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

NCT02172950 | Completed Phase 3 Results DMC

• 2 other identifiers: CSL627_30012013-003262-13
• Study Type: interventional
• Target: 246
• Locations: 24 countries
• Sites: 61

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.

Conditions

Hemophilia A; Severe Hemophilia A

Outcome Measures

Primary Outcomes (4)

• 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).

• 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).

• 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

• 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 Outcomes (18)

• Percentage of Bleeding Episodes Treated Successfully in PTPs

  Up to 5 years

• Annualized Bleeding Rate in PTPs and PUPs

  Up to 5 years

• Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs

  Up to 5 years

• Mean Number of On-demand Infusions of CSL627

  Up to 5 years

• Mean On-demand Dose Administered of CSL627

  Up to 5 years

Study Arms (2)

Previously treated patients (PTPs)

EXPERIMENTAL

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.

Biological: rVIII-SingleChain

Previously untreated patients (PUPs)

EXPERIMENTAL

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.

Biological: rVIII-SingleChain

Interventions

rVIII-SingleChain BIOLOGICAL

Recombinant single-chain coagulation factor VIII

Also known as: CSL627

Previously treated patients (PTPs); Previously untreated patients (PUPs)

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (64)

Study Site 8400213

San Diego, California, 92103-8651, United States

Location

Study Site 8400241

Aurora, Colorado, 80045, United States

Location

Study Site 8400118

Hartford, Connecticut, 06106, United States

Location

Study Site 8400116

Miami, Florida, 33136, United States

Location

Study Site 8400184

Chicago, Illinois, 60612, United States

Location

Study Site 8400204

New Orleans, Louisiana, 70112, United States

Location

Study Site 8400240

Dallas, Texas, 75390-9016, United States

Location

Study Site 8400041

Houston, Texas, 77030, United States

Location

Study Site 8400154

Milwaukee, Wisconsin, 53226, United States

Location

Study Site 0360014

Melbourne, 3052, Australia

Location

Study Site 0360028

Nedlands, WA 6009, Australia

Location

Study Site 0360031

Perth, WA 6000, Australia

Location

Study Site 0400012

Graz, 8036, Austria

Location

Study Site 0400003

Linz, 4020, Austria

Location

Study Site 0400001

Vienna, 1090, Austria

Location

Study Site 0400002

Vienna, 1090, Austria

Location

Study Site 1240022

Saint John, E2L 4L2, Canada

Location

Study Site 2030017

Hradec Králové, 500 05, Czechia

Location

Study Site 2500015

Brest, 29609, France

Location

Study Site 2500017

Le Kremlin-Bicêtre, 94270, France

Location

Study Site 2500028

Lille, 59037, France

Location

Study Site 2500018

Nantes, 44093, France

Location

Study Site 2500002

Paris, 75015, France

Location

Study Site 2680001

Tbilisi, 0179, Georgia

Location

Study Site 2760034

Bonn, 53127, Germany

Location

Study Site 2760091

Frankfurt, 60596, Germany

Location

Study Site 2760087

Giessen, 35385, Germany

Location

Study Site 2760066

Hanover, 30625, Germany

Location

Study Site 3480007

Debrecen, 4032, Hungary

Location

Study Site 3720002

Dublin, 12, Ireland

Location

Study Site 3800023

Milan, 20122, Italy

Location

Study Site 3920031

Hyōgo, 663-8501, Japan

Location

Study Site 3920029

Nagoya, 466-8550, Japan

Location

Study Site 3920064

Okayama, 710-8602, Japan

Location

Study Site 3920033

Saitama, 339-8551, Japan

Location

Study Site 3920025

Tokyo, 160-0023, Japan

Location

Study Site 4220007

Beirut, 165191, Lebanon

Location

Study Site 4580001

Kuala Lumpur, 50400, Malaysia

Location

Study Site 5280006

Amsterdam-Zuidoost, 1105 AZ, Netherlands

Location

Study Site 5280008

Nijmegen, 6500, Netherlands

Location

Study Site 5280007

Utrecht, 3584, Netherlands

Location

Study Site 6080001

Cebu City, 6000, Philippines

Location

Study Site 6080002

Davao City, 8000, Philippines

Location

Study Site 6160013

Gdansk, 80-952, Poland

Location

Study Site 6160038

Krakow, 31-531, Poland

Location

Study Site 6160035

Rzeszów, 35-301, Poland

Location

Study Site 6160014

Wroclaw, 50-367, Poland

Location

Study Site 6200001

Porto, 4200-319, Portugal

Location

Study Site 6420030

Bucharest, 011026, Romania

Location

Study Site 6420037

Timișoara, 300011, Romania

Location

Study Site 7100001

Parktown, 2193, South Africa

Location

Study Site 7240008

A Coruña, 15006, Spain

Location

Study Site 7240021

Barcelona, 08035, Spain

Location

Study Site 7240007

Madrid, 28046, Spain

Location

Study Site 7240023

Valencia, 46026, Spain

Location

Study Site 7560010

Lucerne, 6000, Switzerland

Location

Study Site 7640001

Bangkok, 10330, Thailand

Location

Study Site 7640005

Bangkok, 10700, Thailand

Location

Study Site 7640002

Chiang Mai, 50200, Thailand

Location

Study Site 7640004

Khon Kaen, 40002, Thailand

Location

Study Site 7640003

Songkhla, 90110, Thailand

Location

Study Site 8040007

Dnipropetrovsk, 49102, Ukraine

Location

Study Site 8040005

Lviv, 79044, Ukraine

Location

Study Site 8260008

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

use email contact

Study Officials

• Program Director

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2014
• First Posted: June 24, 2014
• Study Start: October 13, 2014
• Primary Completion: January 19, 2021
• Study Completion: January 19, 2021
• Last Updated: October 27, 2021
• Results First Posted: October 27, 2021

Record last verified: 2021-09

Locations

CZ (1); IT (1); HU (1); DE (4); LE (1); FR (5); CA (1); RO (2); ZA (1); ES (4); CH (1); NL (3); TH (5); PH (2); AU (4); PT (1); GE (1); US (9); PL (4); MY (1); IE (1); JP (5); UA (2); GB (1)