Study of a pd vWF/FVIII, Biostate®, in Subjects With Haemophilia A

NCT00879541 | Completed Phase 2 DMC

• 2 other identifiers: CSLCT-BIO-07-471472
• Study Type: interventional
• Target: 81
• Locations: 4 countries
• Sites: 14

Brief Summary

The aim of this study are to

• assess the efficacy of Biostate® \[Study Product (SP)\] in subjects with Haemophilia A
• compare the pharmacokinetics of Biostate® \[SP\] with the previously marketed product Biostate® (here referred to as Biostate® \[Reference Product (RP)\]). This study is divided into 3 parts: Part 1: Cross-over pharmacokinetic (PK) component. PK subjects will be randomised to determine the order in which they receive the two study products. This part of the study is double-blinded. Part 2: Efficacy component. All subjects will receive Biostate® \[SP\] as required to manage their haemophilia condition for an estimated period of 6 months (or minimum of 50 exposure days) to assess efficacy and safety of the product. This part of the study is open-label. Part 3: Repeat pharmacokinetic assessment. Subjects who participated in Part 1 (PK component) will undergo a repeat PK assessment on Day 180 following administration of Biostate® \[SP\].

Conditions

Hemophilia A

Keywords

Hemophilia A

Outcome Measures

Primary Outcomes (5)

• Haemostatic efficacy

  Monthly, until final study visit

• Number of treatments/units required to resolve any bleeding event

  From Day 1 until final study visit

• FVIII concentrate usage (number of infusions, IU/kg per event, per month, and per year)

  From Day 1 until final study visit

• Assessment of blood loss during any surgical procedure

  From Day 1 until final study visit

• Pharmacokinetics of FVIII activity

  Up to 48 hours following infusions (Part 1 and Part 3 only)

Secondary Outcomes (2)

• The nature, frequency and incidence of adverse events

  From Day 1 until final study visit

• Development of FVIII inhibitors

  From Day 1 until final study visit

Study Arms (3)

PK Biostate® [SP]

OTHER

Part 1: PK subjects are randomized to receive Biostate® \[SP\] either on Day 1 or Day 8. Part 3: All PK subjects receive Biostate® \[SP\] on Day 180.

Biological: Biostate® [SP]

PK Biostate® [RP]

OTHER

Part 1: PK subjects are randomized to receive Biostate® \[RP\] either on Day 1 or Day 8.

Biological: Biostate® [RP]

Efficacy

EXPERIMENTAL

Part 2: This arm includes all subjects during the efficacy component of the study.

Biological: Biostate® [SP]

Interventions

Biostate® [SP] BIOLOGICAL

Single bolus intravenous dose of 50 IU/kg

Also known as: Human Coagulation Factor VIII / von Willebrand Factor

PK Biostate® [SP]

Biostate® [RP] BIOLOGICAL

Single bolus intravenous dose of 50 IU/kg.

Also known as: Biostate®, Human Coagulation Factor VIII / von Willebrand Factor

PK Biostate® [RP]

Eligibility Criteria

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

You may qualify if:

• Diagnosed with Haemophilia A with ≤ 1% Factor VIII (FVIII) levels in the absence of factor replacement
• Evidence of vaccination against hepatitis A and B (or presence of antibodies against hepatitis A and B due to either a previous infection or prior immunisation) within 10 years prior to Day 1 documented in the medical notes
• At least 150 days of prior exposure to a FVIII replacement product
• Written informed consent given

You may not qualify if:

• Active bleeding
• Body weight \> 100 kg
• Receipt of an infusion of any FVIII product, cryoprecipitate, whole blood, plasma, or desmopressin acetate (DDAVP) in the 4 days prior to Day 1
• Known history of FVIII inhibitors, or FVIII inhibitor level \> 0.6 Bethesda Units (BU) at screening
• Receipt of aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within 7 days of administration of study product.
• CD4 lymphocytes \< 200/µL. Subjects wo are HIV-1 positive may be considered for the study if viral load ≤ 200 particles/µL at screening and all other eligibility criteria are met.
• Impaired liver function ie. bilirubin \>1.5 x upper limit of normal (ULN) and/or AST/ALT \> 2.5 x ULN at screening.
• Acute or chronic medical condition, other than haemophilia A, which may, in the opinion of the Investigator, affect the conduct of the study
• von Willebrand Disease (VWD) with Von Willebrand Factor:Ristocetin Cofactor (vWF:RCo) level \< 50 IU/dL at screening
• Evidence or a history (within the previous 12 months) of abuse of any drug substance, licit or illicit
• Known or suspected hypersensitivity or previous evidence of severe side effects to Biostate®, FVIII concentrates or human albumin
• Participation in a clinical study or use of an investigational compound (e.g. a new chemical entity not approved for clinical use) in the 3 months preceding the first day of study drug administration, or plans to enter such a study during the study period
• Not willing and/or not able to comply with study requirements

Sponsors & Collaborators

• CSL Behring: lead
• Parexel: collaborator

Study Sites (14)

Study Site

Plovdiv, Bulgaria

Location

Study Site

Sofia, Bulgaria

Location

Study Site

Varna, Bulgaria

Location

Study Site

Skopje, North Macedonia

Location

Study Site

Bialystok, Poland

Location

Study Site

Gdansk, Poland

Location

Study Site

Krakow, Poland

Location

Study Site

Lublin, Poland

Location

Study Site

Poznan, Poland

Location

Study Site

Warsaw, Poland

Location

Study Site

Wroclaw, Poland

Location

Study Site

Barnaul, Russia

Location

Study Site

Kirov, Russia

Location

Study Site

Moscow, Russia

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; von Willebrand Factor

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 9, 2009
• First Posted: April 10, 2009
• Study Start: February 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: February 11, 2011

Record last verified: 2011-02

Locations

PL (7); NO (1); BU (3); RU (3)