Gene Therapy for Hemophilia A

Overseen By Clinical Trial Manager, PhD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: ASC Therapeutics

Must be taking: FVIII replacement

Must not be taking: Anticoagulants, Antivirals

Disqualifiers: Liver fibrosis, Renal disease, Infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new gene therapy for hemophilia A patients. It uses a harmless virus to help liver cells produce a missing protein needed for blood clotting. This could reduce the need for frequent injections. The therapy aims to provide a long-term solution by enabling the body to produce the necessary protein on its own.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on antiviral therapy for hepatitis B or C, you may not be eligible to participate.

What data supports the effectiveness of the treatment ASC618 for Hemophilia A?

Gene therapy for hemophilia A, like ASC618, shows promise because similar treatments using adeno-associated viral (AAV) vectors have been effective in increasing clotting factor levels and reducing bleeding episodes in patients. Other gene therapies for hemophilia have been approved based on their ability to significantly improve patients' conditions, suggesting potential for ASC618. ^{1 2 3 4 5}

Is gene therapy for hemophilia A safe for humans?

Gene therapy for hemophilia, using adeno-associated virus vectors, has been shown to be generally safe and well-tolerated in clinical trials for hemophilia B, with no major safety concerns reported. Some mild and temporary liver enzyme changes were observed, but these were manageable and did not lead to serious health issues. ^{5 6 7 8 9}

How is the treatment ASC618 unique for hemophilia A?

ASC618 is a gene therapy that aims to provide a long-term solution for hemophilia A by introducing a functional gene to produce factor VIII continuously, potentially reducing or eliminating the need for regular injections of clotting factors. ^{2 10 11 12 13}

Eligibility Criteria

This trial is for male adults over 18 with severe or moderately severe hemophilia A, experiencing at least 12 bleeding episodes a year if on-demand therapy. They must have used replacement therapy for over 150 days and have a BMI of ≤30. Participants need to commit to using double-barrier contraception post-treatment until semen tests are negative.

Inclusion Criteria

Agree to use double-barrier contraceptive until at least 3 consecutive semen samples are negative after ASC-618 infusion

BMI ≤ 30

I am a man aged 18 or older.

Exclusion Criteria

I am currently on medication for hepatitis B or C.

Evidence of active Hepatitis B, Hepatitis C, Human Immunodeficiency Virus (HIV)-1/2 or syphilis infection

I have or had high levels of Factor VIII inhibitors.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ASC618 gene therapy to evaluate safety and preliminary efficacy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• ASC618 (Gene Therapy)

Trial Overview The study is testing ASC618, an advanced gene therapy designed to deliver a corrected form of the factor VIII gene to patients with hemophilia A. The goal is to reduce the frequency of bleeding episodes and treatment injections by enabling sustained production of factor VIII in the body.

Participant Groups

Group I: ASC618 Experimental Treatment 1 Intervention

Experimental Arm

Who Is Running the Clinical Trial?

ASC Therapeutics

Lead Sponsor

Trials

2

Recruited

70+

Findings from Research

Gene therapies like Roctavian® and Hemgenix® have been approved for treating severe hemophilia A and B, respectively, showing significant increases in clotting factor levels and reductions in bleeding episodes based on phase III clinical trial data.

While most patients experienced short-term liver inflammation that was manageable with immune suppression, there remains variability in treatment response, and further research is needed to determine the long-term stability of factor expression and the potential for a permanent cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophilia Gene Therapy: The End of the Beginning? De Wolf, D., Singh, K., Chuah, MK., et al.[2023]

A single injection of a helper-dependent adenoviral vector (HDV) in three hemophilia A dogs resulted in significant improvements in blood clotting measures, with two dogs achieving near-normal clotting times and no bleeding events reported after treatment.

While there were transient increases in liver enzymes and thrombocytopenia following the injection, these side effects resolved within two weeks, indicating that the treatment is generally safe despite some initial toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helper-dependent adenoviral gene therapy mediates long-term correction of the clotting defect in the canine hemophilia A model. McCORMACK, WM., Seiler, MP., Bertin, TK., et al.[2023]

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]

Gene therapy for haemophilia B has shown promising results, with a single intravenous treatment leading to a long-term increase in therapeutic levels of factor IX (FIX) for over 4 years without significant toxicity.

This approach offers a potential cure compared to traditional clotting factor replacement therapy, which is costly and requires lifelong administration, but challenges remain before gene therapy can be widely implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemophilia gene therapy: Progress and challenges. Lheriteau, E., Davidoff, AM., Nathwani, AC.[2022]

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]

Gene therapy for hemophilia aims to improve or cure the condition by increasing levels of deficient coagulation factors through the use of liver-directed adeno-associated viral vectors, with several programs currently in phase 3 trials.

There is a critical need for long-term data collection on the safety and efficacy of these gene therapies, which is being coordinated by organizations like the American Thrombosis and Hemostasis Network and the World Federation of Hemophilia to ensure optimal treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The critical need for postmarketing surveillance in gene therapy for haemophilia. Konkle, BA., Recht, M., Hilger, A., et al.[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]

In a study involving 10 adults with severe hemophilia B, a single infusion of the gene therapy AMT-060 led to significant increases in endogenous factor IX (FIX) activity, with mean levels reaching 4.4 IU/dL in the low-dose group and 6.9 IU/dL in the high-dose group, resulting in an 81% and 73% reduction in FIX concentrate use, respectively.

The therapy demonstrated a positive safety profile, with only limited and transient elevations in liver enzymes that were asymptomatic and manageable, while effectively reducing spontaneous bleeding rates by 53% and 70% in the respective dose cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Miesbach, W., Meijer, K., Coppens, M., et al.[2021]

Gene transfer has shown promise as a safe and well-tolerated treatment for hemophilia A and B, based on results from four completed phase I clinical trials and two ongoing trials.

Current research is focused on enhancing the efficiency of gene transfer techniques to improve treatment outcomes for patients with hemophilia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophilia gene therapy: update. Monahan, PE., White, GC.[2019]

Recent advancements in hemophilia treatment include monoclonal antibodies that mimic factor VIII activity, providing effective therapy for all hemophilia A phenotypes, including those with inhibitors, and improving patient quality of life with safer and longer-lasting effects.

Gene therapy, particularly using CRISPR/Cas technology, shows promise for potentially curing hemophilia by permanently editing genes, with ongoing developments aimed at minimizing risks and enhancing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Therapies in Hemophilia: From Plasma-Derived Factor Modalities to CRISPR/Cas Alternatives. Jair Lara-Navarro, I., Rebeca Jaloma-Cruz, A.[2022]

Gene therapy for hemophilia aims to cure the condition by providing a functional copy of the defective gene responsible for producing blood clotting factors, which can significantly reduce bleeding episodes with just a small increase in factor levels (≥2% of normal).

Recent trials, including seven early-phase studies involving over 55 patients with hemophilia A and B, have shown promising results, indicating that gene therapy is moving closer to market authorization as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Gene Therapy for Hemophilia. Nathwani, AC., Davidoff, AM., Tuddenham, EGD.[2018]

Gene therapy for hemophilia, specifically with products like valoctocogene roxaparvovec for hemophilia A and etranacogene dezaparvovec for hemophilia B, is nearing approval and represents a significant advancement in treatment, allowing for a one-time infusion that leads to the body's own production of missing clotting factors.

Clinical observations indicate that gene therapy can provide sustained benefits for over 5 years after a single treatment, with manageable side effects such as temporary increases in liver enzymes, suggesting a promising safety profile for these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for hemophilia. Nathwani, AC.[2023]

Gene therapy for hemophilia A and B has shown promising results in preclinical studies, achieving long-term correction of bleeding disorders in animal models using viral vectors.

Phase I clinical trials in humans with severe hemophilia A or B are underway, and preliminary data suggest that gene therapy could potentially provide a cure, marking a significant advancement in treatment options for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral vector-mediated gene therapy for hemophilia. VandenDriessche, T., Collen, D., Chuah, MK.[2019]

References

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

Hemophilia Gene Therapy: The End of the Beginning? [2023]

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

Helper-dependent adenoviral gene therapy mediates long-term correction of the clotting defect in the canine hemophilia A model. [2023]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Haemophilia gene therapy: Progress and challenges. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

The critical need for postmarketing surveillance in gene therapy for haemophilia. [2021]

7. 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]

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

Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. [2021]

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

Hemophilia gene therapy: update. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

Current Therapies in Hemophilia: From Plasma-Derived Factor Modalities to CRISPR/Cas Alternatives. [2022]

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

Advances in Gene Therapy for Hemophilia. [2018]

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

Gene therapy for hemophilia. [2023]

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

Viral vector-mediated gene therapy for hemophilia. [2019]