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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01486927




Registration number
NCT01486927
Ethics application status
Date submitted
19/11/2011
Date registered
7/12/2011
Date last updated
9/08/2016

Titles & IDs
Public title
An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A
Scientific title
A Phase I/III Open-label, Multicenter, Crossover Safety, Efficacy and Pharmacokinetic Study of Recombinant Coagulation Factor VIII (rFVIII) Compared to Recombinant Human Antihaemophilic Factor VIII (rFVIII; INN: Octocog Alfa) in Subjects With Hemophilia A, and a Repeat PK, Safety and Efficacy Study
Secondary ID [1] 0 0
2011-002393-23
Secondary ID [2] 0 0
CSL627_1001
Universal Trial Number (UTN)
Trial acronym
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
Other interventions - rVIII-SingleChain
Other interventions - Octocog alfa

Experimental: Recombinant Factor VIII (rFVIII) -


Other interventions: rVIII-SingleChain
In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.

Other interventions: Octocog alfa
In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg of octocog alfa preceded by a 4-day washout period. Octocog alfa is the international nonproprietary name (INN) for recombinant human coagulation factor VIII.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment Success - The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.
Timepoint [1] 0 0
Up to 24 months
Primary outcome [2] 0 0
Inhibitor Formation to FVIII - Number of subjects who develop inhibitors to FVIII
Timepoint [2] 0 0
Up to 24 months
Primary outcome [3] 0 0
Annualized Spontaneous Bleeding Rate - The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).
Timepoint [3] 0 0
Up to 24 months
Primary outcome [4] 0 0
Treatment Success During the Peri-operative Surgical Sub-study - Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.
Timepoint [4] 0 0
From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Secondary outcome [1] 0 0
AUC0-8 (Part 1) - AUC0-8 (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Timepoint [1] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion
Secondary outcome [2] 0 0
Cmax (Part 1) - Cmax of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Timepoint [2] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion
Secondary outcome [3] 0 0
Tmax (Part 1) - Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after a single infusion of octocog alfa and rVIII-SingleChain.
Timepoint [3] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion
Secondary outcome [4] 0 0
Half-life (t1/2) (Part 1) - Half-life (t1/2) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Timepoint [4] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion.
Secondary outcome [5] 0 0
Mean Residence Time (MRT) (Part 1) - Mean residence time (MRT) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Timepoint [5] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion
Secondary outcome [6] 0 0
Clearance (Cl) (Part 1) - Clearance (Cl) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Timepoint [6] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion
Secondary outcome [7] 0 0
Volume of Distribution at Steady-state (Vss) (Part 1) - Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Timepoint [7] 0 0
Before infusion and at up to 10 time points within 72 hours of infusion
Secondary outcome [8] 0 0
Incremental Recovery (Part 1) - Incremental recovery of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Timepoint [8] 0 0
At 30 minutes after infusion
Secondary outcome [9] 0 0
Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds - The annualized bleeding rate was derived for each subject as follows: 365.25*(number of bleeding episodes requiring treatment) / (observed treatment period of interest).
Timepoint [9] 0 0
Up to 24 months
Secondary outcome [10] 0 0
Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis - Percentage of bleeding episodes requiring 1, 2, 3 or > 3 infusions of rVIII-SingleChain to achieve hemostasis. The denominator includes all treated bleeding episodes.
Timepoint [10] 0 0
During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)

Eligibility
Key inclusion criteria
- Diagnosis of severe hemophilia A defined as <1% FVIII:C documented in medical records.

- Males between 18 and 65 years of age (Parts 1 and 2).

- Males between 12 and 65 years of age (Part 3).

- Subjects who have received or are currently receiving FVIII products (plasma-derived
and/or recombinant FVIII) and have had >150 exposure days (EDs) with a FVIII product

- Written informed consent for study participation obtained before undergoing any study
specific procedures.
Minimum age
12 Years
Maximum age
65 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Any history of or current FVIII inhibitors

- Any first order family history of FVIII inhibitors

- Use of an Investigational Medicinal Product within 30 days prior to the first
rVIII-SingleChain administration.

- Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to
administration of rVIII-SingleChain or reference product.

- Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or
hamster protein.

- Any known congenital or acquired coagulation disorder other than congenital FVIII
deficiency.

- Platelet count < 100,000/µL at screening.

