Clinical trial NCT02172950: An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A
Official title: A Phase III Open Label, Multicenter, Extension Study to Assess the Safety and Efficacy of Recombinant Coagulation Factor VIII (rVIII-SingleChain, CSL627) in Subjects With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Severe Hemophilia A
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 246
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter, open-label, phase 3 extension study will investigate the safety and efficacy of rVIII-SingleChain for prophylaxis and on-demand treatment of bleeding episodes in at least 200 previously treated patients (PTPs) with severe congenital hemophilia A and previous exposure to FVIII products who achieve at least 100 exposure days (EDs) to rVIII-SingleChain in this study, as well as in previously untreated patients (PUPs) with no previous exposure to any FVIII product who achieve at least 50 EDs to rVIII-SingleChain in this study. A substudy (open to both PTPs and PUPs) will investigate the use of rVIII-SingleChain in surgery. A substudy (open to PUPs who develop an inhibitor to rVIII-SingleChain) will investigate the use of rVIII-SingleChain in immune tolerance induction (ITI) therapy.


Eligibility criteria: Inclusion Criteria:

PTPs:

* Males of any age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels \< 1%) and who participated in a previous CSL-sponsored clinical study with rVIII-SingleChain.
* Males 0 to \<65 years age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels \< 1%), who have at least 50 EDs to any FVIII product, and who are not currently enrolled in a CSL-sponsored clinical study with rVIII-SingleChain.

PUPs:

* Males 0 to \<18 years of who have been diagnosed with severe congenital hemophilia A (FVIII activity levels \< 1%)
* No prior exposure to any Factor VIII product (with the exception of short-term use of blood products).

ITI substudy:

* PUPs who have developed a confirmed inhibitor to rVIII-SingleChain in the main study.

Exclusion Criteria:

* Known or suspected hypersensitivity to rVIII-SingleChain or to any excipients of rVIII-SingleChain or Chinese hamster ovary (CHO) proteins.
* Currently receiving a therapy not permitted during the study.
* Serum creatinine \> 2 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase \> 5 x upper limit of normal at Screening (if specified)
* Any first-order family (eg, siblings) history of FVIII inhibitors
* For PTPs not rolling over directly from a CSL-sponsored clinical study with rVIII-SingleChain: any history of or current FVIII inhibitors

