Clinical trial NCT01486927: An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hemophilia A
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2011-12-07
Enrollment: 175
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Treatment Success
timeFrame: Up to 24 months
measure: Inhibitor Formation to FVIII
timeFrame: Up to 24 months
measure: Annualized Spontaneous Bleeding Rate
timeFrame: Up to 24 months
measure: Treatment Success During the Peri-operative Surgical Sub-study
timeFrame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Secondary outcomes:
measure: AUC0-∞ (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion
measure: Cmax (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion
measure: Tmax (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion
measure: Half-life (t1/2) (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion.
measure: Mean Residence Time (MRT) (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion
measure: Clearance (Cl) (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion
measure: Volume of Distribution at Steady-state (Vss) (Part 1)
timeFrame: Before infusion and at up to 10 time points within 72 hours of infusion
measure: Incremental Recovery (Part 1)
timeFrame: At 30 minutes after infusion
measure: Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds
timeFrame: Up to 24 months
measure: Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis
timeFrame: During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)
Other outcomes:
measure: Incremental Recovery (Part 3)
timeFrame: At 30 minutes after infusion
measure: Volume of Distribution at Steady-state (Vss) (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion.
measure: Clearance (Cl) (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion.
measure: Mean Residence Time (MRT) (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion.
measure: Half-life (t1/2) (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion.
measure: Tmax (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion.
measure: Cmax (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion
measure: AUC0-∞ (Part 3)
timeFrame: Before infusion and at up to 12 time points within 96 hours of infusion
Locations:
city: Sacramento
country: United States
facility: Study Site
state: California
city: San Diego
country: United States
facility: Study Site
state: California
city: Aurora
country: United States
facility: Study Site
state: Colorado
city: Hartford
country: United States
facility: Study Site
state: Connecticut
city: Miami
country: United States
facility: Study Site
state: Florida
city: Chicago
country: United States
facility: Study Site
state: Illinois
city: New Orleans
country: United States
facility: Study Site
state: Louisiana
city: Houston
country: United States
facility: Study Site
state: Texas
city: Milwaukee
country: United States
facility: Study Site
state: Wisconsin
city: Nedlands
country: Australia
facility: Study Site
city: Perth
country: Australia
facility: Study Site
city: Graz
country: Austria
facility: Study Site
city: Vienna
country: Austria
facility: Study Site
city: New Brunswick
country: Canada
facility: Study Site
city: Hradec Králové
country: Czech Republic
facility: Study Site
city: Berlin
country: Germany
facility: Study Site
city: Berlin
country: Germany
facility: Study Site
city: Bonn
country: Germany
facility: Study Site
city: Gießen
country: Germany
facility: Study Site
city: Hamburg
country: Germany
facility: Study Site
city: Hannover
country: Germany
facility: Study Site
city: Heidelberg
country: Germany
facility: Study Site
city: Debrecen
country: Hungary
facility: Study Site
city: Florence
country: Italy
facility: Study Site
city: Milan
country: Italy
facility: Study Site
city: Padova
country: Italy
facility: Study Site
city: Padova
country: Italy
facility: Study Site
city: Torino
country: Italy
facility: Study Site
city: Kashihara, Nara
country: Japan
facility: Study Site
city: Kitakyushu, Fukuoka
country: Japan
facility: Study Site
city: Nagoya
country: Japan
facility: Study Site
city: Nishinomiya, Hyogo
country: Japan
facility: Study Site
city: Okayama
country: Japan
facility: Study Site
city: Saitama
country: Japan
facility: Study Site
city: Suginami-ku, Tokyo
country: Japan
facility: Study Site
city: Tokyo
country: Japan
facility: Study Site
city: Beirut
country: Lebanon
facility: Study Site
city: Kuala Lumpur
country: Malaysia
facility: Study Site
city: Utrecht
country: Netherlands
facility: Study Site
city: Cebu City
country: Philippines
facility: Study Site
city: Davao City
country: Philippines
facility: Study Site
city: Wroclaw
country: Poland
facility: Study Site
state: Silesia
city: Gdansk
country: Poland
facility: Study Site
city: Krakow
country: Poland
facility: Study Site
city: Bucharest
country: Romania
facility: Study Site
city: Barnaul
country: Russian Federation
facility: Study Site
city: Kemerovo
country: Russian Federation
facility: Study Site
city: Cape Town
country: South Africa
facility: Study Site
city: Johannesburg
country: South Africa
facility: Study Site
city: Barcelona
country: Spain
facility: Study Site
city: La Coruna
country: Spain
facility: Study Site
city: Valencia
country: Spain
facility: Study Site
city: Dnipropetrovsk
country: Ukraine
facility: Study Site
city: Donetsk
country: Ukraine
facility: Study Site
city: Lviv
country: Ukraine
facility: Study Site
city: London
country: United Kingdom
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Program Director
role: STUDY_DIRECTOR
References:
citation: Mahlangu J, Kuliczkowski K, Karim FA, Stasyshyn O, Kosinova MV, Lepatan LM, Skotnicki A, Boggio LN, Klamroth R, Oldenburg J, Hellmann A, Santagostino E, Baker RI, Fischer K, Gill JC, P'Ng S, Chowdary P, Escobar MA, Khayat CD, Rusen L, Bensen-Kennedy D, Blackman N, Limsakun T, Veldman A, St Ledger K, Pabinger I; AFFINITY Investigators. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood. 2016 Aug 4;128(5):630-7. doi: 10.1182/blood-2016-01-687434. Epub 2016 Jun 21.