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

NCT ID: NCT01486927

Last Updated: 2016-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-12-31

Brief Summary

This is an open-label, non-randomized, efficacy, safety and pharmacokinetic (PK) study comparing octocog alfa and rVIII-SingleChain. 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 period (Part 3) and also includes a surgical sub-study for subjects enrolled in Parts 2 and 3.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Recombinant Factor VIII (rFVIII)

Group Type: EXPERIMENTAL

rVIII-SingleChain

Intervention Type: BIOLOGICAL

In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.

Octocog alfa

Intervention Type: BIOLOGICAL

In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg of octocog alfa preceded by a 4-day washout period. Octocog alfa is the international nonproprietary name (INN) for recombinant human coagulation factor VIII.

Interventions

rVIII-SingleChain

In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.

Intervention Type: BIOLOGICAL

Octocog alfa

In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg of octocog alfa preceded by a 4-day washout period. Octocog alfa is the international nonproprietary name (INN) for recombinant human coagulation factor VIII.

Intervention Type: BIOLOGICAL

Other Intervention Names

Recombinant Factor VIII (rFVIII); CSL627; Human coagulation factor VIII (rDNA)

Eligibility Criteria

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 rVIII-SingleChain administration.
• Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain 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.
• Human immunodeficiency virus (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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Program Director

Role: STUDY_DIRECTOR

CSL Behring

Locations

Study Site

Sacramento, California, United States

Study Site

San Diego, California, United States

Study Site

Aurora, Colorado, United States

Study Site

Hartford, Connecticut, United States

Study Site

Miami, Florida, United States

Study Site

Chicago, Illinois, United States

Study Site

New Orleans, Louisiana, United States

Study Site

Houston, Texas, United States

Study Site

Milwaukee, Wisconsin, United States

Study Site

Nedlands, , Australia

Study Site

Perth, , Australia

Study Site

Graz, , Austria

Study Site

Vienna, , Austria

Study Site

New Brunswick, , Canada

Study Site

Hradec Králové, , Czechia

Study Site

Berlin, , Germany

Study Site

Berlin, , Germany

Study Site

Bonn, , Germany

Study Site

Giessen, , Germany

Study Site

Hamburg, , Germany

Study Site

Hanover, , Germany

Study Site

Heidelberg, , Germany

Study Site

Debrecen, , Hungary

Study Site

Florence, , Italy

Study Site

Milan, , Italy

Study Site

Padua, , Italy

Study Site

Padua, , Italy

Study Site

Torino, , Italy

Study Site

Kashihara, Nara, , Japan

Study Site

Kitakyushu, Fukuoka, , Japan

Study Site

Nagoya, , Japan

Study Site

Nishinomiya, Hyogo, , Japan

Study Site

Okayama, , Japan

Study Site

Saitama, , Japan

Study Site

Suginami-ku, Tokyo, , Japan

Study Site

Tokyo, , Japan

Study Site

Beirut, , Lebanon

Study Site

Kuala Lumpur, , Malaysia

Study Site

Utrecht, , Netherlands

Study Site

Cebu City, , Philippines

Study Site

Davao City, , Philippines

Study Site

Wroclaw, Silesian Voivodeship, Poland

Study Site

Gdansk, , Poland

Study Site

Krakow, , Poland

Study Site

Bucharest, , Romania

Study Site

Barnaul, , Russia

Study Site

Kemerovo, , Russia

Study Site

Cape Town, , South Africa

Study Site

Johannesburg, , South Africa

Study Site

A Coruña, , Spain

Study Site

Barcelona, , Spain

Study Site

Valencia, , Spain

Study Site

Dnipropetrovsk, , Ukraine

Study Site

Donetsk, , Ukraine

Study Site

Lviv, , Ukraine

Study Site

London, , United Kingdom

Countries

United States; Australia; Austria; Canada; Czechia; Germany; Hungary; Italy; Japan; Lebanon; Malaysia; Netherlands; Philippines; Poland; Romania; Russia; South Africa; Spain; Ukraine; United Kingdom

References

Mahlangu J, Kuliczkowski K, Karim FA, Stasyshyn O, Kosinova MV, Lepatan LM, Skotnicki A, Boggio LN, Klamroth R, Oldenburg J, Hellmann A, Santagostino E, Baker RI, Fischer K, Gill JC, P'Ng S, Chowdary P, Escobar MA, Khayat CD, Rusen L, Bensen-Kennedy D, Blackman N, Limsakun T, Veldman A, St Ledger K, Pabinger I; AFFINITY Investigators. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood. 2016 Aug 4;128(5):630-7. doi: 10.1182/blood-2016-01-687434. Epub 2016 Jun 21.

Reference Type: DERIVED

PMID: 27330001 (View on PubMed)

Other Identifiers

2011-002393-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSL627_1001

Identifier Type: -

Identifier Source: org_study_id