Long-Term Safety and Efficacy of rFVIIIFc in the Prevention and Treatment of Bleeding Episodes in Previously Treated Participants With Hemophilia A

Hemophilia A Clinical Trial

— ASPIRE  

Official title:

An Open-Label, Multicenter Evaluation of the Long-Term Safety and Efficacy of Recombinant Human Coagulation Factor VIII Fusion Protein (rFVIIIFc) in the Prevention and Treatment of Bleeding Episodes in Previously Treated Subjects With Hemophilia A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01454739
• Other study ID #: 8HA01EXT
• Secondary ID: 2011-003072-37
• Status: Completed
• Phase: Phase 3
• Start date: December 2011
• Est. completion date: October 2017

Study information

• Verified date: November 2018
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the long-term safety of recombinant human Factor VIII Fc fusion protein (rFVIIIFc) in participants with hemophilia A. The secondary objective of the study is to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding episodes in participants with hemophilia A.

Description:

Participant will follow either a prophylaxis or on-demand regimen. The starting dose in this study will be determined by the clinical profile of the participant in the preceding studies A-LONG - 997HA301 (NCT01181128), pediatric study 8HA02PED (NCT01458106), 997HA307 (NCT02083965) and 997HA309 (NCT02502149).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

Key Inclusion Criteria:

• Subjects who have completed previous rFVIIIFc studies (NCT01181128, NCT02083965, NCT01458106 and NCT02502149)

• Ability to understand purposes and risks of the study and to provide signed and dated informed consent (or assent, as applicable).

Key Exclusion Criteria:

• Confirmed positive high-titer inhibitor (=5.00 BU/mL).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• rFVIIIFc
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Melbourne	Victoria
Australia	Research site	Melbourne	Victoria
Australia	Research Site	Murdoch	Western Australia
Australia	Research Site	South Brisbane	Queensland
Australia	Research Site	Subiaco	Western Australia
Austria	Research Site	Vienna
Belgium	Research Site	Bruxelles	Brussels
Brazil	Research Site	Campinas	Sao Paulo
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
France	Research Site	Bron cedex	Rhone
Germany	Research Site	Berlin
Germany	Research Site	Bonn	Nordrhein Westfalen
Hong Kong	Children Cancer Centre	Hong Kong	New Territories
Hong Kong	Research Site	Hong Kong
Hong Kong	Sir Yue Kong Pao Center for Cancer	Hong Kong	New Territories
India	Research Site	Bangalore	Karnataka
India	Research Site	Ludhiana	Punjab
India	Research Site	New Delhi	Delhi
India	Research Site	Pune	Maharashtra
India	Research Site	Vellore	Tamilnadu
Ireland	Research Site	Dublin
Israel	Research Site	Ramat Gan
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Vicenza
Japan	Research Site	Kashihara-shi	Nara-Ken
Japan	Research Site	Kawasaki	Kanagawa-Ken
Japan	Research Site	Kitakyushu	Fukuoka-Ken
Japan	Research Site	Nagoya-shi	Aichi-Ken
Japan	Research Site	Shinjuku-ku	Tokyo-To
Japan	Research Site	Tokyo	Tokyo-To
Netherlands	Research Site	Groningen
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research site	Hamilton
New Zealand	Research Site	Palmerston North
New Zealand	Research site	Wellington
Poland	Research Site	Lublin
South Africa	Research Site	Cape Town	Western Cape
South Africa	Research Site	Johannesburg	Gauteng
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Sweden	Research Site	Göteborg
Switzerland	Research Site	Zuerich
United Kingdom	Research Site	Basingstoke	Hampshire
United Kingdom	Research Site	Cambridge	Cambridgeshire
United Kingdom	Research Site	Glasgow	Strathclyde
United Kingdom	Research Site	Glasgow	Strathclyde
United Kingdom	Research Site	Hamstead	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	London	Greater London
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	East Lansing	Michigan
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Iowa City	Iowa
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Diego	California
United States	Research Site	Seattle	Washington
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bioverativ Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Hong Kong,  India,  Ireland,  Israel,  Italy,  Japan,  Netherlands,  New Zealand,  Poland,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Any Positive Inhibitor Development	An inhibitor test result greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL), identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. Data was summarized by treatment regimen for participants from 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Secondary	Annualized Bleeding Rate (ABR)	ABR is annualized number of bleeding episodes per participant per year. Bleeding episodes were classified as spontaneous if participant records bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity and as traumatic if participant records bleeding event when there is known reason for bleed. ABR=(Number of bleeding episodes during efficacy period (EP)/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. ABR was summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Secondary	Annualized Spontaneous Joint Bleeding Episodes	Bleeding episodes were classified as spontaneous if participant records a bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity. In addition, location of bleed (joint, internal, skin/mucosa or muscle) were collected. Annualized spontaneous joint bleeding episodes=(Number of spontaneous joint bleeding episodes during efficacy period (EP)/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. Bleeding episodes were summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Secondary	Total Number of Exposure Days (EDs)	An exposure day is a 24-hour period in which one or more rFVIIIFc injections are given. The total number of days of exposure to rFVIIIFc were summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Secondary	Annualized rFVIIIFc Consumption (International Units Per Kilogram [IU/kg])	Annualized consumption = (total international unit per kilogram [IU/kg] of study treatment received during the efficacy period / total number of days during the efficacy period) multiplied by 365.25. Efficacy period 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. Annualized consumption was summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Secondary	Physicians' Global Assessment of Participant's Response to rFVIIIFc Regimen Using a 4-Point Scale	Participants were assessed for response to their rFVIIIFc regimen using following 4-point scale: 1=Excellent:bleeding episodes responded to less than or equal to (<=)usual number of injections/dose of rFVIIIFc or rate of breakthrough bleeding during prophylaxis was <= that usually observed; 2=Effective: most bleeding episodes responded to same number of injections and dose, but some required more injections or higher doses, or there was minor increase in rate of breakthrough; 3=Partially Effective: bleeding episodes most often required more injections and/or higher doses than expected or adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses and 4=Ineffective: routine failure to control hemostasis/hemostatic control require additional agents. Total number of scale responses =total count of scale responses for all participants; multiple responses per participant including those at scheduled and unscheduled visits are counted.	Approximately 5 years
Secondary	Participant's Assessment of Response (Excellent or Good Response) to rFVIIIFc Injections for the Treatment of Bleeding Episodes Using a 4-Point Scale	Using eDiary, participant received rating for treatment response to any bleeding episode (BE) using 4-point scale- 1=Excellent: Abrupt pain relief and/or improvement in signs of bleeding within approximately (approx.) 8 hours (h) after initial injection (inj.); 2=Good: Definite pain relief and/or improvement in signs of bleeding within approx. 8h after an injection, but possibly requiring more than 1 injection after 24-48h for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8h after initial injection and requires more than 1 injection and 4=None: No improvement, or condition worsens within approx. 8h after initial injection. This assessment was to be made approx. 8 to 12h from time the injection was given to treat BE and prior to any additional doses of rFVIIIFc given for same bleeding episode. Percentages are based on the number of bleeding episodes for which a response (excellent or good) was provided for the first injection during the efficacy period.	Approximately 5 years