects were screened. Of these, 41 subjects were screened without prior participation in 270-902,140 subjects were screened after participating in 270-902. 37 subjects failed screening. Of the remaining 144 enrolled subjects in 270-301,134 were treated with BMN 270. 10 subjects enrolled but were not dosed [5 subjects who did not previously participate in 270-902(direct enrolled population and 5 subjects dosed in 270-301 who previously participated in 270-902(Rollover population)].

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Period Title: Overall Study
Started	134
Completed [1]	132
Not Completed	2
Reason Not Completed
Death	1
Lost to Follow-up	1
[1] Participants completed Week 104 Visit

Baseline Characteristics

Arm/Group Title		BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description		Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Baseline Participants		134
Baseline Analysis Population Description		Intent-to-Treat (ITT) Population (n=134): All subjects dosed in 270-301
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	134 participants
		31.7 (10.3)
		[1] Measure Description: Age at enrollment, years
Age, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	134 participants
18 to < 30 years		65 48.5%
30 to < 50 years		56 41.8%
>= 50 years		13 9.7%
		[1] Measure Description: Age at enrollment: n(%)
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	134 participants
	Female	0 0.0%
	Male	134 100.0%
		[1] Measure Description: n(%) Percentages were calculated using the total number of subjects (n) in each analysis population as the denominator
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	134 participants
	Hispanic or Latino	7 5.2%
	Not Hispanic or Latino	127 94.8%
	Unknown or Not Reported	0 0.0%
		[1] Measure Description: n(%)
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	134 participants
Asian		19 14.2%
Black or African-American		15 11.2%
Native Hawaiian or other Pacific Islander		1 0.7%
White		96 71.6%
Not provided due to patient privacy		3 2.2%
		[1] Measure Description: n(%)
Baseline annualized FVIII usage [1]; Mean (Standard Deviation); Unit of measure: IU/kg/year
	Number Analyzed	134 participants
		4113.69 (1738.92)
		[1] Measure Description: 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 annualized number of FVIII infusions [1]; Mean (Standard Deviation); Unit of measure: Infusions/year
	Number Analyzed	134 participants
		137.55 (57.04)
		[1] Measure Description: Annualized FVIII infusion rate (count/yr) = (sum(Number of FVIII replacement infusions during calculation period) /sum(follow-up days of the period))*365.25.
Baseline ABR (all bleeds) [1]; Mean (Standard Deviation); Unit of measure: Bleeds/year
	Number Analyzed	134 participants
		5.97 (11.06)
		[1] Measure Description: 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
Baseline ABR (all bleeds) [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	134 participants
0 bleeds/year		41 30.6%
> 0 to 4		40 29.9%
> 4 to 10		31 23.1%
> 10		22 16.4%
		[1] Measure Description: n(%) 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
Baseline ABR (treated bleeds) [1]; Mean (Standard Deviation); Unit of measure: Bleeds/year
	Number Analyzed	134 participants
		5.42 (9.96)
		[1] Measure Description: 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
Baseline ABR (treated bleeds) [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	134 participants
0 bleeds/year		43 32.1%
> 0 to 4		42 31.3%
> 4 to 10		29 21.6%
> 10		20 14.9%
		[1] Measure Description: n(%) 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
History of previous diseases [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	134 participants
Hepatitis B		20 14.9%
Hepatitis C		41 30.6%
HIV		2 1.5%
		[1] Measure Description: n(%)
Number of target joints [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	134 participants
0		97 72.4%
1		17 12.7%
2		9 6.7%
3		8 6.0%
> 3		3 2.2%
		[1] Measure Description: n(%) Target joints are defined as joints with >= 3 spontaneous bleeds (treated or untreated) in the same joint location within any consecutive 6-month (180 days) period in the Baseline period.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.
Description	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 the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Time Frame	Baseline to efficacy evaluation period (EEP)

Outcome Measure Data

Analysis Population Description

Rollover Population (n=112): Subjects who completed approximately 6 months participation in the non-interventional study 270-902 before enrolling in 270-301, were HIV-negative at study screening, and received BMN 270 infusion in 270-301.

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	112
Mean (Standard Deviation); Unit of Measure: bleeds/year
	-4.13 (6.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMN 270 (Valoctocogene Roxaparvovec)
	Comments	Change from baseline in the ABR for all bleeds (post-baseline EEP value - baseline value)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-values were for 2-sided test against 0.
	Method	t-test, 2 sided
	Comments	Superiority was tested by1-sample t-test to test null hypothesis that change is >=0. Only negative changes represent efficacy.
Method of Estimation	Estimation Parameter	% Reduction from Baseline
	Estimated Value	-77.0
	Estimation Comments	77% reduction

2. Secondary Outcome

Title	Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP.
Description	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 the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Time Frame	Baseline to EEP

Outcome Measure Data

Analysis Population Description

Rollover Population

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	112
Mean (Standard Deviation); Unit of Measure: bleeds/year
	-4.08 (6.57)

3. Secondary Outcome

Title	Change From Baseline in FVIII Activity at Week 104
Description	The change from baseline (assuming no treatment for severe hemophilia A) in FVIII activity, as measured by chromogenic substrate assay, at Weeks 104 post-BMN 270 infusion. Each subject's FVIII activity level at Week 104 is defined as the median of the values obtained at Week 104 with the analysis window defined. The baseline value is imputed as 1 IU/dL for each subject. Note: One of the subject's wk104 duplicate data issue was corrected in the 3 year analysis per which the mean (standard deviation) values are reported in outcome measure table. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) Population (n=132): All HIV-negative subjects at study screening who were dosed in 270-301.

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	132
Mean (Standard Deviation); Unit of Measure: IU/dL
	21.94 (33.04)

4. Secondary Outcome

Title	Change From Baseline in Annualized FVIII Utilization in EEP.
Description	The change from baseline in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the Post FVIII Prophylaxis to Last Visit in the EEP. 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 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Time Frame	Baseline to EEP

Outcome Measure Data

Analysis Population Description

Rollover population

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	112
Mean (Standard Deviation); Unit of Measure: IU/kg/yr
	-3891.27 (1761.16)

5. Secondary Outcome

Title	Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 104
Description	The change from baseline(assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at wk104 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.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT Population: Modified Intent-to-Treat Population - all HIV-negative subjects dosed in 270-301.

Change from baseline was based on the subjects with available measurements at both time points.

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	126
Mean (Standard Deviation); Unit of Measure: score on a scale
	7.01 (12.55)

6. Secondary Outcome

Title	Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 104
Description	The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 104 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
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population

Change from baseline was based on the subjects with available measurements at both time points.

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	129
Mean (Standard Deviation); Unit of Measure: score on a scale
	4.90 (13.78)

7. Secondary Outcome

Title	Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 104
Description	The change from baseline(assuming no treatment for severe hemophilia A)in Haemo-Qol-A score, at week 104 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
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population.

Change from baseline was based on the subjects with available measurements at both time points.

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	129
Mean (Standard Deviation); Unit of Measure: score on a scale
	10.29 (17.65)

8. Secondary Outcome

Title	Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 104
Description	The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 104 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.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population

Change from baseline was based on the subjects with available measurements at both time points.

Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description:	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
Overall Number of Participants Analyzed	128
Mean (Standard Deviation); Unit of Measure: Score on a scale
	7.37 (15.17)

