Gene Therapy for Hemophilia A

Recruiting at 17 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

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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 VIII gene into the human body by use of a viral vector to treat the disease. By replacing the defective gene with a healthy copy the human body may produce clotting factor on its own. Hemophilia A is a bleeding disorder in which the human body does not have enough clotting factor VIII, a protein that controls bleeding. Researcher want to find the optimal dose of BAY 2599023 (DTX201) so that the body may produce enough clotting factor on its own.

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 BAY2599023 (DTX201) gene therapy for Hemophilia A safe for humans?

The safety of BAY2599023 (DTX201) gene therapy for Hemophilia A is still being evaluated, but early clinical trials have not reported significant adverse side effects. The therapy uses adeno-associated viral (AAV) vectors, which have been used in other gene therapies with no major safety concerns reported so far. ^{1 2 3 4 5}

How is the treatment BAY2599023 (DTX201) unique for hemophilia A?

BAY2599023 (DTX201) is a gene therapy that uses a specific type of viral vector to deliver a modified gene to help the body produce its own Factor VIII, which is missing in people with hemophilia A. This approach aims for a one-time treatment that could provide long-term protection from bleeding, unlike regular infusions of Factor VIII that are currently needed. ^{1 3 6 7 8}

What data supports the effectiveness of the treatment BAY2599023 (DTX201) for Hemophilia A?

Research shows that gene therapy using adeno-associated virus (AAV) vectors, like BAY2599023, has been effective in increasing Factor VIII levels in patients with Hemophilia A, reducing bleeding episodes and the need for regular treatments. This approach has shown promising results in clinical trials, suggesting it could significantly improve the quality of life for patients. ^{1 6 9 10 11}

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%.

I have used Factor VIII concentrates for more than 150 days.

Exclusion Criteria

Detectable antibodies reactive with AAVhu37capsid

I have a bleeding disorder that is not hemophilia A.

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

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]

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]

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]

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]

Citations

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Gene therapy for hemophilia. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Gene therapy of hemophilia. [2012]

5. England pubmed.ncbi.nlm.nih.gov

Long-term correction of hemophilia A mice following lentiviral mediated delivery of an optimized canine factor VIII gene. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Development of a Clinical Candidate AAV3 Vector for Gene Therapy of Hemophilia B. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Gene therapy for hemophilia. [2012]

8. United States pubmed.ncbi.nlm.nih.gov

Coagulation factor IX gene transfer to non-human primates using engineered AAV3 capsid and hepatic optimized expression cassette. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. [2022]

10. United States 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. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes. [2020]