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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: rFVIIIFc

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Research Site
    • Melbourne, Victoria, Australia, 3181
      • Research Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Research Site
    • Subiaco, Western Australia, Australia, 6008
      • Research Site
• Austria
  • Vienna, Austria, 1090
    • Research Site
• Belgium
  • Brussels
    • Bruxelles, Brussels, Belgium, 1200
      • Research Site
• Brazil
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-878
      • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Research Site
• France
  • Rhone
    • Bron cedex, Rhone, France, 69677
      • Research Site
• Germany
  • Berlin, Germany, 10249
    • Research Site
  • Nordrhein Westfalen
    • Bonn, Nordrhein Westfalen, Germany, 53127
      • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • New Territories
    • Hong Kong, New Territories, Hong Kong
      • Children Cancer Centre
    • Hong Kong, New Territories, Hong Kong
      • Sir Yue Kong Pao Center for Cancer
• India
  • Delhi
    • New Delhi, Delhi, India, 110002
      • Research Site
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • Research Site
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Research Site
  • Punjab
    • Ludhiana, Punjab, India, 141008
      • Research Site
  • Tamilnadu
    • Vellore, Tamilnadu, India, 632004
      • Research Site
• Ireland
  • Dublin, Ireland, D12 N512
    • Research Site
• Israel
  • Ramat Gan, Israel, 52621
    • Research Site
• Italy
  • Firenze, Italy, 50134
    • Research Site
  • Milano, Italy, 20122
    • Research Site
  • Vicenza, Italy, 36100
    • Research Site
• Japan
  • Aichi-Ken
    • Nagoya-shi, Aichi-Ken, Japan, 466-8560
      • Research Site
  • Fukuoka-Ken
    • Kitakyushu, Fukuoka-Ken, Japan, 807-8556
      • Research Site
  • Kanagawa-Ken
    • Kawasaki, Kanagawa-Ken, Japan, 216-8511
      • Research Site
  • Nara-Ken
    • Kashihara-shi, Nara-Ken, Japan, 634-8522
      • Research Site
  • Tokyo-To
    • Shinjuku-ku, Tokyo-To, Japan, 160-0023
      • Research Site
    • Tokyo, Tokyo-To, Japan, 167-8515
      • Research Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Research Site
• New Zealand
  • Auckland, New Zealand, 1023
    • Research Site
  • Christchurch, New Zealand, 8011
    • Research Site
  • Hamilton, New Zealand, 3200
    • Research Site
  • Palmerston North, New Zealand, 4410
    • Research Site
  • Wellington, New Zealand, 6021
    • Research Site
• Poland
  • Lublin, Poland, 20-093
    • Research Site
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Research Site
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
• Sweden
  • Göteborg, Sweden, 41345
    • Research Site
• Switzerland
  • Zuerich, Switzerland, 8091
    • Research Site
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Research Site
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Research Site
  • Greater London
    • London, Greater London, United Kingdom, E1 1BB
      • Research Site
    • London, Greater London, United Kingdom, SE1 7EH
      • Research Site
    • London, Greater London, United Kingdom, WC1N 3JH
      • Research Site
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Research Site
  • London
    • Hamstead, London, United Kingdom, NW3 2QG
      • Research Site
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G3 8SJ
      • Research Site
    • Glasgow, Strathclyde, United Kingdom, G4 0SF
      • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90007
      • Research Site
    • Los Angeles, California, United States, 90027
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
  • Michigan
    • East Lansing, Michigan, United States, 48823
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: On-Demand; The individual dose of rFVIIIFc to treat bleeding episodes will be based on participant's clinical condition, type and severity of the bleeding event, and if indicated, Factor VIII (FVIII) levels.	Drug: rFVIIIFc; Administered as specified in the treatment arm.; Other Names: Eloctate; recombinant coagulation factor VIII Fc fusion protein; BIIB031; antihemophilic factor (recombinant) Fc fusion protein; efmoroctocog alfa
Experimental: Prophylaxis; Tailored prophylaxis, Weekly prophylaxis or Personalized prophylaxis available.	Drug: rFVIIIFc; Administered as specified in the treatment arm.; Other Names: Eloctate; recombinant coagulation factor VIII Fc fusion protein; BIIB031; antihemophilic factor (recombinant) Fc fusion protein; efmoroctocog alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bioverativ Therapeutics Inc.
• Investigators: Study Director: Medical Director, Bioverativ Therapeutics Inc.

Publications and helpful links

General Publications

• Nolan B, Mahlangu J, Pabinger I, Young G, Konkle BA, Barnes C, Nogami K, Santagostino E, Pasi KJ, Khoo L, Winding B, Yuan H, Fruebis J, Rudin D, Oldenburg J. Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study. Haemophilia. 2020 May;26(3):494-502. doi: 10.1111/hae.13953. Epub 2020 Mar 30.
• Nolan B, Mahlangu J, Perry D, Young G, Liesner R, Konkle B, Rangarajan S, Brown S, Hanabusa H, Pasi KJ, Pabinger I, Jackson S, Cristiano LM, Li X, Pierce GF, Allen G. Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A. Haemophilia. 2016 Jan;22(1):72-80. doi: 10.1111/hae.12766. Epub 2015 Jul 27.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: September 29, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (Estimate): October 19, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: rFVIIIFc; A-LONG Extension
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: 8HA01EXT; 2011-003072-37

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No