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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03370913




Registration number
NCT03370913
Ethics application status
Date submitted
27/11/2017
Date registered
13/12/2017
Date last updated
20/12/2023

Titles & IDs
Public title
Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)
Scientific title
A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels = 1 IU/dL Receiving Prophylactic FVIII Infusions
Secondary ID [1] 0 0
2017-003215-19
Secondary ID [2] 0 0
270-301
Universal Trial Number (UTN)
Trial acronym
BMN 270-301
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
Treatment: Other - valoctocogene roxaparvovec

Experimental: valoctocogene roxaparvovec Open Label - Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg


Treatment: Other: valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.
Timepoint [1] 0 0
Baseline to efficacy evaluation period (EEP)
Secondary outcome [1] 0 0
Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP.
Timepoint [1] 0 0
Baseline to EEP
Secondary outcome [2] 0 0
Change From Baseline in FVIII Activity at Week 104
Timepoint [2] 0 0
Baseline to Week 104
Secondary outcome [3] 0 0
Change From Baseline in Annualized FVIII Utilization in EEP.
Timepoint [3] 0 0
Baseline to EEP
Secondary outcome [4] 0 0
Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 104
Timepoint [4] 0 0
Baseline to Week 104
Secondary outcome [5] 0 0
Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 104
Timepoint [5] 0 0
Baseline to Week 104
Secondary outcome [6] 0 0
Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 104
Timepoint [6] 0 0
Baseline to Week 104
Secondary outcome [7] 0 0
Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 104
Timepoint [7] 0 0
Baseline to Week 104

Eligibility
Key inclusion criteria
1. 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.
2. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.
3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).
4. 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) on 2 consecutive occasions at least one week apart within the past 12 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Detectable pre-existing antibodies to the adeno-associated virus 5 (AAV5) capsid.
2. Any evidence of active infection or any immunosuppressive disorder, except for HIV infection
3. Any evidence of active infection or any immunosuppressive disorder, including HIV infection (effective as of Protocol Amendment 3)
4. Significant liver dysfunction.
5. Prior liver biopsy showing significant fibrosis.
6. Evidence of any bleeding disorder not related to hemophilia A.
7. Platelet count of < 100 x 10^9/L.
8. Creatinine = 1.5 mg/dL.
9. Liver cirrhosis of any etiology as assessed by liver ultrasound.
10. Chronic or active hepatitis B.
11. Active Hepatitis C.
12. Active malignancy, except non-melanoma skin cancer.
13. History of hepatic malignancy.
14. History of arterial or venous thromboembolic events.
15. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2024
Actual
Sample size
Target
Accrual to date
Final
144
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
Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [5] 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
- Melbourne
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment postcode(s) [5] 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
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Brazil
State/province [12] 0 0
Campinas
Country [13] 0 0
Brazil
State/province [13] 0 0
Curitiba
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio De Janeiro
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Brazil
State/province [16] 0 0
Vitória
Country [17] 0 0
France
State/province [17] 0 0
Lille
Country [18] 0 0
France
State/province [18] 0 0
Marseille
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Germany
State/province [20] 0 0
Bonn
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Italy
State/province [22] 0 0
Milan
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
South Africa
State/province [24] 0 0
Johannesburg
Country [25] 0 0
Spain
State/province [25] 0 0
A Coruna
Country [26] 0 0
Spain
State/province [26] 0 0
Seville
Country [27] 0 0
Taiwan
State/province [27] 0 0
Changhua
Country [28] 0 0
Taiwan
State/province [28] 0 0
Kaohsiung
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taichung
Country [30] 0 0
Taiwan
State/province [30] 0 0
Taipei
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Birmingham
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Cambridge
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Glasgow
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Oxford
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Southampton

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

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03370913
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor, 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03370913