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Trial details imported from ClinicalTrials.gov

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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents