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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01181128




Registration number
NCT01181128
Ethics application status
Date submitted
12/08/2010
Date registered
13/08/2010
Date last updated
8/01/2021

Titles & IDs
Public title
Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A
Scientific title
A-LONG: An Open-Label, Multicenter Evaluation of the Safety, Pharmacokinetics, and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia A
Secondary ID [1] 0 0
997HA301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe 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: Drugs - Factor VIII (rFVIIIFc)
Treatment: Drugs - Advate®

Experimental: Individualized (Tailored) Prophylaxis - On rFVIIIFc Day 0, all participants underwent pharmacokinetic (PK) analysis with 50 IU/kg rFVIIIFc to estimate their PK parameters and guide the appropriate dose or interval of dosing. A subset of participants (Sequential PK subgroup) also had PK analyses performed with a single dose of 50 IU/kg Advate (Advate Day 0) within 8 weeks prior to rFVIIIFc Day 0. A >= 96 hour washout was performed before the PK dose of Advate or rFVIIIFc was administered. Repeat PK profiling with a single dose of 50 IU/kg rFVIIIFc was conducted at Week 14 or after 12 to 24 weeks of prophylaxis with rFVIIIFc.
After PK assessments, all participants started twice weekly treatment with 25 IU/kg of rFVIIIFc via intravenous (IV) injection on Day 1 and 50 IU/kg on Day 4, followed by individualized dose and interval modification within the range of 25 to 65 IU/kg every 3 to 5 days, as determined by rFVIIIFc PK analysis, to maintain a trough level of 1% to 3% (or higher, as clinically indicated) FVIII activity.

Experimental: Weekly Prophylaxis - 65 IU/kg of rFVIIIFc via IV injection every 7 days

Experimental: Episodic (On-Demand) Dosing - 10 to 50 IU/kg rFVIIIFc via IV injection, as required to treat a bleeding episode


Treatment: Drugs: Factor VIII (rFVIIIFc)


Treatment: Drugs: Advate®
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence Rate of FVIII Inhibitor Development
Timepoint [1] 0 0
up to 52 weeks ± 2 weeks
Primary outcome [2] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [2] 0 0
up to 52 weeks + 30 days ± 1 week
Primary outcome [3] 0 0
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values From Baseline
Timepoint [3] 0 0
up to 52 weeks ± 2 weeks
Primary outcome [4] 0 0
Number of Participants With Clinically Relevant Abnormalities in Vital Signs or Relevant Changes From Baseline in Vital Signs
Timepoint [4] 0 0
up to 52 weeks ± 2 weeks
Primary outcome [5] 0 0
Annualized Bleeding Rate
Timepoint [5] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Primary outcome [6] 0 0
Comparison of Annualized Bleeding Rates: Arm 1 Versus Arm 3
Timepoint [6] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Primary outcome [7] 0 0
Area Under the Curve (AUC) Per Dose (One-stage Clotting Assay)
Timepoint [7] 0 0
See Measure Description for complete time frame.
Primary outcome [8] 0 0
Elimination Half Life (t1/2; One-stage Clotting Assay)
Timepoint [8] 0 0
See Measure Description for complete time frame.
Primary outcome [9] 0 0
Clearance (CL; One-stage Clotting Assay)
Timepoint [9] 0 0
See Measure Description for complete time frame.
Primary outcome [10] 0 0
Mean Residence Time (MRT; One-stage Clotting Assay)
Timepoint [10] 0 0
See Measure Description for complete time frame.
Primary outcome [11] 0 0
Incremental Recovery (One-stage Clotting Assay)
Timepoint [11] 0 0
See Measure Description for complete time frame.
Secondary outcome [1] 0 0
Comparison of Annualized Bleeding Rates: Arm 2 Versus Arm 3
Timepoint [1] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [2] 0 0
Annualized rFVIIIFc Consumption Per Participant
Timepoint [2] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [3] 0 0
Participant Assessment of Response to Injections to Treat a Bleeding Episode
Timepoint [3] 0 0
up to 52 weeks ± 2 weeks
Secondary outcome [4] 0 0
Investigator's Assessment of Participants' Bleeding Response to rFVIIIFc Injection
Timepoint [4] 0 0
up to 52 weeks ± 2 weeks
Secondary outcome [5] 0 0
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa)
Timepoint [5] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [6] 0 0
Annualized Joint Bleeding Rate (Spontaneous and Traumatic)
Timepoint [6] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [7] 0 0
Number of Days From Last Treatment Injection to a New Bleeding Episode
Timepoint [7] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [8] 0 0
Number of Injections Required for Resolution of a Bleeding Episode
Timepoint [8] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [9] 0 0
Number of Injections Required for Resolution of a Bleeding Episode by Location of Bleed
Timepoint [9] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [10] 0 0
Total Dose Per Injection Required for Resolution of a Bleeding Episode by Location of Bleed
Timepoint [10] 0 0
up to 52 weeks ± 2 weeks (efficacy period as defined in description)
Secondary outcome [11] 0 0
Volume at Steady State (Vss; One-stage Clotting Assay)
Timepoint [11] 0 0
See Measure Description for complete time frame.
Secondary outcome [12] 0 0
Volume at Steady State (Vss; Two-stage Chromogenic Assay)
Timepoint [12] 0 0
See Measure Description for complete time frame.
Secondary outcome [13] 0 0
Time to 1% and 3% FVIII Activity (One-stage Clotting Assay)
Timepoint [13] 0 0
See Measure Description for complete time frame.
Secondary outcome [14] 0 0
Time to 1% and 3% FVIII Activity (Two-stage Chromogenic Assay)
Timepoint [14] 0 0
See Measure Description for complete time frame.
Secondary outcome [15] 0 0
Time at Maximum Activity (Tmax; One-stage Clotting Assay)
Timepoint [15] 0 0
See Measure Description for complete time frame.
Secondary outcome [16] 0 0
Time at Maximum Activity (Tmax; Two-stage Chromogenic Assay)
Timepoint [16] 0 0
See Measure Description for complete time frame.
Secondary outcome [17] 0 0
Area Under the Curve (AUC) Per Dose (Two-stage Chromogenic Assay)
Timepoint [17] 0 0
See Measure Description for complete time frame.
Secondary outcome [18] 0 0
Elimination Half Life (t1/2; Two-stage Chromogenic Assay)
Timepoint [18] 0 0
See Measure Description for complete time frame.
Secondary outcome [19] 0 0
Clearance (CL; Two-stage Chromogenic Assay)
Timepoint [19] 0 0
See Measure Description for complete time frame.
Secondary outcome [20] 0 0
Mean Residence Time (MRT; Two-stage Chromogenic Assay)
Timepoint [20] 0 0
See Measure Description for complete time frame.
Secondary outcome [21] 0 0
Incremental Recovery (Two-stage Chromogenic Assay)
Timepoint [21] 0 0
See Measure Description for complete time frame.
Secondary outcome [22] 0 0
Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 14
Timepoint [22] 0 0
Baseline, Week 14
Secondary outcome [23] 0 0
Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 28
Timepoint [23] 0 0
Baseline, Week 28
Secondary outcome [24] 0 0
Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 14 and Week 28 in Haemo-QoL III Total Score
Timepoint [24] 0 0
Baseline, Week 14, Week 28
Secondary outcome [25] 0 0
Investigators'/Surgeons' Assessment of Participants' Response to rFVIIIFc for Major Surgery
Timepoint [25] 0 0
up to 52 weeks
Secondary outcome [26] 0 0
Number of Injections Required to Maintain Hemostasis During Major Surgery
Timepoint [26] 0 0
up to 52 weeks
Secondary outcome [27] 0 0
Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery
Timepoint [27] 0 0
up to 52 weeks ± 2 weeks
Secondary outcome [28] 0 0
Estimated Total Blood Loss During Major Surgery
Timepoint [28] 0 0
up to 52 weeks ± 2 weeks
Secondary outcome [29] 0 0
Number of Transfusions Required Per Surgery
Timepoint [29] 0 0
up to 52 weeks ± 2 weeks

Eligibility
Key inclusion criteria
- Male, =12 years of age with weight at least 40 kg

- Diagnosed with severe hemophilia A, defined as <1 IU/dL (<1%) endogenous Factor VIII)

- History of at least 150 documented prior exposure days to any Factor VIII product

- Platelet count =100,000 cells/µL
Minimum age
12 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- History of Factor VIII inhibitors

- Kidney and liver dysfunction

- Diagnosed with other coagulation disorder(s) in addition to hemophilia A

- Prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV
immunoglobulin administration

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Parallel
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
1/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2012
Sample size
Target
Accrual to date
Final
165
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Adelaide
Recruitment hospital [3] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Perth
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
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Bruxelles
Country [19] 0 0
Brazil
State/province [19] 0 0
Campinas
Country [20] 0 0
Canada
State/province [20] 0 0
Calgary
Country [21] 0 0
Canada
State/province [21] 0 0
Toronto
Country [22] 0 0
Canada
State/province [22] 0 0
Vancouver
Country [23] 0 0
France
State/province [23] 0 0
Lyon Cedex 3
Country [24] 0 0
Germany
State/province [24] 0 0
BE
Country [25] 0 0
Germany
State/province [25] 0 0
Northwest
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Hong Kong
Country [27] 0 0
India
State/province [27] 0 0
Delhi
Country [28] 0 0
India
State/province [28] 0 0
Karna
Country [29] 0 0
India
State/province [29] 0 0
Mahara
Country [30] 0 0
India
State/province [30] 0 0
Punjab
Country [31] 0 0
India
State/province [31] 0 0
Tamilnadu
Country [32] 0 0
Israel
State/province [32] 0 0
Ramat Gan
Country [33] 0 0
Italy
State/province [33] 0 0
FI
Country [34] 0 0
Italy
State/province [34] 0 0
MI
Country [35] 0 0
Italy
State/province [35] 0 0
VI
Country [36] 0 0
Japan
State/province [36] 0 0
Kashihara-shi
Country [37] 0 0
Japan
State/province [37] 0 0
Kawasaki-shi
Country [38] 0 0
Japan
State/province [38] 0 0
Kitakyushu-shi
Country [39] 0 0
Japan
State/province [39] 0 0
Nagoya-shi
Country [40] 0 0
Japan
State/province [40] 0 0
Shinjuku-ku
Country [41] 0 0
Japan
State/province [41] 0 0
Suginami-ku
Country [42] 0 0
New Zealand
State/province [42] 0 0
Auckland
Country [43] 0 0
New Zealand
State/province [43] 0 0
Christchurch
Country [44] 0 0
New Zealand
State/province [44] 0 0
Palmerston North
Country [45] 0 0
South Africa
State/province [45] 0 0
Gauteng
Country [46] 0 0
South Africa
State/province [46] 0 0
W Cape
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Sweden
State/province [49] 0 0
Göteborg
Country [50] 0 0
Switzerland
State/province [50] 0 0
Zurich
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Basingstoke
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Cambridge
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Glasgow
Country [54] 0 0
United Kingdom
State/province [54] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bioverativ Therapeutics Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Swedish Orphan Biovitrum
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are: to evaluate the safety and tolerability of rFVIIIFc
administered as a prophylaxis (Arm 1), weekly (Arm 2), on-demand (Arm 3), and surgical
treatment regimen; to evaluate the efficacy of the rFVIIIFc tailored prophylaxis regimen (Arm
1); to evaluate the efficacy of rFVIIIFc administered as an on-demand (Arm 3) and surgical
treatment regimen. The secondary objectives of this study are: to characterize the PK profile
of rFVIIIFc and compare the PK of rFVIIIFc with the currently marketed product, Advate®; to
characterize the range of dose and schedules required to adequately prevent bleeding in a
prophylaxis regimen, maintain hemostasis in a surgical setting, or to treat bleeding episodes
in an on-demand, weekly treatment, or prophylaxis setting.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01181128
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Bioverativ Therapeutics Inc.
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