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Hemophilia APhase 1/2NCT03370172

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

A Phase 1/2 study testing BAX 888 in people with Hemophilia A, run by Baxalta now part of Shire at 26 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years, men only
Conditions the study is for
Hemophilia A
What is being tested?
BAX 888
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
26 sitesin 6 countries
Study dates
27 Feb 2018to 9 Jul 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 39Show fewer
  • 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.
  • Clinically significant infections (e.g. systemic fungal infections) requiring systemic treatment.
  • Known immune disorder (including myeloma and lymphoma).
  • Concurrent chemotherapy or biological therapy for treatment of neoplastic disease or other disorders.
  • An absolute neutrophil count <1000 cells per cubic millimeter (cells/mm^3).
  • Markers of hepatic inflammation or cirrhosis as evidenced by 1 or more of the following:
  • Platelet count of <150,000/microliter (mcL).
  • Serum albumin level is below the central laboratory's lower limit of normal and FibroSURE is >=0.48 (i.e., Metavir staging of F2 or greater). Of note, in participants with a known history of Gilbert's syndrome, a Fibrotest cannot be used for fibrosis testing.
  • Total bilirubin >1.5*ULN and direct bilirubin >=0.5 milligram per deciliter (mg/dL).
  • ALT or aspartate aminotransferase (AST) >1.0*ULN.
  • Alkaline phosphatase (AP) >2.0*ULN.
  • History of liver biopsy indicating moderate or severe fibrosis (Metavir staging of F2 or greater).
  • History of ascites, varices, variceal hemorrhage, or hepatic encephalopathy.
  • Any findings on screening ultrasound that would preclude the safe use of AAV gene therapy.
  • Prothrombin time (PT) international normalized ratio (INR) >=1.4.
  • Serum creatinine >1.5 mg/dL.
  • Urine protein >30 mg/dL or >0.5 gram per day (g/day).
  • Body mass index >38.
  • Major surgery or an orthopedic surgical procedure planned within 6 months after enrollment.
  • Acute or chronic disease that, in the opinion of the investigator, would adversely affect participant safety or compliance or interpretation of study results.
  • Received an AAV vector previously or any other gene transfer agent in the previous 12 months prior to Study Day 0.
  • Received an investigational intervention or participated in another clinical trial within 4 weeks prior to enrollment or within 5 half-lives of the investigational drug administration, whichever is longer.
  • Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease).
  • Recent history of psychiatric illness or cognitive dysfunction (including drug or alcohol abuse) that in the opinion of the investigator, is likely to impair participants ability to comply with protocol mandated procedures.
  • Participant is a family member or employee of the investigator.

Trial locations and contacts

26 sites in 6 countries.

26 sites in 6 countries

United States8 sites

  • University of Colorado Hemophilia & Thrombosis Center

    Aurora, Colorado, 80045

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Gulf States Hemophilia and Thrombophilia Center

    Houston, Texas, 77030-4009

  • Orthopaedic Hospital DBA Orthopaedic Hemophilia Treatment Center

    Los Angeles, California, 90007

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • UC Davis Medical Center

    Sacramento, California, 95817

Other trials in United States

France8 sites

  • Hôpital Morvan

    Brest, Finistere, 29609

  • Groupement Hospitalier Est- Hôpital Louis Pradel

    Bron, Rhone, 69677

  • Hôpital Bicêtre

    Le Kremlin-Bicêtre, Val De Marne, 94275

  • Hopital Jeanne de Flandre - CHU Lille

    Lille, Nord, 59037

  • Hôpital de la Timone

    Marseille, Bouches-du-Rhône, 13385

  • CHU de Nantes Site Hotel Dieu

    Nantes, Loire Atlantique, 44093

  • CHU Rennes - Hopital Pontchaillou

    Rennes, Ille Et Vilaine, 35000

  • CHU Tours - Hôpital Trousseau

    Tours, Indre Et Loire, 37044

Other trials in France

Spain5 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Regional Universitario de Malaga

    Málaga, 29010

  • Hospital Clinico Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

Other trials in Spain

Germany3 sites

  • Vivantes Klinikum im Friedrichshain

    Berlin, 10249

  • Universitaetsklinikum Carl Gustav Carus TU Dresden

    Dresden, Saxony, 01307

  • Klinikum der Johann Wolfgang Goethe-Universitaet

    Frankfurt am Main, Hesse, 60590

Other trials in Germany

Austria1 site

  • AKH - Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

Hungary1 site

  • Semmelweis Egyetem

    Budapest, 1083

Other trials in Hungary

About this study

Official title: A Global, Open-Label, Multicenter, Phase 1/2 Study of the Safety and Dose Escalation of BAX 888, an Adeno-Associated Virus Serotype 8 (AAV8) Vector Expressing B-Domain Deleted Factor VIII (BDD-FVIII) in Severe Hemophilia A Subjects Administered a Single Intravenous Infusion

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.

Read the detailed description

This study consists of 3 cohorts. Participants will be assigned to 1 of 3 dose cohorts with a minimum of 24 hours between dosing of each participant. Initially, 2 participants will be dosed in a cohort, with up to a total of 5 participants if the cohort is expanded based on safety and activity levels data.

Dose escalation: After dosing first 2 participants in cohort 1 the decision will be made on the following: If week 4 FVIII activity levels of both participants are less than (<) 2%, then dose escalation to cohort 2 will be triggered with no further dosing in cohort 1. If FVIII activity levels >=2% are observed in at least 1 participant among the 2 participants the decision to escalate dose or expand the cohort with dosing of additional participants will be based on all available data through Week 14.

Dose expansion: After dose escalation and administration of BAX 888 to the first 2 participants in 3 cohorts: If sustained Week 14 FVIII activity levels are >=30% are not achieved in both participants (first 2 participants in cohorts 1 and 2) then escalation to immediate next cohort will be triggered after Data Monitoring Committee (DMC) review of all available safety and FVIII activity levels data. For cohort 3 dosing of additional participants will be paused until further review of available data. If sustained Week 14 FVIII levels are >=30% in at least 1 of the 2 participants (first 2 participant in cohort 1, 2, 3) then expansion of cohorts 1, 2 (with up to 5 participants), 3 (with up to 3 additional participants) will be initiated with dosing or study could be completed with no further dosing.

23 APRIL 2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

Conditions
Hemophilia A
Being tested
BAX 888
Medical subject headings
Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAX 888Drug

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

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

Study groups in NCT03370172
Study groupRoleWhat they receive
Cohort 1: BAX 888 2.0*10^12 cp/kgExperimentalCohort 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).
Receives: Drug: BAX 888
Cohort 2: BAX 888 6.0*10^12 cp/kgExperimentalCohort 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).
Receives: Drug: BAX 888

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)

  1. Change From Baseline in Circulating Plasma FVIII Activity Level

    Change from baseline in circulating plasma FVIII activity level, based on one-stage clotting assay was assessed.

    Measured: Baseline, up to Month 60

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

    Change from baseline in circulating plasma FVIII antigen (protein) levels were to be assessed and number of participants with clinically significant change as determined by the principal investigator (PI) were reported.

    Measured: Baseline, up to Month 60

  3. Annualized Bleed Rate (ABR)

    ABR in comparison to before gene transfer will be assessed. A bleed is defined as subjective or objective evidence of bleeding which may or may not require treatment with FVIII. ABR was calculated as (number of bleeding episodes/observed treatment period in days)*365.25.

    Measured: Up to approximately 6 years 4 months

  4. Percentage of Participants With a Reduction in Consumption of Exogenous FVIII

    The reduction in consumption of exogenous FVIII was assessed by comparing the amount of exogenous FVIII taken at earliest time point available (prior to BAX 888 infusion) with the amount taken at the last post-infusion timepoint available, during the study. Percentage of participants with reduction in consumption of exogenous FVIII are reported.

    Measured: Up to approximately 6 years 4 months

  5. Number of Participants Who Developed Inhibitory Antibodies to FVIII

    Participants were assessed to check if they developed inhibitory antibodies to FVIII.

    Measured: Up to approximately 6 years 4 months

  6. Number of Participants Who Developed Total Binding Antibodies to FVIII

    Participants were assessed to check if they developed total binding antibodies to FVIII (Immunoglobulin G [IgG], Immunoglobulin M [IgM]).

    Measured: Up to approximately 6 years 4 months

  7. Number of Participants With Humoral and Cell-Mediated Immune Response to AAV8 and FVIII Proteins

    The humoral (antibody-mediated) and cell-mediated immune response to adeno-associated virus (AAV8) (the vector) and FVIII proteins, was assessed. Humoral Immune Response: It is indicated by presence of specific antibodies. The anti-AAV8 binding antibodies, IgG or IgM were measured by the enzyme-linked immunosorbent assay (ELISA) method. Neutralizing antibodies were measured by a cell-based luminescent assay. Cell-mediated Immune response: The AAV8 and FVIII specific cell mediated immunity was assessed using validated interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays. This assay tests the human T-cell recall response to the AAV8 and FVIII proteins. These proteins were called antigens for these tests (AAV8 peptide pools 1, 2, 3 and two pooled test antigens (1 and 2) for FVIII). Number of participants who had humoral and/or cell mediated immune response to AAV8 and FVIII proteins, are reported by humoral and cell mediated immune response categories.

    Measured: Up to approximately 6 years 4 months

  8. Surveillance of AAV8 Genome Shedding

    Surveillance of AAV8 genome shedding in blood, saliva, semen, stool and urine until two consecutive negative results were assessed.

    Measured: Blood: Day 1, weekly at Clinic Visits between Weeks 1-15, and at Months 4 and 5; Saliva, Semen, and Stool: Day 1 and Week 1; Urine: Day 1 and Weeks 1,2,3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2017
  2. Study start27 Feb 2018
  3. Primary completion9 Jul 2024
  4. Study completion9 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03370172
Sponsor's protocol ID
201501
Other IDs
2015-005576-22, 2015
Status last verified
Aug 2025
First submitted
22 Nov 2017
Last updated
11 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Takeda does not provide access to Individual Participant Data when a study is in a very limited (small) study population due to participant privacy concerns such as potential reidentification of study participants.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BAX 888 in people with Hemophilia A, run by Baxalta now part of Shire at 26 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, France, Spain, Germany, Austria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With BAX 888-Related Adverse Events (AEs) (time frame: From first dose up to end of the study (approximately 6 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03370172.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.

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