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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01458106




Registration number
NCT01458106
Ethics application status
Date submitted
20/10/2011
Date registered
24/10/2011
Date last updated
19/12/2020

Titles & IDs
Public title
Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Pediatric Subjects With Hemophilia A
Scientific title
An Open-Label, Multicenter Evaluation of Safety, Pharmacokinetics, and Efficacy of Recombinant Coagulation Factor VIII Fc Fusion Protein, BIIB031, in the Prevention and Treatment of Bleeding Episodes in Pediatric Subjects With Hemophilia A
Secondary ID [1] 0 0
2011-003073-28
Secondary ID [2] 0 0
8HA02PED
Universal Trial Number (UTN)
Trial acronym
Kids ALONG
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: Drugs - BIIB031 (rFVIIIFc)
Treatment: Drugs - FVIII (PK subgroup only)

Experimental: All participants - PK subgroup: After a Washout Period of =72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of =72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.


Treatment: Drugs: BIIB031 (rFVIIIFc)
Vials of rFVIIIFc were combined as needed, based on the actual labeled potency to achieve the participant's calculated dose. Partial vial use was allowed, in order to achieve the calculated dose.

Treatment: Drugs: FVIII (PK subgroup only)
Baseline prestudy FVIII dosing in participants who enter the PK subgroup. Vials of prestudy FVIII were combined as needed, based on the nominal labeled potency (e.g., 250 IU, 500 IU, and 1000 IU), to achieve the participant's calculated dose.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of FVIII Inhibitor Development
Timepoint [1] 0 0
Up to Week 26 +/- 7 days, or up to 50 exposure days (EDs) if reached prior to Week 26
Secondary outcome [1] 0 0
Annualized Bleeding Rate
Timepoint [1] 0 0
Up to Week 26 +/- 7 days (efficacy period as defined in description)
Secondary outcome [2] 0 0
Annualized Joint Bleeding Rate (Spontaneous)
Timepoint [2] 0 0
Up to Week 26 +/- 7 days (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 Week 26 +/- 7 days
Secondary outcome [4] 0 0
Physician's Global Assessment of the Participant's Response to His rFVIIIFc Regimen
Timepoint [4] 0 0
Up to Week 26 +/- 7 days
Secondary outcome [5] 0 0
Annualized rFVIIIFc Consumption Per Participant
Timepoint [5] 0 0
Up to Week 26 +/- 7 days (efficacy period as defined in description)
Secondary outcome [6] 0 0
Number of Days From Last Treatment Injection to a Spontaneous Bleeding Episode
Timepoint [6] 0 0
Up to Week 26 +/- 7 days (efficacy period as defined in description)
Secondary outcome [7] 0 0
Number of Injections Required for Resolution of a Bleeding Episode
Timepoint [7] 0 0
Up to Week 26 +/- 7 days (efficacy period as defined in description)
Secondary outcome [8] 0 0
Total Dose Required for Resolution of a Bleeding Episode
Timepoint [8] 0 0
Up to Week 26 +/- 7 days (efficacy period as defined in description)
Secondary outcome [9] 0 0
Maximum Plasma Activity (Cmax; One-stage Activated Partial Thromboplastin Time [aPTT] Clotting Assay)
Timepoint [9] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [10] 0 0
Maximum Plasma Activity (Cmax; Two-stage Chromogenic Assay)
Timepoint [10] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [11] 0 0
Elimination Half Life (t1/2; One-stage aPTT Clotting Assay)
Timepoint [11] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [12] 0 0
Elimination Half Life (t1/2; Two-stage Chromogenic Assay)
Timepoint [12] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [13] 0 0
Clearance (CL; One-stage aPTT Clotting Assay)
Timepoint [13] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [14] 0 0
Clearance (CL; Two-stage Chromogenic Assay)
Timepoint [14] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [15] 0 0
Volume at Steady State (Vss; One-stage aPTT Clotting Assay)
Timepoint [15] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [16] 0 0
Volume at Steady State (Vss; Two-stage Chromogenic Assay)
Timepoint [16] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [17] 0 0
Dose Normalized Area Under the Curve (DNAUC; One-stage aPTT Clotting Assay)
Timepoint [17] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [18] 0 0
Dose Normalized Area Under the Curve (DNAUC; Two-stage Chromogenic Assay)
Timepoint [18] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [19] 0 0
Mean Residence Time (MRT; One-stage aPTT Clotting Assay)
Timepoint [19] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [20] 0 0
Mean Residence Time (MRT; Two-stage Chromogenic Assay)
Timepoint [20] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [21] 0 0
Incremental Recovery (IR; One-stage aPTT Clotting Assay)
Timepoint [21] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [22] 0 0
Incremental Recovery (IR; Two-stage Chromogenic Assay)
Timepoint [22] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [23] 0 0
Time at Maximum Activity (Tmax; One-stage aPTT Clotting Assay)
Timepoint [23] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [24] 0 0
Time at Maximum Activity (Tmax; Two-stage Chromogenic Assay)
Timepoint [24] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [25] 0 0
Lambda Z (One-stage aPTT Clotting Assay)
Timepoint [25] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [26] 0 0
Lambda Z (Two-stage Chromogenic Assay)
Timepoint [26] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [27] 0 0
Volume at Terminal Phase (Vz; One-stage aPTT Clotting Assay)
Timepoint [27] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [28] 0 0
Volume at Terminal Phase (Vz; Two-stage Chromogenic Assay)
Timepoint [28] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [29] 0 0
Area Under the Curve to the Last Measurable Timepoint (AUClast; One-stage aPTT Clotting Assay)
Timepoint [29] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [30] 0 0
Area Under the Curve to the Last Measurable Timepoint (AUClast; Two-stage Chromogenic Assay)
Timepoint [30] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [31] 0 0
Area Under the Curve to Infinity (AUCinf; One-stage aPTT Clotting Assay)
Timepoint [31] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [32] 0 0
Area Under the Curve to Infinity (AUCinf; Two-stage Chromogenic Assay)
Timepoint [32] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [33] 0 0
Percentage of AUCinf Extrapolated From the Last Data Point to Infinity (%AUCext; One-stage aPTT Clotting Assay)
Timepoint [33] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Secondary outcome [34] 0 0
Percentage of AUCinf Extrapolated From the Last Data Point to Infinity (%AUCext; Two-stage Chromogenic Assay)
Timepoint [34] 0 0
Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Eligibility
Key inclusion criteria
Key

* Severe hemophilia A defined as <1 IU/dL (<1%) endogenous FVIII
* Male <12 years of age and weight =13 kg
* History of at least 50 documented prior exposure days to FVIII
* No current, or history of, inhibitor development to FVIII

Key
Minimum age
No limit
Maximum age
11 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Other coagulation disorders in addition to Hemophilia A
* History of anaphylaxis associated with any FVIII or IV immunoglobulin administration

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
1/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2013
Sample size
Target
Accrual to date
Final
71
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Brisbane
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
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
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
Hong Kong
State/province [10] 0 0
Hong Kong
Country [11] 0 0
Ireland
State/province [11] 0 0
Dublin
Country [12] 0 0
Netherlands
State/province [12] 0 0
Groningen
Country [13] 0 0
Poland
State/province [13] 0 0
Lublin
Country [14] 0 0
South Africa
State/province [14] 0 0
Johannesburg
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Cambridgshire
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Hampshire
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Glasgow
Country [18] 0 0
United Kingdom
State/province [18] 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

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01458106