An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01486927
• Other study ID #: CSL627_1001
• Secondary ID: 2011-002393-23
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 19, 2011
• Last updated: December 11, 2015
• Start date: February 2012
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Paul-Ehrlich-InstitutAustria: Agency for Health and Food SafetyAustria: Federal Office for Safety in Health CareSweden: Medical Products AgencyItaly: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Poland: Ministry of HealthRussia: Ministry of Health of the Russian FederationJapan: Pharmaceuticals and Medical Devices AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySpain: Spanish Agency of MedicinesHungary: National Institute for Quality and Organizational Development in Healthcare and MedicinesCzech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

This is an open-label, non-randomized, efficacy, safety and PK study comparing octocog alfa and CSL627. 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 section (Part 3) including a surgical sub-study for subjects enrolled in Parts 2 and 3.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

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 CSL627 administration.

• Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of CSL627 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.

• 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Biological:
• Recombinant Factor VIII (rFVIII)
In Part 1 of the study, subjects will receive a single infusion of 50 IU/kg of octocog alfa followed by a single infusion of 50 IU/kg CSL627; each infusion will be preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects will receive infusions of CSL627 to prevent or treat bleeding episodes, at a dose and frequency determined by their study doctor (based on the subject's underlying bleeding phenotype).

Locations

Country	Name	City	State
Australia	Study Site	Nedlands
Australia	Study Site	Perth
Austria	Study Site	Graz
Austria	Study Site	Vienna
Canada	Study Site	New Brunswick
Czech Republic	Study Site	Hradec Králové
Germany	Study Site	Berlin
Germany	Study Site	Berlin
Germany	Study Site	Bonn
Germany	Study Site	Duisburg
Germany	Study Site	Erlangen
Germany	Study Site	Gießen
Germany	Study Site	Hamburg
Germany	Study Site	Hannover
Germany	Study Site	Heidelberg
Germany	Study Site	Münster
Hungary	Study Site	Debrecen
Italy	Study Site	Florence
Italy	Study Site	Milan
Italy	Study Site	Padova
Italy	Study Site	Torino
Japan	Study Site	Kashihara
Japan	Study Site	Kitakyushu
Japan	Study Site	Kitakyushu
Japan	Study Site	Nagoya
Japan	Study Site	Nishinomiya
Japan	Study Site	Okayama
Japan	Study Site	Saitama
Japan	Study Site	Shizuoka
Japan	Study Site	Suginami-ku
Japan	Study Site	Tokyo
Lebanon	Study Site	Beirut
Malaysia	Study Site	Kuala Lumpur
Netherlands	Study Site	Utrecht
Philippines	Study Site	Cebu City
Philippines	Study Site	Davao City
Poland	Study Site	Gdansk
Poland	Study Site	Krakow
Poland	Study Site	Rzeszow
Poland	Study Site	Wroclaw
Poland	Study Site	Wroclaw	Silesia
Romania	Study Site	Bucharest
Romania	Study Site	Bucharest
Russian Federation	Study Site	Kemerovo
Russian Federation	Study Site	Kirov
South Africa	Study Site	Cape Town
South Africa	Study Site	Johannesburg
Spain	Study Site	Barcelona
Spain	Study Site	La Coruna
Spain	Study Site	Madrid
Spain	Study Site	Valencia
Sweden	Study Site	Malmoe
Ukraine	Study Site	Donetsk
Ukraine	Study Site	Lviv
United Kingdom	Study Site	London
United States	Study Site	Aurora	Colorado
United States	Study Site	Chicago	Illinois
United States	Study Site	Dallas	Texas
United States	Study Site	Hartford	Connecticut
United States	Study Site	Houston	Texas
United States	Study Site	Las Vegas	Nevada
United States	Study Site	Miami	Florida
United States	Study Site	Milwaukee	Wisconsin
United States	Study Site	New Orleans	Louisiana
United States	Study Site	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czech Republic,  Germany,  Hungary,  Italy,  Japan,  Lebanon,  Malaysia,  Netherlands,  Philippines,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment success	Subjects will receive treatment for any bleeding episode and the investigator will rate the efficacy of the treatment based on a four point rating scale "excellent, good, moderate or poor/no response".	Up to 24 months	No
Primary	Treatment success during the peri-operative surgical sub-study	Subjects will receive pre-treatment with rFVIII prior to major surgery. The investigator will rate the efficacy of the treatment based on a 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)	No
Primary	Inhibitor formation to FVIII	Number of subjects who develop inhibitors to FVIII	Up to 24 months	No
Primary	Annualized spontaneous bleeding rate	The annualized bleeding rate for subjects taking the prophylaxis treatment regimen	Up to 24 months	No
Secondary	AUC0-t	AUC0-t of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	AUC0-8	AUC0-8 of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Percent of area extrapolated	Percent of area extrapolated of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Cmax	Cmax of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Tmax	Tmax of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Elimination constant	Elimination constant of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Half-life (t1/2)	Half-life (t1/2) of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	AUMC0-8	AUMC0-8 of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Mean residence time (MRT)	Mean residence time (MRT) of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Clearance (Cl)	Clearance (Cl) of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Volume of distribution at steady-state (Vss)	Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and CSL627	Before infusion and at up to 12 time points within 5 days of infusion	No
Secondary	Proportion of bleeding episodes	Proportion of bleeding episodes requiring one, 2, 3 or > 3 infusions of CSL627 to achieve hemostasis	Assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 visit	No
Secondary	Incremental recovery	Incremental recovery of a single infusion of octocog alfa and CSL627	At 30 minutes after infusion	No
Secondary	Annualized bleeding rate for total bleeds, traumatic bleeds, and joint bleeds	The annualized bleeding rate of total bleeds, traumatic bleeds and joint bleeds, for subjects taking the prophylaxis treatment regimen	Up to 24 months	No