A Study of BAX 888 in Male Adults With Severe Hemophilia A

NCT03370172 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2015012015-005576-22
• Study Type: interventional
• Target: 4
• Locations: 6 countries
• Sites: 26

Brief Summary

The main aim of this study is to check if there are side effects from BAX 888 and to determine the dose of BAX 888 for treating severe hemophilia A in male adults. Participants will receive one infusion with BAX 888 at the hemophilia treatment center. During the study, participants will visit their study clinic multiple times.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Number of Participants With BAX 888-Related Adverse Events (AEs)

  An AE is defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. A Serious adverse event (SAE) is an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. AEs include both serious and non-serious adverse events including development of FVIII inhibitory antibodies, clinically significant changes in standard laboratory parameters, physical exam, and vital signs.

  From first dose up to end of the study (approximately 6 years)

Secondary Outcomes (8)

• Change From Baseline in Circulating Plasma FVIII Activity Level

  Baseline, up to Month 60

• Number of Participants With Clinically Significant Change From Baseline in Circulating Plasma FVIII Antigen Level

  Baseline, up to Month 60

• Annualized Bleed Rate (ABR)

  Up to approximately 6 years 4 months

• Percentage of Participants With a Reduction in Consumption of Exogenous FVIII

  Up to approximately 6 years 4 months

• Number of Participants Who Developed Inhibitory Antibodies to FVIII

  Up to approximately 6 years 4 months

Study Arms (2)

Cohort 1: BAX 888 2.0*10^12 cp/kg

EXPERIMENTAL

Cohort 1 participants received a single peripheral intravenous (IV) infusion of BAX 888 at a dose of 2.0\*10\^12 capsid particles per kilogram (cp/kg) on the day of dosing (Day 0).

Drug: BAX 888

Cohort 2: BAX 888 6.0*10^12 cp/kg

EXPERIMENTAL

Cohort 2 participants received a single peripheral IV infusion of BAX 888 at a dose of 6.0\*10\^12 cp/kg on the day of dosing (Day 0).

Drug: BAX 888

Interventions

BAX 888 DRUG

Participants will receive a single peripheral IV infusion of BAX 888 in Cohort 1 and 2 Day 0.

Also known as: Adeno-associated virus serotype 8 (AAV8) vector expressing B-domain deleted Factor VIII (BDD-FVIII), BAX888

Cohort 1: BAX 888 2.0*10^12 cp/kg; Cohort 2: BAX 888 6.0*10^12 cp/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, aged 18 to 75 years at the time of screening.
• Established severe hemophilia A (FVIII:C \<1%, measured following \>=5 days without FVIII treatment) and/or documented intron 1 inversion or intron 22 inversion mutation in the F8 gene, consistent with severe hemophilia A , and documented evidence of \>=3 hemorrhages over the previous 12 months requiring treatment with exogenous FVIII or use of FVIII prophylaxis because of history of frequent bleeding episodes.
• History of greater than (\>) 150 exposure days to exogenously administered FVIII concentrates or cryoprecipitate.
• Sexually active men must agree to use barrier contraception (combination of a condom and spermicide) or limit sexual intercourse to post-menopausal, surgically sterilized, or contraception-practicing partners for a minimum of 6 months after administration of BAX 888, or until BAX 888 genomes are no longer detected in the semen, whichever is sooner.
• Participant is willing and able to comply with the requirements of the protocol, including provision of semen samples, maintenance of a diary of bleeding episodes and FVIII protein use.
• Signed informed consent.

You may not qualify if:

• Bleeding disorder(s) other than hemophilia A.
• Personal laboratory evidence of having developed inhibitors to FVIII protein at any time (\>=0.6 Bethesda units \[BU\] on any single test).
• Documented prior allergic reaction to any FVIII product.
• Anti-Adeno-associated virus, serotype 8 (AAV8) neutralizing antibody titer \>=1:5. Participants whose laboratory assessments are less than or equal to (\<=) 1:10 may be re-tested within the same screening window and, if eligibility criterion is met on retest, may be enrolled after confirmation by the Sponsor Medical Monitor.
• Known hypersensitivity to prednisolone or prednisone, or to any of the excipients.
• Having a disease in which treatment with prednisolone or prednisone is not tolerated (including but not limited to osteoporosis with vertebral fractures, difficult to control hypertension, and difficult to control diabetes).
• Evidence of markers of potential underlying risk for autoimmune mediated hepatic disease:
• Anti-smooth muscle antibody assay results \>=40 (Inova QUANTA LiteTM Actin IgG enzyme-linked immunosorbent assay \[ELISA\]); values of 31 to 39 will be flagged as possibly abnormal and the Investigator and Medical Monitor will evaluate the participant for eligibility.
• Elevated anti-liver-kidney microsomal antibody type 1 (LKM1) titers.
• Total immunoglobulin G (IgG) \>1.5\*upper limit of normal (ULN).
• Antinuclear antibody (ANA) titer \>1:320; OR ANA titer \>1:80 if demonstrated concurrently with alanine aminotransferase (ALT) that is \>ULN.
• Active Hepatitis virus (Hepatitis C): As indicated by detectable hepatitis C virus (HCV) ribonucleic acid (RNA) by polymerase chain reaction (PCR).
• Hepatitis B: If surface antigen is positive.
• Seropositive for Human Immunodeficiency Virus (HIV).
• Receiving systemic antiviral and/or interferon therapy within 4 weeks prior to enrollment.

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Baxalta Innovations GmbH, now part of Shire: collaborator
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (26)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Orthopaedic Hospital DBA Orthopaedic Hemophilia Treatment Center

Los Angeles, California, 90007, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Colorado Hemophilia & Thrombosis Center

Aurora, Colorado, 80045, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Gulf States Hemophilia and Thrombophilia Center

Houston, Texas, 77030-4009, United States

Location

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

Location

Hôpital de la Timone

Marseille, Bouches-du-Rhône, 13385, France

Location

Hôpital Morvan

Brest, Finistere, 29609, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, 35000, France

Location

CHU Tours - Hôpital Trousseau

Tours, Indre Et Loire, 37044, France

Location

CHU de Nantes Site Hotel Dieu

Nantes, Loire Atlantique, 44093, France

Location

Hopital Jeanne de Flandre - CHU Lille

Lille, Nord, 59037, France

Location

Groupement Hospitalier Est- Hôpital Louis Pradel

Bron, Rhone, 69677, France

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, Val De Marne, 94275, France

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 01307, Germany

Location

Vivantes Klinikum im Friedrichshain

Berlin, 10249, Germany

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Hemophilia A

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

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: December 12, 2017
• Study Start: February 27, 2018
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); AU (1); DE (3); HU (1); ES (5); FR (8)