Adverse Events

Time Frame	Up to data cutoff date 15 November 2021 (Two year data analysis).
Adverse Event Reporting Description	Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
Arm/Group Title	BMN 270 (Valoctocogene Roxaparvovec)
Arm/Group Description	Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
All-Cause Mortality
	BMN 270 (Valoctocogene Roxaparvovec)
	Affected / at Risk (%)
Total	1/134 (0.75%)
Serious Adverse Events
	BMN 270 (Valoctocogene Roxaparvovec)
	Affected / at Risk (%)	# Events
Total	24/134 (17.91%)
Cardiac disorders
Coronary artery disease † 1	1/134 (0.75%)	1
Eye disorders
Cataract † 1	1/134 (0.75%)	2
Macular hole † 1	1/134 (0.75%)	1
Retinal detachment † 1	1/134 (0.75%)	1
Gastrointestinal disorders
Diarrhea † 1	2/134 (1.49%)	2
Rectal hemorrhage † 1	2/134 (1.49%)	2
Diverticulum † 1	1/134 (0.75%)	1
Hemoperitoneum † 1	1/134 (0.75%)	1
General disorders
Non-cardiac chest pain † 1	1/134 (0.75%)	1
Pain † 1	1/134 (0.75%)	1
Peripheral swelling † 1	1/134 (0.75%)	1
Immune system disorders
Anaphylactic reaction † 1	2/134 (1.49%)	2
Hypersensitivity † 1	1/134 (0.75%)	1
Infections and infestations
Gastroenteritis † 1	2/134 (1.49%)	2
Infection † 1	1/134 (0.75%)	1
Influenza † 1	1/134 (0.75%)	1
Pneumonia † 1	1/134 (0.75%)	1
Pneumonia cytomegaloviral † 1	1/134 (0.75%)	1
Upper respiratory tract infection † 1	1/134 (0.75%)	1
Injury, poisoning and procedural complications
Acetabulum fracture † 1	1/134 (0.75%)	1
Hand fracture † 1	1/134 (0.75%)	1
Lower limb fracture † 1	1/134 (0.75%)	1
Periprosthetic fracture † 1	1/134 (0.75%)	1
Post-procedural hemorrhage † 1	1/134 (0.75%)	1
Skin laceration † 1	1/134 (0.75%)	2
Traumatic hematoma † 1	1/134 (0.75%)	1
Investigations
Alanine aminotransferase increased † 1	2/134 (1.49%)	2
Influenza A virus test positive † 1	1/134 (0.75%)	1
Metabolism and nutrition disorders
Diabetes mellitus † 1	1/134 (0.75%)	1
Steroid diabetes † 1	1/134 (0.75%)	1
Musculoskeletal and connective tissue disorders
Arthropathy † 1	1/134 (0.75%)	1
Nervous system disorders
Presyncope † 1	1/134 (0.75%)	1
Psychiatric disorders
Completed suicide † 1	1/134 (0.75%)	1
Depression † 1	1/134 (0.75%)	2
Major depression † 1	1/134 (0.75%)	1
Renal and urinary disorders
Nephrolithiasis † 1	1/134 (0.75%)	1
Respiratory, thoracic and mediastinal disorders
Apnea † 1	1/134 (0.75%)	1
Skin and subcutaneous tissue disorders
Rash maculopapular † 1	1/134 (0.75%)	1
Vascular disorders
Hypertension † 1	1/134 (0.75%)	1
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	BMN 270 (Valoctocogene Roxaparvovec)
	Affected / at Risk (%)	# Events
Total	134/134 (100.00%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	8/134 (5.97%)	8
Endocrine disorders
Cushingoid † 1	16/134 (11.94%)	16
Gastrointestinal disorders
Nausea † 1	51/134 (38.06%)	79
Diarrhoea † 1	28/134 (20.90%)	43
Vomiting † 1	21/134 (15.67%)	27
Dyspepsia † 1	11/134 (8.21%)	13
Abdominal discomfort † 1	10/134 (7.46%)	10
Abdominal pain upper † 1	10/134 (7.46%)	15
Constipation † 1	9/134 (6.72%)	12
Gastrooesophageal reflux disease † 1	8/134 (5.97%)	9
General disorders
Fatigue † 1	40/134 (29.85%)	53
Pyrexia † 1	31/134 (23.13%)	35
Pain † 1	10/134 (7.46%)	11
Chills † 1	9/134 (6.72%)	9
Influenza like illness † 1	7/134 (5.22%)	8
Malaise † 1	7/134 (5.22%)	8
Infections and infestations
Upper respiratory tract infection † 1	33/134 (24.63%)	45
Nasopharyngitis † 1	29/134 (21.64%)	52
Rhinitis † 1	12/134 (8.96%)	16
Folliculitis † 1	11/134 (8.21%)	13
Rash pustular † 1	11/134 (8.21%)	12
Gastroenteritis † 1	7/134 (5.22%)	8
Influenza † 1	7/134 (5.22%)	7
Viral infection † 1	7/134 (5.22%)	7
Injury, poisoning and procedural complications
Muscle strain † 1	13/134 (9.70%)	19
Limb injury † 1	9/134 (6.72%)	10
Contusion † 1	8/134 (5.97%)	11
Ligament sprain † 1	8/134 (5.97%)	8
Fall † 1	7/134 (5.22%)	9
Investigations
Alanine aminotransferase increased † 1	119/134 (88.81%)	385
Aspartate aminotransferase increased † 1	47/134 (35.07%)	104
Weight increased † 1	22/134 (16.42%)	36
Blood creatine phosphokinase increased † 1	17/134 (12.69%)	22
Blood lactate dehydrogenase increased † 1	9/134 (6.72%)	14
Musculoskeletal and connective tissue disorders
Arthralgia † 1	53/134 (39.55%)	105
Back pain † 1	25/134 (18.66%)	32
Myalgia † 1	17/134 (12.69%)	18
Pain in extremity † 1	16/134 (11.94%)	19
Arthropathy † 1	8/134 (5.97%)	8
Muscle spasms † 1	8/134 (5.97%)	8
Nervous system disorders
Headache † 1	55/134 (41.04%)	174
Dizziness † 1	9/134 (6.72%)	14
Lethargy † 1	8/134 (5.97%)	9
Migraine † 1	7/134 (5.22%)	8
Tremor † 1	7/134 (5.22%)	7
Psychiatric disorders
Insomnia † 1	27/134 (20.15%)	46
Anxiety † 1	11/134 (8.21%)	12
Irritability † 1	7/134 (5.22%)	8
Respiratory, thoracic and mediastinal disorders
Cough † 1	24/134 (17.91%)	33
Oropharyngeal pain † 1	24/134 (17.91%)	28
Rhinorrhoea † 1	9/134 (6.72%)	10
Nasal congestion † 1	8/134 (5.97%)	8
Skin and subcutaneous tissue disorders
Acne † 1	36/134 (26.87%)	45
Rash † 1	11/134 (8.21%)	11
Vascular disorders
Hypertension † 1	16/134 (11.94%)	20
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Tara Robinson, MD, PhD, Senior Medical Director, Clinical Sciences
• Organization: BioMarin Pharmaceutical Inc.
• Phone: 415-455-7931
• EMail: tara.robinson@bmrn.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Quinn J, Delaney KA, Wong WY, Miesbach W, Bullinger M. Psychometric Validation of the Haemo-QOL-A in Participants with Hemophilia A Treated with Gene Therapy. Patient Relat Outcome Meas. 2022 Jul 18;13:169-180. doi: 10.2147/PROM.S357555. eCollection 2022.

Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, Pipe SW, Madan B, Key NS, Pierce GF, O'Mahony B, Kaczmarek R, Henshaw J, Lawal A, Jayaram K, Huang M, Yang X, Wong WY, Kim B; GENEr8-1 Trial Group. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 2022 Mar 17;386(11):1013-1025. doi: 10.1056/NEJMoa2113708.

Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, Christianson T, Pasi KJ, Rangarajan S, Symington E, Giermasz A, Pierce GF, Kim B, Zoog SJ, Vettermann C. Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy. Blood. 2020 Nov 26;136(22):2524-2534. doi: 10.1182/blood.2020005683.

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT03370913
• Other Study ID Numbers: 270-301; 2017-003215-19 ( EudraCT Number )
• First Submitted: November 27, 2017
• First Posted: December 13, 2017
• Results First Submitted: July 17, 2023
• Results First Posted: November 28, 2023
• Last Update Posted: December 20, 2023