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NCT03370913: BMN 270-301

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

Completed Phase 3 Results posted Last updated 25 March 2025
What this trial tests

Phase 3 trial testing valoctocogene roxaparvovec in Hemophilia A in 144 participants. Completed in 20 November 2024.

Timeline
19 December 2017
Primary endpoint
16 November 2020
20 November 2024

Quick facts

Lead sponsorBioMarin Pharmaceutical
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment144
Start date19 December 2017
Primary completion16 November 2020
Estimated completion20 November 2024
Sites49 locations across France, Italy, South Africa, Belgium, Taiwan, United Kingdom, Germany, Israel

Drugs / interventions tested

Conditions studied

Sponsor

BioMarin Pharmaceutical — full company profile →

Who can join

18 and older, male only, with Hemophilia A. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP. Primary · Baseline to efficacy evaluation period (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 (St

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)-4.13± 6.93
Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP. Secondary · Baseline to 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 prod

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)-4.08± 6.57
Change From Baseline in FVIII Activity at Week 104 Secondary · Baseline to Week 104

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 recei

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)21.94± 33.04
Change From Baseline in Annualized FVIII Utilization in EEP. Secondary · Baseline to EEP

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 pla

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)-3891.27± 1761.16
Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 104 Secondary · Baseline to Week 104

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-Qo

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)7.01± 12.55
Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 104 Secondary · Baseline to Week 104

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-week

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)4.90± 13.78
Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 104 Secondary · Baseline to Week 104

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 Haem

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)10.29± 17.65
Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 104 Secondary · Baseline to Week 104

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-wee

GroupValue95% CI
BMN 270 (Valoctocogene Roxaparvovec)7.37± 15.17

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to data cutoff date 15 November 2021 (Two year data analysis).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BMN 270 (Valoctocogene Roxaparvovec)
Serious: 24/134 (18%)
Deaths: 1/134

Serious adverse events (39 terms)

ReactionSystemBMN 270 (Valoctocogene Rox…
Alanine aminotransferase increasedInvestigations
Anaphylactic reactionImmune system disorders
DiarrheaGastrointestinal disorders
GastroenteritisInfections and infestations
Rectal hemorrhageGastrointestinal disorders
Acetabulum fractureInjury, poisoning and procedural complications
ApneaRespiratory, thoracic and mediastinal disorders
ArthropathyMusculoskeletal and connective tissue disorders
CataractEye disorders
Completed suicidePsychiatric disorders
Coronary artery diseaseCardiac disorders
DepressionPsychiatric disorders
Diabetes mellitusMetabolism and nutrition disorders
DiverticulumGastrointestinal disorders
HemoperitoneumGastrointestinal disorders
Hand fractureInjury, poisoning and procedural complications
HypersensitivityImmune system disorders
HypertensionVascular disorders
InfectionInfections and infestations
InfluenzaInfections and infestations
Influenza A virus test positiveInvestigations
Lower limb fractureInjury, poisoning and procedural complications
Macular holeEye disorders
Major depressionPsychiatric disorders
NephrolithiasisRenal and urinary disorders
Other adverse events (55 terms — click to expand)

ReactionSystemBMN 270 (Valoctocogene Rox…
Alanine aminotransferase increasedInvestigations
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
FatigueGeneral disorders
AcneSkin and subcutaneous tissue disorders
Upper respiratory tract infectionInfections and infestations
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
InsomniaPsychiatric disorders
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Weight increasedInvestigations
VomitingGastrointestinal disorders
Blood creatine phosphokinase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
CushingoidEndocrine disorders
HypertensionVascular disorders
Muscle strainInjury, poisoning and procedural complications
RhinitisInfections and infestations
FolliculitisInfections and infestations
Rash pustularInfections and infestations
DyspepsiaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
AnxietyPsychiatric disorders
Abdominal discomfortGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
PainGeneral disorders
Blood lactate dehydrogenase increasedInvestigations
ConstipationGastrointestinal disorders
ChillsGeneral disorders
DizzinessNervous system disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Limb injuryInjury, poisoning and procedural complications
ArthropathyMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Alanine aminotransferase increased, Anaphylactic reaction, Diarrhea, Gastroenteritis, Rectal hemorrhage, Acetabulum fracture, Apnea, Arthropathy.

Data from ClinicalTrials.gov NCT03370913 adverse events section.

Sponsor's own description

This Phase III clinical study will assess the impact of BMN 270 (compared to FVIII prophylaxis) on the number of bleeding episodes irrespective of exogenous FVIII replacement treatment in the efficacy evaluation period (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"). The study will also assess the impact of BMN 270 (compared to FVIII prophylaxis) on: the number of bleeding episodes requiring exogenous FVIII treatment in "Post FVIII Prophylaxis to Last Visit", FVIII activity as measured by chromogenic sustrate assay at Week 104 following intravenous infusion of BMN 270, usage of exogenous FVIII replacement therapy in "Post FVIII Prophylaxis to Last Visit", health-related quality of life patient-reported outcomes at week 104 following intravenous infusion of BMN 270. The study will also evaluate the safety of the BMN 270.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A.
    Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, et al · · 2022 · cited 296× · PMID 35294811 · DOI 10.1056/nejmoa2113708
  2. Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders.
    Shahryari A, Saghaeian Jazi M, Mohammadi S, Razavi Nikoo H, et al · · 2019 · cited 168× · PMID 31608113 · DOI 10.3389/fgene.2019.00868
  3. Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A.
    Mahlangu J, Kaczmarek R, von Drygalski A, Shapiro S, et al · · 2023 · cited 151× · PMID 36812433 · DOI 10.1056/nejmoa2211075
  4. Update on clinical gene therapy for hemophilia.
    Perrin GQ, Herzog RW, Markusic DM. · · 2019 · cited 128× · PMID 30559260 · DOI 10.1182/blood-2018-07-820720
  5. Adeno-Associated Virus Gene Therapy for Hemophilia.
    Samelson-Jones BJ, George LA. · · 2023 · cited 97× · PMID 36103998 · DOI 10.1146/annurev-med-043021-033013
  6. A Molecular Revolution in the Treatment of Hemophilia.
    Butterfield JSS, Hege KM, Herzog RW, Kaczmarek R. · · 2020 · cited 76× · PMID 31843450 · DOI 10.1016/j.ymthe.2019.11.006
  7. Gene therapy for hemophilia.
    Nathwani AC. · · 2022 · cited 74× · PMID 36485127 · DOI 10.1182/hematology.2022000388
  8. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A.
    Pasi KJ, Laffan M, Rangarajan S, Robinson TM, et al · · 2021 · cited 71× · PMID 34378280 · DOI 10.1111/hae.14391

Verify or expand the search:

Other trials of valoctocogene roxaparvovec

Trials testing the same drug.

Other recruiting trials for Hemophilia A

Currently open trials in the same condition.

Other BioMarin Pharmaceutical trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03370913.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing