BAX 888 for Hemophilia A

No longer recruiting at 41 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Baxalta now part of Shire

Must not be taking: Antivirals, Interferons, Chemotherapy, others

Disqualifiers: Bleeding disorders, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called BAX 888 for severe hemophilia A, a condition where blood doesn't clot properly, leading to frequent bleeding episodes. Researchers seek to identify any side effects and determine the right dose. Participants will receive a single infusion and attend several follow-up clinic visits. Men with a history of severe hemophilia A, who have experienced frequent bleeding in the past year and have used specific treatments, may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop your current medications. However, if you are on systemic antiviral or interferon therapy, you must stop it at least 4 weeks before enrolling.

Is there any evidence suggesting that BAX 888 is likely to be safe for humans?

Earlier research tested BAX 888 for safety in people with severe hemophilia A. BAX 888 is a gene therapy that helps the body produce a protein needed to stop bleeding in these individuals. The research shows that BAX 888 has been modified to reduce the chance of immune system reactions, meaning the body might not see it as a threat, which is beneficial for safety.

Currently, BAX 888 has undergone early studies focused on safety. These studies are the first steps in understanding how well people can tolerate it. As it remains in the early stages, researchers continue to learn about its safety. So far, it appears well-tolerated, but a clearer understanding will emerge as more people participate in ongoing studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about BAX 888 because it offers a unique approach to treating Hemophilia A. Unlike current treatments that often require regular infusions of clotting factor VIII, BAX 888 is a gene therapy designed to provide a long-term solution by potentially enabling the body to produce its own factor VIII. This treatment is administered as a single peripheral IV infusion, which could reduce the frequency of treatment compared to the standard of care. With two different dosing groups being explored, BAX 888 has the potential to significantly improve the quality of life for individuals with Hemophilia A by reducing bleeding episodes and minimizing the burden of ongoing treatment.

What evidence suggests that BAX 888 might be an effective treatment for hemophilia A?

Research shows that BAX 888 is a promising gene therapy being tested for hemophilia A, a condition where blood doesn't clot properly. The trial includes two separate treatment arms: one where participants receive a single peripheral IV infusion of BAX 888 at a dose of 2.0*10^12 cp/kg, and another where participants receive a dose of 6.0*10^12 cp/kg. This treatment uses a harmless virus to deliver a copy of the factor VIII gene, which helps blood to clot. Studies indicate that this method can reduce bleeding by increasing factor VIII levels in the blood. The therapy has been adjusted to lower the risk of causing an immune reaction, a common issue with gene therapies. Early studies suggest BAX 888 could be effective, but more research is needed to confirm its long-term benefits and safety. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Shire

Are You a Good Fit for This Trial?

This trial is for male adults aged 18-75 with severe hemophilia A, who have had more than 150 exposure days to FVIII treatments and at least three bleeding episodes in the past year. Participants must be willing to use barrier contraception and comply with study requirements like providing semen samples and keeping a diary of bleeding episodes.

Inclusion Criteria

Signed informed consent

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

I am a man between 18 and 75 years old.

Exclusion Criteria

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

My body does not strongly fight off the AAV8 virus used in treatment.

I have a known immune disorder such as myeloma or lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of BAX 888 at varying doses depending on cohort assignment

1 day

1 visit (in-person)

Dose Escalation and Expansion

Participants are monitored for FVIII activity levels to determine dose escalation or cohort expansion

14 weeks

Follow-up

Participants are monitored for safety, effectiveness, and immune response after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• BAX 888

Trial Overview The trial is testing BAX 888's safety and determining its proper dose for treating severe hemophilia A. Participants will receive one infusion of BAX 888 at a treatment center and make multiple visits to their study clinic for monitoring.

How Is the Trial Designed?

Group I: Cohort 2: BAX 888 6.0*10^12 cp/kg Experimental Treatment 1 Intervention

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).

Group II: Cohort 1: BAX 888 2.0*10^12 cp/kg Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

Baxalta now part of Shire

Lead Sponsor

Trials

111

Recruited

9,100+

Flemming Ornskov

Baxalta now part of Shire

Chief Executive Officer since 2013

MD, MPH

Ludwig N. Hantson

Baxalta now part of Shire

Chief Medical Officer since 2015

PhD

Baxalta Innovations GmbH, now part of Shire

Industry Sponsor

Trials

19

Recruited

8,000+

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11780198/

A phase 1/2 safety and efficacy study of TAK‐754 gene ... TAK 754 (BAX 888) is an investigational AAV8‐based gene therapy containing a FVIII transgene. Reduction in CpG motifs was performed to reduce immunogenicity.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03370172

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

3. clinicaltrials.takeda.com clinicaltrials.takeda.com/study-detail/5f6b5fc54db2bf003ab45cf2

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

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/hae.15121

A phase 1/2 safety and efficacy study of TAK‐754 gene ... TAK 754 (BAX 888) is an investigational AAV8-based gene therapy containing a FVIII transgene. Reduction in CpG motifs was performed to reduce ...

5. researchgate.net researchgate.net/publication/368748346_Two-Year_Outcomes_of_Valoctocogene_Roxaparvovec_Therapy_for_Hemophilia_A

Two-Year Outcomes of Valoctocogene Roxaparvovec ... The study data show the durability of factor VIII activity and bleeding reduction and the safety profile of valoctocogene roxaparvovec at least 2 years after ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39716875/?utm_source=WordPress&utm_medium=rss&utm_campaign=None&utm_content=1LceN0X8SIzfd8ViLpWwyW79lmrRIpBzZ_1bzYzuEWKUSPlc3W&fc=None&ff=20241225235959&v=2.18.0.post9+e462414

A phase 1/2 safety and efficacy study of TAK-754 gene ... TAK 754 (BAX 888) is an investigational AAV8-based gene therapy containing a FVIII transgene. Reduction in CpG motifs was performed to reduce immunogenicity.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2329050125000191

Preclinical development of TAK-754, a high-performance ... Here, we describe preclinical development of the recombinant single-stranded (ss) gene therapy vector TAK-754 (formerly BAX 888 and SHP654; Baxalta US, ...