An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02172950
• Other study ID #: CSL627_3001
• Secondary ID: 2013-003262-13
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2014
• Est. completion date: January 19, 2021

Study information

• Verified date: September 2021
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: January 19, 2021
• Est. primary completion date: January 19, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Biological:
• rVIII-SingleChain
Recombinant single-chain coagulation factor VIII

Locations

Country	Name	City	State
Australia	Study Site 0360014	Melbourne
Australia	Study Site 0360028	Nedlands
Australia	Study Site 0360031	Perth
Austria	Study Site 0400012	Graz
Austria	Study Site 0400003	Linz
Austria	Study Site 0400001	Wien
Austria	Study Site 0400002	Wien
Canada	Study Site 1240022	Saint John
Czechia	Study Site 2030017	Hradec Kralove
France	Study Site 2500015	Brest
France	Study Site 2500017	Le Kremlin Bicetre
France	Study Site 2500028	Lille Cedex
France	Study Site 2500018	Nantes
France	Study Site 2500002	Paris
Georgia	Study Site 2680001	Tbilisi
Germany	Study Site 2760034	Bonn
Germany	Study Site 2760091	Frankfurt
Germany	Study Site 2760087	Giessen
Germany	Study Site 2760066	Hannover
Hungary	Study Site 3480007	Debrecen
Ireland	Study Site 3720002	Dublin
Italy	Study Site 3800023	Milano
Japan	Study Site 3920031	Hyogo
Japan	Study Site 3920029	Nagoya
Japan	Study Site 3920064	Okayama
Japan	Study Site 3920033	Saitama
Japan	Study Site 3920025	Tokyo
Lebanon	Study Site 4220007	Beirut
Malaysia	Study Site 4580001	Kuala Lumpur
Netherlands	Study Site 5280006	Amsterdam Zuidoost
Netherlands	Study Site 5280008	Nijmegen
Netherlands	Study Site 5280007	Utrecht
Philippines	Study Site 6080001	Cebu City
Philippines	Study Site 6080002	Davao City
Poland	Study Site 6160013	Gdansk
Poland	Study Site 6160038	Krakow
Poland	Study Site 6160035	Rzeszow
Poland	Study Site 6160014	Wroclaw
Portugal	Study Site 6200001	Porto
Romania	Study Site 6420030	Bucharest
Romania	Study Site 6420037	Timisoara
South Africa	Study Site 7100001	Parktown
Spain	Study Site 7240008	A Coruna
Spain	Study Site 7240021	Barcelona
Spain	Study Site 7240007	Madrid
Spain	Study Site 7240023	Valencia
Switzerland	Study Site 7560010	Luzern
Thailand	Study Site 7640001	Bangkok
Thailand	Study Site 7640005	Bangkok
Thailand	Study Site 7640002	Chiang Mai
Thailand	Study Site 7640004	Khon Kaen
Thailand	Study Site 7640003	Songkhla
Ukraine	Study Site 8040007	Dnipropetrovsk
Ukraine	Study Site 8040005	Lviv
United Kingdom	Study Site 8260008	London
United States	Study Site 8400241	Aurora	Colorado
United States	Study Site 8400184	Chicago	Illinois
United States	Study Site 8400240	Dallas	Texas
United States	Study Site 8400118	Hartford	Connecticut
United States	Study Site 8400041	Houston	Texas
United States	Study Site 8400116	Miami	Florida
United States	Study Site 8400154	Milwaukee	Wisconsin
United States	Study Site 8400204	New Orleans	Louisiana
United States	Study Site 8400213	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czechia,  France,  Georgia,  Germany,  Hungary,  Ireland,  Italy,  Japan,  Lebanon,  Malaysia,  Netherlands,  Philippines,  Poland,  Portugal,  Romania,  South Africa,  Spain,  Switzerland,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627		At the closest visit after 100 EDs (up to 5 years).
Primary	Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627	High-titer inhibitor is defined as an inhibitor titer of = 5 Bethesda units/mL.	At the closest visit after 50 EDs (up to 5 years).
Primary	Percent Treatment Success for Major Bleeding Episodes in PUPs	Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.	Up to 5 years
Primary	Annualized Spontaneous Bleeding Rate in PUPs	The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.	Up to 5 years
Secondary	Percentage of Bleeding Episodes Treated Successfully in PTPs	Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response".	Up to 5 years
Secondary	Annualized Bleeding Rate in PTPs and PUPs	The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens	Up to 5 years
Secondary	Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs		Up to 5 years
Secondary	Mean Number of On-demand Infusions of CSL627		Up to 5 years
Secondary	Mean On-demand Dose Administered of CSL627		Up to 5 years
Secondary	Mean Prophylaxis Dose Administered of CSL627		Up to 5 years
Secondary	Mean Total Amount of CSL627 Administered During Surgery Period in PTPs		Day of surgery up to 336 hours post-surgery
Secondary	Total Amount of CSL627 Administered During Surgery Period in PUPs		Day of surgery up to 336 hours post-surgery
Secondary	Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery	The investigator will rate the efficacy of the rVIII-SingleChain treatment during surgery based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or poor/no response".	From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Secondary	Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs		Up to 5 years
Secondary	Percentage of PTPs and PUPs Developing Antibodies Against CSL627		PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Secondary	Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins		PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Secondary	Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627	High-titer inhibitor is defined as an inhibitor titer of = 5 Bethesda units/mL.	At the closest visit after 10 EDs (up to 5 years)
Secondary	Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627	Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL.	At the closest visit after 10 and after 50 EDs (up to 5 years)
Secondary	Incidence of Total Inhibitor Formation to FVIII in PUPs		Up to 5 years
Secondary	Percent Treatment Success for Non-major Bleeding Episodes in PUPs	Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Non-major bleeding episodes are those not requiring treatment at the hemophilia center or not threatening subject's life or loss of limb.	Up to 5 years
Secondary	Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627	Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.	Up to 6 hours after first infusion
Secondary	Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values	Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.	Up to 5 years