- Human immunodeficiency virus (HIV) positive subjects with a CD4 count < 200/mm3, in
their medical history or at screening if available results are older than one year.
(HIV positive subjects may participate in the study and antiviral therapy are
permitted, at the discretion of the Investigator).

- Subject currently receiving IV immunomodulating agents such as immunoglobulin or
chronic systemic corticosteroid treatment.

- Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase
(ALT) values > 5 times (x) the upper limit of normal (ULN) at Screening.

- Subjects with serum creatinine values > 2 x ULN at Screening.

- Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism,
myocardial infarction and arterial embolus within 3 months prior to Day 1.

- Experienced life-threatening bleeding episode or had major surgery or an orthopedic
surgical procedure during the 3 months prior to Day 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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 2/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)
Recruitment hospital [1] 0 0
Study Site - Nedlands
Recruitment hospital [2] 0 0
Study Site - Perth
Recruitment postcode(s) [1] 0 0
WA 6009 - Nedlands
Recruitment postcode(s) [2] 0 0
WA 6000 - Perth
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
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Austria
State/province [9] 0 0
Graz
Country [10] 0 0
Austria
State/province [10] 0 0
Vienna
Country [11] 0 0
Canada
State/province [11] 0 0
New Brunswick
Country [12] 0 0
Czech Republic
State/province [12] 0 0
Hradec Králové
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Bonn
Country [15] 0 0
Germany
State/province [15] 0 0
Gießen
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Germany
State/province [17] 0 0
Hannover
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Hungary
State/province [19] 0 0
Debrecen
Country [20] 0 0
Italy
State/province [20] 0 0
Florence
Country [21] 0 0
Italy
State/province [21] 0 0
Milan
Country [22] 0 0
Italy
State/province [22] 0 0
Padova
Country [23] 0 0
Italy
State/province [23] 0 0
Torino
Country [24] 0 0
Japan
State/province [24] 0 0
Kashihara, Nara
Country [25] 0 0
Japan
State/province [25] 0 0
Kitakyushu, Fukuoka
Country [26] 0 0
Japan
State/province [26] 0 0
Nagoya
Country [27] 0 0
Japan
State/province [27] 0 0
Nishinomiya, Hyogo
Country [28] 0 0
Japan
State/province [28] 0 0
Okayama
Country [29] 0 0
Japan
State/province [29] 0 0
Saitama
Country [30] 0 0
Japan
State/province [30] 0 0
Suginami-ku, Tokyo
Country [31] 0 0
Japan
State/province [31] 0 0
Tokyo
Country [32] 0 0
Lebanon
State/province [32] 0 0
Beirut
Country [33] 0 0
Malaysia
State/province [33] 0 0
Kuala Lumpur
Country [34] 0 0
Netherlands
State/province [34] 0 0
Utrecht
Country [35] 0 0
Philippines
State/province [35] 0 0
Cebu City
Country [36] 0 0
Philippines
State/province [36] 0 0
Davao City
Country [37] 0 0
Poland
State/province [37] 0 0
Silesia
Country [38] 0 0
Poland
State/province [38] 0 0
Gdansk
Country [39] 0 0
Poland
State/province [39] 0 0
Krakow
Country [40] 0 0
Romania
State/province [40] 0 0
Bucharest
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Barnaul
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Kemerovo
Country [43] 0 0
South Africa
State/province [43] 0 0
Cape Town
Country [44] 0 0
South Africa
State/province [44] 0 0
Johannesburg
Country [45] 0 0
Spain
State/province [45] 0 0
Barcelona
Country [46] 0 0
Spain
State/province [46] 0 0
La Coruna
Country [47] 0 0
Spain
State/province [47] 0 0
Valencia
Country [48] 0 0
Ukraine
State/province [48] 0 0
Dnipropetrovsk
Country [49] 0 0
Ukraine
State/province [49] 0 0
Donetsk
Country [50] 0 0
Ukraine
State/province [50] 0 0
Lviv
Country [51] 0 0
United Kingdom
State/province [51] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, non-randomized, efficacy, safety and pharmacokinetic (PK) study
comparing octocog alfa and rVIII-SingleChain. The study consists of three parts, a PK period
(Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety,
efficacy, and repeat PK period (Part 3) and also includes a surgical sub-study for subjects
enrolled in Parts 2 and 3.
Trial website
https://clinicaltrials.gov/show/NCT01486927
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Program Director
Address 0 0
CSL Behring
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

Summary results
Other publications