Primary outcomes:
measure: Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627
timeFrame: At the closest visit after 100 EDs (up to 5 years).
measure: Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627
timeFrame: At the closest visit after 50 EDs (up to 5 years).
measure: Percent Treatment Success for Major Bleeding Episodes in PUPs
timeFrame: Up to 5 years
measure: Annualized Spontaneous Bleeding Rate in PUPs
timeFrame: Up to 5 years
Secondary outcomes:
measure: Percentage of Bleeding Episodes Treated Successfully in PTPs
timeFrame: Up to 5 years
measure: Annualized Bleeding Rate in PTPs and PUPs
timeFrame: Up to 5 years
measure: Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs
timeFrame: Up to 5 years
measure: Mean Number of On-demand Infusions of CSL627
timeFrame: Up to 5 years
measure: Mean On-demand Dose Administered of CSL627
timeFrame: Up to 5 years
measure: Mean Prophylaxis Dose Administered of CSL627
timeFrame: Up to 5 years
measure: Mean Total Amount of CSL627 Administered During Surgery Period in PTPs
timeFrame: Day of surgery up to 336 hours post-surgery
measure: Total Amount of CSL627 Administered During Surgery Period in PUPs
timeFrame: Day of surgery up to 336 hours post-surgery
measure: Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery
timeFrame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
measure: Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs
timeFrame: Up to 5 years
measure: Percentage of PTPs and PUPs Developing Antibodies Against CSL627
timeFrame: PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
measure: Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins
timeFrame: PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
measure: Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627
timeFrame: At the closest visit after 10 EDs (up to 5 years)
measure: Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627
timeFrame: At the closest visit after 10 and after 50 EDs (up to 5 years)
measure: Incidence of Total Inhibitor Formation to FVIII in PUPs
timeFrame: Up to 5 years
measure: Percent Treatment Success for Non-major Bleeding Episodes in PUPs
timeFrame: Up to 5 years
measure: Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627
timeFrame: Up to 6 hours after first infusion
measure: Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Study Site 8400213
state: California
city: Aurora
country: United States
facility: Study Site 8400241
state: Colorado
city: Hartford
country: United States
facility: Study Site 8400118
state: Connecticut
city: Miami
country: United States
facility: Study Site 8400116
state: Florida
city: Chicago
country: United States
facility: Study Site 8400184
state: Illinois
city: New Orleans
country: United States
facility: Study Site 8400204
state: Louisiana
city: Dallas
country: United States
facility: Study Site 8400240
state: Texas
city: Houston
country: United States
facility: Study Site 8400041
state: Texas
city: Milwaukee
country: United States
facility: Study Site 8400154
state: Wisconsin
city: Melbourne
country: Australia
facility: Study Site 0360014
city: Nedlands
country: Australia
facility: Study Site 0360028
city: Perth
country: Australia
facility: Study Site 0360031
city: Graz
country: Austria
facility: Study Site 0400012
city: Linz
country: Austria
facility: Study Site 0400003
city: Wien
country: Austria
facility: Study Site 0400001
city: Wien
country: Austria
facility: Study Site 0400002
city: Saint John
country: Canada
facility: Study Site 1240022
city: Hradec Kralove
country: Czechia
facility: Study Site 2030017
city: Brest
country: France
facility: Study Site 2500015
city: Le Kremlin Bicetre
country: France
facility: Study Site 2500017
city: Lille Cedex
country: France
facility: Study Site 2500028
city: Nantes
country: France
facility: Study Site 2500018
city: Paris
country: France
facility: Study Site 2500002
city: Tbilisi
country: Georgia
facility: Study Site 2680001
city: Bonn
country: Germany
facility: Study Site 2760034
city: Frankfurt
country: Germany
facility: Study Site 2760091
city: Giessen
country: Germany
facility: Study Site 2760087
city: Hannover
country: Germany
facility: Study Site 2760066
city: Debrecen
country: Hungary
facility: Study Site 3480007
city: Dublin
country: Ireland
facility: Study Site 3720002
city: Milano
country: Italy
facility: Study Site 3800023
city: Hyogo
country: Japan
facility: Study Site 3920031
city: Nagoya
country: Japan
facility: Study Site 3920029
city: Okayama
country: Japan
facility: Study Site 3920064
city: Saitama
country: Japan
facility: Study Site 3920033
city: Tokyo
country: Japan
facility: Study Site 3920025
city: Beirut
country: Lebanon
facility: Study Site 4220007
city: Kuala Lumpur
country: Malaysia
facility: Study Site 4580001
city: Amsterdam Zuidoost
country: Netherlands
facility: Study Site 5280006
city: Nijmegen
country: Netherlands
facility: Study Site 5280008
city: Utrecht
country: Netherlands
facility: Study Site 5280007
city: Cebu City
country: Philippines
facility: Study Site 6080001
city: Davao City
country: Philippines
facility: Study Site 6080002
city: Gdansk
country: Poland
facility: Study Site 6160013
city: Krakow
country: Poland
facility: Study Site 6160038
city: Rzeszow
country: Poland
facility: Study Site 6160035
city: Wroclaw
country: Poland
facility: Study Site 6160014
city: Porto
country: Portugal
facility: Study Site 6200001
city: Bucharest
country: Romania
facility: Study Site 6420030
city: Timisoara
country: Romania
facility: Study Site 6420037
city: Parktown
country: South Africa
facility: Study Site 7100001
city: A Coruna
country: Spain
facility: Study Site 7240008
city: Barcelona
country: Spain
facility: Study Site 7240021
city: Madrid
country: Spain
facility: Study Site 7240007
city: Valencia
country: Spain
facility: Study Site 7240023
city: Luzern
country: Switzerland
facility: Study Site 7560010
city: Bangkok
country: Thailand
facility: Study Site 7640001
city: Bangkok
country: Thailand
facility: Study Site 7640005
city: Chiang Mai
country: Thailand
facility: Study Site 7640002
city: Khon Kaen
country: Thailand
facility: Study Site 7640004
city: Songkhla
country: Thailand
facility: Study Site 7640003
city: Dnipropetrovsk
country: Ukraine
facility: Study Site 8040007
city: Lviv
country: Ukraine
facility: Study Site 8040005
city: London
country: United Kingdom
facility: Study Site 8260008
Study officials:
affiliation: CSL Behring
name: Program Director
role: STUDY_DIRECTOR
References: