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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02234323




Registration number
NCT02234323
Ethics application status
Date submitted
29/08/2014
Date registered
9/09/2014
Date last updated
11/04/2022

Titles & IDs
Public title
An Open Label Study to Determine the Safety and Efficacy of Replacement Factor VIII Protein (Known as rFVIIIFc) in Previously Untreated Males With Severe Hemophilia A
Scientific title
An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in the Prevention and Treatment of Bleeding in Previously Untreated Patients With Severe Hemophilia A
Secondary ID [1] 0 0
2013-005512-10
Secondary ID [2] 0 0
997HA306
Universal Trial Number (UTN)
Trial acronym
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 - rFVIIIFc

Experimental: rFVIIIFc - Participants were to receive rFVIIIFc as follows- Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3- to 5-day intervals until participant reached greater than or equal to (\>=) 50 exposure days (ED: 24-hour period in which \>=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (\>=5.00 Bethesda Units per milliliter \[BU/mL\]) or positive low titer inhibitor (\>=0.60 and \<5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.


Treatment: Other: rFVIIIFc
Administered as specified in arm description
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
Assessment method [1] 0 0
A positive/confirmed inhibitor result occurs when a participant has a value \>=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected \>=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached \>=10 EDs and had \>=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received \>=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
Assessment method [1] 0 0
ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent "strenuous" activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)\*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than \[\>\]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Annualized Number of Spontaneous Joint Bleeding Episodes
Assessment method [2] 0 0
Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent "strenuous" activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total number of days during EP)\*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (\> 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
Assessment method [3] 0 0
Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Total Number of Exposure Days (EDs)
Assessment method [4] 0 0
An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
Assessment method [5] 0 0
Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)\*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (\>28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode
Assessment method [6] 0 0
Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (\>28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode
Assessment method [7] 0 0
The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
Change From Baseline in rFVIIIFc Incremental Recovery (IR)
Assessment method [8] 0 0
Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter \[IU/dL\] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (\<)0.5 IU/dL was set to 0 IU/dL for calculation of IR.
Timepoint [8] 0 0
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
Secondary outcome [9] 0 0
Number of Participants With Response to Immune Tolerance Induction (ITI)
Assessment method [9] 0 0
Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR \>=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life \>=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.
Timepoint [9] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
Key

* Ability of the participant's legally authorized representative (e.g. their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
* Weight >=3.5 kg at the time of screening.
* Severe hemophilia A defined as less than (<) 1 IU/dL (<1%) endogenous FVIII documented in the medical record or as tested during the Screening Period.

Key
Minimum age
No limit
Maximum age
5 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Any exposure to blood components, factor VIII replacement products, including commercially available rFVIIIFc at any time prior to or during screening.
* History of positive inhibitor testing. A prior history of inhibitors was defined based on a patient's historical positive inhibitor test using the local laboratory Bethesda value for a positive inhibitor test (ie, equal to or above lower level of detection).
* History of hypersensitivity reactions associated with any rFVIIIFc administration.
* Other coagulation disorder(s) in addition to hemophilia A.
* Any concurrent clinically significant major disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment.
* Current systemic treatment with chemotherapy and/or other immunosuppressant drugs.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/09/2019
Sample size
Target
Accrual to date
Final
108
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Brisbane
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment hospital [3] 0 0
Research Site - Perth
Recruitment hospital [4] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
6008 - Perth
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Maine
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
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Brazil
State/province [15] 0 0
Campinas
Country [16] 0 0
Brazil
State/province [16] 0 0
Canoas
Country [17] 0 0
Brazil
State/province [17] 0 0
Ribeirão Preto
Country [18] 0 0
Brazil
State/province [18] 0 0
Rio de Janeiro
Country [19] 0 0
Brazil
State/province [19] 0 0
São Paulo
Country [20] 0 0
Canada
State/province [20] 0 0
Hamilton
Country [21] 0 0
Canada
State/province [21] 0 0
London
Country [22] 0 0
Canada
State/province [22] 0 0
Toronto
Country [23] 0 0
France
State/province [23] 0 0
Caen cedex 9
Country [24] 0 0
France
State/province [24] 0 0
Le Kremlin Bicêtre cedex
Country [25] 0 0
France
State/province [25] 0 0
Lille Cedex
Country [26] 0 0
France
State/province [26] 0 0
Nantes Cedex 1
Country [27] 0 0
France
State/province [27] 0 0
Strasbourg
Country [28] 0 0
France
State/province [28] 0 0
Toulouse cedex
Country [29] 0 0
France
State/province [29] 0 0
Tours cedex 9
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Bonn
Country [32] 0 0
Germany
State/province [32] 0 0
Duesseldorf
Country [33] 0 0
Germany
State/province [33] 0 0
Frankfurt
Country [34] 0 0
Germany
State/province [34] 0 0
Hannöver
Country [35] 0 0
Ireland
State/province [35] 0 0
Dublin
Country [36] 0 0
Italy
State/province [36] 0 0
VI
Country [37] 0 0
Italy
State/province [37] 0 0
Bari
Country [38] 0 0
Italy
State/province [38] 0 0
Florence
Country [39] 0 0
Italy
State/province [39] 0 0
Genova
Country [40] 0 0
Italy
State/province [40] 0 0
Milan
Country [41] 0 0
Italy
State/province [41] 0 0
Napoli
Country [42] 0 0
Italy
State/province [42] 0 0
Padova
Country [43] 0 0
Italy
State/province [43] 0 0
Rome
Country [44] 0 0
Netherlands
State/province [44] 0 0
Leiden
Country [45] 0 0
Netherlands
State/province [45] 0 0
Utrecht
Country [46] 0 0
New Zealand
State/province [46] 0 0
Auckland
Country [47] 0 0
New Zealand
State/province [47] 0 0
Christchurch
Country [48] 0 0
Poland
State/province [48] 0 0
Gdansk
Country [49] 0 0
Poland
State/province [49] 0 0
Kraków
Country [50] 0 0
Poland
State/province [50] 0 0
Lublin
Country [51] 0 0
Poland
State/province [51] 0 0
Warszawa
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Sweden
State/province [54] 0 0
Stockholm
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Cambridgeshire
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Hampshire
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Cardiff
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bioverativ, a Sanofi company
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Swedish Orphan Biovitrum
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02234323