Trial Outcomes & Findings for Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5 (NCT NCT03520712)

NCT ID: NCT03520712

Last Updated: 2025-08-22

Results Overview

A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Up to 5 years post-infusion.

Results posted on

2025-08-22

Participant Flow

This study was conducted by 2 principal investigators at 2 study centers in 2 countries (South Africa and United Kingdom). Nine investigational sites were activated, 2 subjects in South Africa and 1 subject in the United Kingdom were enrolled in the study.

10 participants were planned to be enrolled. 3 participants met all eligibility criteria \& were enrolled in study. There were 26 screen failures.

Participant milestones

Participant milestones
Measure	BMN 270 6E13 vg/kg BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Overall Study STARTED	3
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	BMN 270 6E13 vg/kg BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Overall Study Early termination of the study by Sponsor	2

Baseline Characteristics

Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BMN 270 6E13 vg/kg n=3 Participants BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	3 Participants n=99 Participants
Race/Ethnicity, Customized White Non-Hispanic	2 Participants n=99 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=99 Participants
Region of Enrollment United Kingdom	1 participants n=99 Participants
Region of Enrollment South Africa	2 participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 5 years post-infusion.

Population: The safety analysis was based on the ITT population. The intention-to-treat (ITT) population was comprised of all participants who have received the BMN 270 infusion.

A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

Outcome measures

Outcome measures
Measure	BMN 270 6E13 vg/kg n=3 Participants BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Number of Participants With Treatment Emergent Adverse Events Participants with any AE	3 Participants
Number of Participants With Treatment Emergent Adverse Events Participants with any SAE	1 Participants
Number of Participants With Treatment Emergent Adverse Events Participants with any treatment-related AE	3 Participants
Number of Participants With Treatment Emergent Adverse Events Treatment-related SAEs	1 Participants
Number of Participants With Treatment Emergent Adverse Events Participants with any AE of Grade >= 3	1 Participants
Number of Participants With Treatment Emergent Adverse Events AEs leading to dose adjustment during infusion	0 Participants
Number of Participants With Treatment Emergent Adverse Events AEs leading to dose interruption during infusion	0 Participants
Number of Participants With Treatment Emergent Adverse Events AEs leading to study drug discontinuation	0 Participants
Number of Participants With Treatment Emergent Adverse Events Participants who died	0 Participants

SECONDARY outcome

Timeframe: 26 weeks

Population: The intention-to-treat (ITT) population was comprised of all participants who have received the BMN 270 infusion.

Prior to BMN270 infusion, screening FVIII activity levels where participants had not received exogenous FVIII within 72 hours of assessment were below the lower limit of quantitation (LLOQ) as measured by CSA (LLOQ = 0.015 IU/mL).

Outcome measures

Outcome measures
Measure	BMN 270 6E13 vg/kg n=3 Participants BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Number of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA). Participant with FVIII activity >= 5 IU/dL	1 Participants
Number of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA). Participant with FVIII activity < 5 IU/dL	2 Participants

SECONDARY outcome

Timeframe: Week 5 and Beyond (Follow-Up, up to 1782 Days)

Population: The intention-to-treat (ITT) population was comprised of all participants who have received the BMN 270 infusion.

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

Outcome measures

Outcome measures
Measure	BMN 270 6E13 vg/kg n=3 Participants BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Mean Annualized Factor VIII Utilization During Week 5 and Beyond	661.1 IU/kg/yr Standard Deviation 912.92

SECONDARY outcome

Timeframe: Week 5 and Beyond (Follow-Up, up to 1782 Days)

Population: The intention-to-treat (ITT) population was comprised of all participants who have received the BMN 270 infusion.

Annualized FVIII replacement infusion rate=(number of FVFIII replacement infusions during calculation period/sum(follow-up days) of the period)\*365.25

Outcome measures

Outcome measures
Measure	BMN 270 6E13 vg/kg n=3 Participants BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Mean Annualized Factor VIII Infusion Rate During Week 5 and Beyond	21.9 ml/min Standard Deviation 30.61

SECONDARY outcome

Timeframe: Week 5 and Beyond (Follow-Up, up to 1782 Days)

Population: The intention-to-treat (ITT) population was comprised of all participants who have received the BMN 270 infusion.

Annualized bleeding rate (ABR) (counts/yr.)=Number of bleeding episodes during calculation period/Total number of days during the calculation period ×365.25

Outcome measures

Outcome measures
Measure	BMN 270 6E13 vg/kg n=3 Participants BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Number of Participants Showed Reduction in the ABR Post-BMN 270 Infusion. Impact of BMN 270 on the Number of Bleeding Episodes Requiring Exogenous FVIII Therapy. Participants showed reduction in the ABR post-BMN 270 infusion	3 Participants
Number of Participants Showed Reduction in the ABR Post-BMN 270 Infusion. Impact of BMN 270 on the Number of Bleeding Episodes Requiring Exogenous FVIII Therapy. Participants who did not show reduction in the ABR post-BMN 270 infusion	0 Participants

Adverse Events

BMN 270 6E13 vg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BMN 270 6E13 vg/kg n=3 participants at risk BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Immune system disorders Hypersensitivity	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

Other adverse events

Other adverse events
Measure	BMN 270 6E13 vg/kg n=3 participants at risk BMN 270 6E13 vg/kg, given as a single intravenous dose (IV) Valoctocogene Roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Investigations Alanine aminotransferase increased	66.7% 2/3 • Number of events 3 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • Number of events 3 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Immune system disorders Hypersensitivity	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Injury, poisoning and procedural complications Animal scratch	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Injury, poisoning and procedural complications Face injury	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Infections and infestations Onychomycosis	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Musculoskeletal and connective tissue disorders Tendon disorder	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Infections and infestations Covid-19	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Infections and infestations Conjunctivitis viral	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Injury, poisoning and procedural complications Limb injury	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Injury, poisoning and procedural complications Skin abrasion	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Injury, poisoning and procedural complications Muscle injury	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Infections and infestations Gastrointestinal infection	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
General disorders Hernia	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Injury, poisoning and procedural complications Thermal burns	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.
Infections and infestations Influenza	33.3% 1/3 • Number of events 1 • up to 5 years post-infusion. The safety analysis was based on the ITT population. A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

Additional Information

Konstantia-Maria Chavele, PhD, Director, Clinical Sciences

BioMarin Pharmaceutical (UK) Ltd.

Phone: +44207

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60