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

NCT01486927 | Completed Phase 2 Results

• 2 other identifiers: CSL627_10012011-002393-23
• Study Type: interventional
• Target: 175
• Locations: 19 countries
• Sites: 54

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

Outcome Measures

Primary Outcomes (4)

• Treatment Success

  The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.

  Up to 24 months

• Inhibitor Formation to FVIII

  Number of subjects who develop inhibitors to FVIII

  Up to 24 months

• Annualized Spontaneous Bleeding Rate

  The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25\*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).

  Up to 24 months

• Treatment Success During the Peri-operative Surgical Sub-study

  Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.

  From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

Secondary Outcomes (10)

• AUC0-∞ (Part 1)

  Before infusion and at up to 10 time points within 72 hours of infusion

• Cmax (Part 1)

  Before infusion and at up to 10 time points within 72 hours of infusion

• Tmax (Part 1)

  Before infusion and at up to 10 time points within 72 hours of infusion

• Half-life (t1/2) (Part 1)

  Before infusion and at up to 10 time points within 72 hours of infusion.

• Mean Residence Time (MRT) (Part 1)

  Before infusion and at up to 10 time points within 72 hours of infusion

Other Outcomes (8)

• Incremental Recovery (Part 3)

  At 30 minutes after infusion

• Volume of Distribution at Steady-state (Vss) (Part 3)

  Before infusion and at up to 12 time points within 96 hours of infusion.

• Clearance (Cl) (Part 3)

  Before infusion and at up to 12 time points within 96 hours of infusion.

Study Arms (1)

Recombinant Factor VIII (rFVIII)

EXPERIMENTAL

Biological: rVIII-SingleChain; Biological: Octocog alfa

Interventions

rVIII-SingleChain 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.

Also known as: Recombinant Factor VIII (rFVIII), CSL627

Recombinant Factor VIII (rFVIII)

Octocog alfa 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.

Also known as: Human coagulation factor VIII (rDNA)

Recombinant Factor VIII (rFVIII)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (56)

Study Site

Sacramento, California, 95817, United States

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San Diego, California, 92103, United States

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Aurora, Colorado, 80045, United States

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Hartford, Connecticut, 06106, United States

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Miami, Florida, 33136, United States

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Chicago, Illinois, 60612-3833, United States

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New Orleans, Louisiana, 70112, United States

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Houston, Texas, 77030, United States

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Milwaukee, Wisconsin, 53226, United States

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Nedlands, WA 6009, Australia

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Perth, WA 6000, Australia

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Graz, 8036, Austria

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Vienna, 1090, Austria

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New Brunswick, E2L 4L2, Canada

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Hradec Králové, 500 05, Czechia

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Berlin, 10249, Germany

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Berlin, 13353, Germany

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Bonn, 53127, Germany

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Giessen, 35392, Germany

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Hamburg, 20095, Germany

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Hanover, 30159, Germany

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Heidelberg, 69123, Germany

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Debrecen, H-4032, Hungary

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Florence, 50134, Italy

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Milan, 20122, Italy

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Padua, 35123, Italy

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Padua, 35128, Italy

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Torino, 10126, Italy

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Kashihara, Nara, Japan

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Kitakyushu, Fukuoka, Japan

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Nagoya, 466-85660, Japan

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Nishinomiya, Hyogo, Japan

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Okayama, 710-8602, Japan

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Saitama, Japan

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Suginami-ku, Tokyo, Japan

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Tokyo, 160-0023, Japan

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Beirut, Lebanon

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Kuala Lumpur, 50400, Malaysia

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Utrecht, 3584 CX, Netherlands

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Cebu City, 6000, Philippines

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Davao City, 8000, Philippines

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Wroclaw, Silesian Voivodeship, 50-367, Poland

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Gdansk, 80-952, Poland

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Krakow, 31-501, Poland

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Bucharest, 011026, Romania

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Barnaul, 656038, Russia

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Kemerovo, 650066, Russia

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Cape Town, 7295, South Africa

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Johannesburg, 2193, South Africa

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A Coruña, Spain

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Barcelona, Spain

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Valencia, 46026, Spain

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Dnipropetrovsk, 49102, Ukraine

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Donetsk, 830045, Ukraine

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Lviv, 79044, Ukraine

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London, NW3 2QG, United Kingdom

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Related Publications (1)

• 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.

  PMID: 27330001 DERIVED

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; F8 protein, human; DNA, Ribosomal

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

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors; DNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2011
• First Posted: December 7, 2011
• Study Start: February 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 9, 2016
• Results First Posted: August 9, 2016

Record last verified: 2016-06

Locations

ES (3); MY (1); JP (8); RU (2); NL (1); CA (1); HU (1); CZ (1); LE (1); DE (7); UA (3); RO (1); IT (5); GB (1); PL (3); AU (2); PH (2); ZA (2); US (9)