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

CSL Behring

Status and phase: Completed; Phase 3

Conditions: Severe Hemophilia A; Hemophilia A

Treatments: Biological: rVIII-SingleChain

Study type: Interventional

Funder types: Industry

Identifiers

NCT02172950

2013-003262-13 (EudraCT Number)

CSL627_3001

Details and patient eligibility

About

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.

Enrollment: 246 patients

Sex: Male

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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246 participants in 2 patient groups

Previously treated patients (PTPs)

Experimental group

Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

Treatment:

Biological: rVIII-SingleChain

Previously untreated patients (PUPs)

Experimental group

Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

Treatment:

Biological: rVIII-SingleChain