Phase 3 Efficacy and Safety Study of BAX 855 in Severe Hemophilia A Patients Undergoing Surgical Procedures

NCT01913405 | Completed Phase 3 Results DMC

• 2 other identifiers: 2612042013-001359-11
• Study Type: interventional
• Target: 30
• Locations: 9 countries
• Sites: 22

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of BAX 855 in severe hemophilia A previously treated (PTP) males, 12 to 65 years of age who are undergoing elective surgical or other invasive procedures.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Global Hemostatic Efficacy Assessment Score (GHEA) - Composed of 3 Individual Ratings

  GHEA=Sum of 1-3 ratings: Excellent: 7-9 (no category \<2), Good: 5-7 (no category \<1), Fair: 3-4 (no category \<1) 1. Intraoperative and 2. Postoperative (postoperative day 1) hemostatic efficacy assessments: Excellent=3: Blood Loss (BL) ≤ than expected for procedure type in non-hemophilic population (NHP) (≤100%), Good=2: BL ≤50% more than expect. for procedure type in NHP (101-150%), Fair=1: BL \>50% more than expect. for procedure type in NHP (\>150%), None=0: Significant bleeding-requiring rescue therapy (RT) 3. Perioperative hemostatic efficacy assessment (day 14 or discharge, whatever is first): Excellent=3: BL and required blood transfusions (BT) less than or similar (≤100%) to that expected for procedure type in NHP, Good=2: BL ≤50% more (101-150%) and BT less than or similar to that expected for procedure type in NHP, Fair=1: BL \>50% more (\>150%) and BT greater than expected in NHP, None=0: Significant bleeding-requiring RT, BT substantially greater than expected in NHP

  Hemostatic efficacy assessments were performed intraoperatively, postoperatively on day 1 (approximately 24 hours after surgery) and perioperatively at day 14 or discharge (whichever was first).

Secondary Outcomes (24)

• Intraoperative Blood Loss

  From initiation of surgery until end of surgery.

• Postoperative Blood Loss

  From completion of surgery until 24 hours after surgery.

• Overall Perioperative Blood Loss

  From start of surgery until discharge or day 14, whichever occurred first.

• Transfusion Requirements

  From initiation of the surgery to 24 hours after completion of the surgery.

• Occurrence of Bleeding Episodes and Additional Need for Surgical Intervention

  Intra- and post-operative period, until the last intensified treatment after hospital discharge (minor surgery 1-3 days, major surgery average approximately 2 weeks)

Study Arms (1)

BAX855

EXPERIMENTAL

Pre-operative loading dose: Single loading dose, pre-surgery administered based on each study participant's individual PK results as well as target trough level for type and character of surgery, dental or invasive procedure being performed. In general, major surgery will target an 80-150% FVIII trough level, and minor surgery will target an initial 30-100% FVIII trough level. Intra-operative and post-operative dosing of BAX855 must be based on pre-dosage measurements of FVIII and the type and character of the surgery performed.

Biological: PEGylated Recombinant factor VIII (rFVIII)

Interventions

PEGylated Recombinant factor VIII (rFVIII) BIOLOGICAL

Lyophilized powder and solvent for solution for injection

Also known as: BAX 855, ADYNOVATE

BAX855

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:

• Participant requires an elective major or minor surgical, dental or other invasive procedure (e.g. biopsy, endoscopy).
• Participant and/or legal representative has/have provided signed informed consent.
• Participant has severe hemophilia A (Factor VIII (FVIII) level \<1%) as confirmed by the central lab at screening or a documented FVIII activity level \<1%.
• Participant was previously treated with FVIII concentrates with ≥150 documented exposure days (EDs).
• Participant is currently receiving prophylaxis or on-demand therapy with FVIII concentrate.
• Participant has a Karnofsky performance score of ≥60 at screening.
• Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥200 cells/mm\^3, as confirmed by central laboratory at screening.
• Participant is Hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis as assessed by the investigator.
• Participant is willing and able to comply with the requirements of the study protocol.

You may not qualify if:

• Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Unit (BU) using the Nijmegen modification of the Bethesda assay) at screening as determined by the central laboratory or at any timepoint prior to screening (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay).
• History of ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
• Participant has a platelet count \<100 x 10\^9/L, as confirmed by central laboratory at screening.
• Participant has severe renal impairment (serum creatinine \> 2.0 mg/dL), as confirmed by central laboratory at screening.
• Participant has severe chronic hepatic dysfunction (eg ≥5 X upper limit of normal alanine aminotransferase (ALT), as confirmed by the central laboratory at screening, or a documented International Normalized Ratio (INR) \> 1.5).
• Participant has a known hypersensitivity towards mouse or hamster proteins, polysorbate 80 or to PEG.
• Participant is currently using or has recently (\< 30 days) used pegylated drugs (other than BAX 855) prior to study participation or is scheduled to use such drugs during trial participation.
• Participant is currently participating in another clinical drug (other than BAX 855) or device study or use of another investigational product or device within 30 days prior to study entry.
• Participant has a diagnosis of an inherited or acquired hemostatic defect other than hemophilia A.
• Participant is currently receiving, or scheduled to receive during the course of the study, an immunomodulating drug (eg, systemic corticosteroid agent at a dose equivalent to hydrocortisone \>10 mg/day, or alpha interferon) other than anti-retroviral chemotherapy.
• Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (22)

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Bleeding and Clotting Disorders Institute

Peoria, Illinois, 61614, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Children's Mercy Hospitals & Clinics

Kansas City, Missouri, 64108, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

SHAT of Oncohaematology Diseases

Sofia, 1527, Bulgaria

Location

MHAT 'Sv. Marina', EAD

Varna, 9003, Bulgaria

Location

Vilnius University Hospital Santariskiu Clinics, Public Institution

Vilnius, 08661, Lithuania

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

FSHI "Kirov SR Institute of Hematology and Blood Transfusion FMBA"

Kirov, 610000, Russia

Location

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07010, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Málaga, 29010, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Universitaetsspital Zuerich

Zurich, 8091, Switzerland

Location

SI Institute of Blood Pathology and Transfusion Medicine of AMSU

Lviv, 79044, Ukraine

Location

Royal Free Hospital

London, Greater London, NW3 2QG, United Kingdom

Location

Great Ormond Street Hospital for Children

London, Greater London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, Greater Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Brand B, Gruppo R, Wynn TT, Griskevicius L, Lopez Fernandez MF, Chapman M, Dvorak T, Pavlova BG, Abbuehl BE. Efficacy and safety of pegylated full-length recombinant factor VIII with extended half-life for perioperative haemostasis in haemophilia A patients. Haemophilia. 2016 Jul;22(4):e251-8. doi: 10.1111/hae.12963. Epub 2016 Jun 21.

  PMID: 27328112 RESULT

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; BAX 855

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

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2013
• First Posted: August 1, 2013
• Study Start: December 20, 2013
• Primary Completion: September 23, 2016
• Study Completion: September 23, 2016
• Last Updated: May 24, 2021
• Results First Posted: May 14, 2018

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

CH (1); ES (4); LI (1); US (8); BU (2); NL (1); RU (1); GB (3); UA (1)