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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03392974




Registration number
NCT03392974
Ethics application status
Date submitted
22/12/2017
Date registered
8/01/2018
Date last updated
30/05/2019

Titles & IDs
Public title
Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg
Scientific title
Phase 3 Study To Evaluate Efficacy/Safety of Valoctocogene Roxaparvovec an AAV Vector-Mediated Gene Transfer of hFVIII at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels =1IU/dL Receiving Prophylactic FVIII Infusions
Secondary ID [1] 0 0
2017-003573-34
Secondary ID [2] 0 0
BMN 270-302
Universal Trial Number (UTN)
Trial acronym
BMN270-302
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Valoctocogene Roxaparvovec

Experimental: Valoctocogene Roxaparvovec Open Label - Single administration of valoctocogene roxaparvovec at a dose of 4E13 vg/kg


Other interventions: Valoctocogene Roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change of the median Factor VIII (FVIII) activity
Timepoint [1] 0 0
52 Weeks
Secondary outcome [1] 0 0
Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment
Timepoint [2] 0 0
52 weeks

Eligibility
Key inclusion criteria
- Males = 18 years of age with hemophilia A and residual FVIII levels = 1 IU/dL as
evidenced by medical history, at the time of signing the informed consent.

- Must have been on prophylactic FVIII replacement therapy for at least 12 months prior
to study entry. High-quality, well-documented historical data concerning bleeding
episodes and FVIII usage over the previous 12 months must be available.

- Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure
days (EDs).

- No previous documented history of a detectable FVIII inhibitor, and results from a
Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda
Units (BU) (or less than 1.0 BU for laboratories with a historical lower sensitivity
cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week
apart within the past 12 months (at least one of which should be tested at the central
laboratory).
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Detectable pre-existing antibodies to the AAV5 capsid.

- Any evidence of active infection or any immunosuppressive disorder, including HIV
infection.

- Significant liver dysfunction with any of the following abnormal laboratory results:

- ALT (alanine aminotransferase) > 1.25x ULN;

- AST (aspartate aminotransferase) > 1.25x ULN;

- GGT (gamma-glutamyltransferase) >1.25x ULN

- Total bilirubin >1.25x ULN;

- Alkaline phosphatase >1.25x ULN; or

- INR (international normalized ratio) = 1.4.

Subjects whose liver laboratory assessments fall outside of these ranges may undergo repeat
testing of the entire liver test panel within the same Screening window and, if eligibility
criteria are met on retest, may be enrolled after confirmation by the Medical Monitor.

- 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 of any etiology as assessed by liver ultrasound.

- Chronic or active hepatitis B as evidenced by positive serology testing and
confirmatory 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 HCV RNA or currently on antiviral
therapy.

- Active malignancy, except non-melanoma skin cancer.

- History of hepatic malignancy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Adelaide Hospital (RAH) - Adelaide
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
The Canberra Hospital - Canberra
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [6] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Canberra
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Perth
Recruitment postcode(s) [6] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
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United States of America
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Florida
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United States of America
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Illinois
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United States of America
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Louisiana
Country [6] 0 0
United States of America
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Michigan
Country [7] 0 0
United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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Ohio
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United States of America
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Pennsylvania
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United States of America
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Tennessee
Country [12] 0 0
Belgium
State/province [12] 0 0
Brussels
Country [13] 0 0
Belgium
State/province [13] 0 0
Edegem
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Brazil
State/province [15] 0 0
Campinas
Country [16] 0 0
Brazil
State/province [16] 0 0
Curitiba
Country [17] 0 0
Brazil
State/province [17] 0 0
Rio De Janeiro
Country [18] 0 0
Brazil
State/province [18] 0 0
São Paulo
Country [19] 0 0
Brazil
State/province [19] 0 0
Vitória
Country [20] 0 0
France
State/province [20] 0 0
Brest
Country [21] 0 0
France
State/province [21] 0 0
Le Kremlin-Bicêtre
Country [22] 0 0
France
State/province [22] 0 0
Lille
Country [23] 0 0
France
State/province [23] 0 0
Marquillies
Country [24] 0 0
France
State/province [24] 0 0
Nantes
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France
State/province [25] 0 0
Paris
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Germany
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Berlin
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Germany
State/province [27] 0 0
Bonn
Country [28] 0 0
Germany
State/province [28] 0 0
Frankfurt-am-Main
Country [29] 0 0
Israel
State/province [29] 0 0
Tel HaShomer
Country [30] 0 0
Italy
State/province [30] 0 0
Florence
Country [31] 0 0
Italy
State/province [31] 0 0
Milan
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Busan
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Daegu
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Ulsan
Country [36] 0 0
South Africa
State/province [36] 0 0
Cape Town
Country [37] 0 0
South Africa
State/province [37] 0 0
Johannesburg
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Spain
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A Coruña
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Seville
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Taiwan
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Changhua
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Taipei
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United Kingdom
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Birmingham
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United Kingdom
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Cambridge
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United Kingdom
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Glasgow
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United Kingdom
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London
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United Kingdom
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Oxford
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United Kingdom
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Southampton
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United Kingdom
State/province [53] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BioMarin Pharmaceutical
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This clinical trial is being conducted to learn more about a potential treatment
(valoctocogene roxaparvovec) for people with severe hemophilia A. This research study will
test and confirm the safety and effectiveness of the 4E13 vg/kg dose of the study drug
(valoctocogene roxaparvovec) that contains the correct gene to make Factor VIII so that the
body can make its own Factor VIII that functions properly. Only one dose of valoctocogene
roxaparvovec is being given in this study, and this dose has been previously studied in
another clinical trial in patients with hemophilia A. This is a phase 3 study which is meant
to show that the study drug is safe and works to help treat hemophilia A. The study will see
if liver cells are able to make Factor VIII that functions properly after receiving this
study drug. The study will also examine the effects that the study drug has on how much
Factor VIII concentrates patients have to inject into their veins and on their bleeding
episodes after the study drug has been administered. Finally, the study will see if and how
the body responds to the study drug - for example, whether liver cells become inflamed or
whether the body makes antibodies (something the immune system makes to protect itself
against things like bacteria and viruses) against the vector or the new Factor VIII gene.
Trial website
https://clinicaltrials.gov/show/NCT03392974
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director, MD
Address 0 0
BioMarin Pharmaceutical
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Specialist
Address 0 0
Country 0 0
Phone 0 0
1-800-983-4587
Fax 0 0
Email 0 0
medinfo@bmrn.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03392974