Gene Therapy for Hemophilia A

Not currently recruiting at 19 trial locations

Overseen By For trial location information (Phone Menu Options '3' or '4')

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Bayer

Must not be taking: Antivirals, FVIII inhibitors

Disqualifiers: Obesity, Hepatitis, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, based on dose-finding

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gene therapy called BAY 2599023 (DTX201) for individuals with hemophilia A, a condition where the body lacks enough protein to stop bleeding. The goal is to determine if this treatment can safely and effectively enable the body to produce its own clotting factor by delivering a healthy gene. Researchers aim to identify the optimal dose for this therapy. Men with severe hemophilia A, who have previously used clotting products and experience frequent bleeding episodes, might be suitable for this study. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial requires participants on prophylactic treatment to be willing to stop at specified times during the study. If you are on-demand, you should have had more than 4 bleeding events in the last year.

Is there any evidence suggesting that BAY2599023 (DTX201) is likely to be safe for humans?

Research has shown that earlier studies of BAY 2599023 (DTX201) examined its safety for individuals with severe hemophilia A. This gene therapy helps the body produce its own clotting factor, essential for stopping bleeding.

In these studies, patients generally tolerated BAY 2599023 well, with no serious side effects directly linked to the therapy. Some patients experienced mild side effects, such as temporary increases in liver enzymes, which were mostly manageable and did not cause long-term issues.

As this study remains in the early stages, researchers continue to collect safety data. Initial results are promising, indicating that the treatment is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hemophilia A?

Unlike the standard treatments for hemophilia A, which typically involve regular infusions of clotting factor VIII, BAY2599023 (DTX201) offers a novel approach through gene therapy. This treatment is unique because it aims to provide a long-term solution by introducing a functional gene that enables the patient's body to produce its own clotting factor. Researchers are excited about BAY2599023 because it has the potential to significantly reduce or even eliminate the need for frequent infusions, offering a more sustainable and convenient option for individuals with severe hemophilia A.

What evidence suggests that this treatment might be an effective treatment for Hemophilia A?

Research has shown that BAY 2599023 (DTX201), a gene therapy for hemophilia A, appears promising in early studies. This treatment provides the body with a healthy version of the factor VIII gene, enabling it to produce the necessary clotting factor independently. In past studies, BAY 2599023 maintained factor VIII levels for up to 23 months, significantly reducing bleeding episodes. These results suggest that the treatment could effectively manage hemophilia A by addressing its root cause: the lack of factor VIII. Although more research is needed, these findings offer hope for those with severe hemophilia A. Participants in this trial will receive BAY 2599023 to further evaluate its effectiveness and safety. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adult males with severe Hemophilia A, evidenced by very low clotting factor VIII levels and a history of frequent bleeding. Participants must have used clotting factor concentrates extensively and be willing to pause any prophylactic treatments during the study. They should not be obese, have no inhibitors against factor VIII or significant liver disease, no active hepatitis B or C, nor HIV with low CD4 counts.

Inclusion Criteria

I am a man aged 18 or older.

My hemophilia A diagnosis shows FVIII activity levels below 1%.

Agree to use reliable barrier contraception

Exclusion Criteria

I have a bleeding disorder that is not hemophilia A.

Detectable antibodies reactive with AAVhu37capsid

Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BAY 2599023 (DTX201) to deliver a healthy version of the Factor VIII gene

Variable, based on dose-finding

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• BAY2599023 (DTX201)

Trial Overview Researchers are testing BAY 2599023 (DTX201), which uses a modified virus to deliver a healthy gene for clotting factor VIII into liver cells. The goal is to enable patients' bodies to produce enough of this protein on their own, potentially improving blood clotting in those with Hemophilia A.

How Is the Trial Designed?

Group I: BAY2599023 / (DTX201) Experimental Treatment 1 Intervention

Adult patients with severe hemophilia A, who have been previously treated with FVIII products

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Ultragenix pharmaceutical

Collaborator

Trials

1

Recruited

10+

Published Research Related to This Trial

Recent advancements in gene therapy for hemophilia A and B, particularly using adeno-associated virus (AAV) vectors, have shown promising results in increasing factor VIII and IX levels, leading to a significant reduction in bleeding episodes and the need for prophylactic treatments in most patients.

While the clinical benefits of gene therapy are evident, ongoing trials also highlight potential side effects and limitations that need to be addressed before these therapies can be widely implemented for hemophilia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for hemophilia: a review on clinical benefit, limitations, and remaining issues. Leebeek, FWG., Miesbach, W.[2021]

The novel adenovirus vector Ad-E4-122aT showed significantly higher transduction efficiencies in neonatal hemophilia B mice compared to conventional vectors, indicating its potential for effective gene therapy.

A single injection of Ad-E4-122aT expressing human factor IX maintained therapeutic levels of the protein for about 100 days, and sequential doses resulted in levels exceeding normal, effectively rescuing bleeding symptoms in the mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes. Iizuka, S., Sakurai, F., Tachibana, M., et al.[2020]

Gene therapy for Hemophilia A aims to provide a single treatment that enables the body to produce its own Factor VIII (FVIII), potentially leading to significant improvements in bleeding protection and quality of life for patients.

The BAY 2599023 gene therapy product, which uses a specific AAV vector, shows promise due to its low prevalence of anti-AAV-hu37 antibodies, which may enhance patient eligibility and safety compared to other AAV-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy. Pipe, SW., Arruda, VR., Lange, C., et al.[2023]

AMT-060, a gene therapy for severe hemophilia B, demonstrated sustained factor IX (FIX) activity of 3%-13% and significantly reduced spontaneous bleeding without causing T cell-mediated liver toxicity in patients.

The modified version, AMT-061, showed a 6.5-fold increase in FIX activity compared to AMT-060 in non-human primates, while maintaining a similar safety profile, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced Factor IX Activity following Administration of AAV5-R338L "Padua" Factor IX versus AAV5 WT Human Factor IX in NHPs. Spronck, EA., Liu, YP., Lubelski, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03588299

NCT03588299 | Study to Test the Safety and How Well ... In this study researchers want to gather more information about safety and effectiveness of BAY 2599023 (DTX201), a drug therapy that delivers the human factor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10186383/

Characteristics of BAY 2599023 in the Current Treatment ... Efficacy and safety of valoctocogene roxaparvovec adeno-associated virus gene transfer for severe hemophilia A: Results from the phase 3 GENEr8-1 trial.

3. clinicaltrials.bayer.com clinicaltrials.bayer.com/study/19429

Hemophilia A | Study 19429 | Bayer - Clinical Trials Explorer Study to test the safety and how well patients with severe hemophilia A respond to treatment with BAY 2599023 (DTX 201), a drug therapy that delivers a healthy ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03588299?term=NCT03588299&rank=1

NCT03588299 | Study to Test the Safety and How Well ... In this study researchers want to gather more information about safety and effectiveness of BAY 2599023 (DTX201), a drug therapy that delivers the human factor ...

5. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/3971/481162/First-in-Human-Dose-Finding-Study-of-AAVhu37

BAY 2599023 Has Stable and Sustained Expression of FVIII ... BAY 2599023 delivered sustained FVIII expression levels for up to >23 months, with evidence of bleed protection.