Gene Therapy for Hemophilia B

Not currently recruiting at 14 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Baxalta now part of Shire

Must be taking: Factor IX

Disqualifiers: Hepatitis C, Cirrhosis, 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 tests a new gene therapy treatment called AskBio009 for individuals with Hemophilia B, a condition that prevents proper blood clotting and causes frequent bleeding. The main goal is to determine the safety of this treatment at different doses. The trial seeks men aged 18-75 who experience frequent bleeding episodes due to Hemophilia B and require regular clotting treatments. Participants should not have active Hepatitis C or a history of certain liver problems. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the safety of AskBio009, a gene therapy for Hemophilia B, has been tested in earlier studies. In one study, 10 patients with severe Hemophilia B received a single dose of the therapy, which includes the AAV8 vector. These patients experienced long-lasting benefits in their factor IX levels, aiding blood clotting.

The therapy was generally well-tolerated, indicating safety for most individuals. No serious side effects were directly linked to the treatment. Some patients experienced mild side effects, but these were manageable. Another study confirmed that a similar gene therapy, etranacogene dezaparvovec, remained safe over three years.

These findings suggest that the treatment is relatively safe, but ongoing trials continue to confirm its safety and effectiveness. ^{1 2 3 4 5}

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

Unlike the standard of care for Hemophilia B, which often involves regular infusions of clotting factor IX, AskBio009 offers a potentially transformative approach through gene therapy. This treatment uses a unique mechanism where a single dose of an optimized adeno-associated virus (AAV) delivers the factor IX gene directly into the body. Researchers are excited because this could lead to sustained production of factor IX, reducing or even eliminating the need for frequent infusions and offering a long-term solution for patients.

What evidence suggests that this gene therapy could be an effective treatment for Hemophilia B?

Research shows that gene therapy for Factor IX (FIX) holds promise for treating hemophilia B. Studies have found that a single dose of a virus carrying the FIX gene can maintain FIX at therapeutic levels in the blood for an extended period. Specifically, patients with severe hemophilia B experienced lasting increases in FIX levels after receiving this therapy. This trial will evaluate AskBio009, which uses a similar method, to determine its effectiveness in raising FIX levels and controlling bleeding in people with hemophilia B. Early trials indicate that this treatment could significantly improve normal blood clotting. ^{1 3 4 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 adult males aged 18-75 with Hemophilia B, experiencing frequent bleeding episodes or requiring regular treatment. Participants must have low plasma FIX activity and no history of inhibitors to FIX protein. They should not have Hepatitis C, detectable AAV8 antibodies, significant liver inflammation, cirrhosis signs, or allergies to any FIX product.

Inclusion Criteria

I do not have an active Hepatitis C infection.

I have hemophilia B and need treatment often due to frequent bleeding.

I am a man aged between 18 and 75.

Exclusion Criteria

I have a family history or personal evidence of inhibitors to the FIX protein.

I have signs of liver problems or damage.

Detectable AAV8 neutralizing antibodies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single ascending IV dose of the Factor IX Gene Therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, kinetics, and plasma FIX activity levels after treatment

12 months

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• AskBio009

Trial Overview The study tests the safety of different doses of AskBio009, a gene therapy delivered through IV aiming to treat Hemophilia B by providing a functional copy of the Factor IX gene responsible for blood clotting.

How Is the Trial Designed?

Group I: AskBio009 Dose Escalation Experimental Treatment 1 Intervention

Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy

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

Published Research Related to This Trial

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]

Gene therapy for hemophilia B, using a single injection of adeno-associated viral (AAV) vectors, can restore and maintain F9 gene expression for a much longer duration compared to standard enzyme-replacement therapy, which requires frequent administration.

Research is ongoing to enhance the efficiency of gene delivery and expression, as well as exploring CRISPR/Cas9 technology for potential genome editing as a treatment option for hemophilia B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene Therapy Approaches for the Treatment of Hemophilia B. Soroka, AB., Feoktistova, SG., Mityaeva, ON., et al.[2023]

AAV-mediated gene therapy for hemophilia B demonstrated sustained levels of factor IX (FIX) in patients, resulting in the near elimination of bleeding episodes for over a year.

The treatment was well-tolerated, with no serious adverse side effects reported, marking it as the most successful outcome for hemophilia gene therapy to date.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FIX It in One Go: Enhanced Factor IX Gene Therapy for Hemophilia B. Lillicrap, D.[2019]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1407309

Long-Term Safety and Efficacy of Factor IX Gene Therapy ... Conclusions. In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7885820/

BAX 335 hemophilia B gene therapy clinical trial results Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 ...

3. researchgate.net researchgate.net/publication/295798564_A_Phase_12_open-label_trial_of_an_adeno-associated_virus_AAV_serotype_8_factor_IX_gene_therapy_AskBio009_in_adults_with_hemophilia_B

A Phase 1/2 open-label trial of an adeno-associated virus ... A Phase 1/2 open-label trial of an adeno-associated virus (AAV) serotype 8 factor IX gene therapy (AskBio009) in adults with hemophilia B.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25409372/

Long-term safety and efficacy of factor IX gene therapy in ... Conclusions: In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX ...

5. ashpublications.org ashpublications.org/bloodadvances/article/8/23/5957/518100/Adeno-associated-virus-based-gene-therapy-for

Adeno-associated virus–based gene therapy for hemophilia A ... For HB, efficacy outcomes additionally covered factor usage and factor levels at 12 months. Safety outcomes for HB mirrored those of HA.

6. ashpublications.org ashpublications.org/bloodadvances/article/7/19/5671/493567/Stable-and-durable-factor-IX-levels-in-patients

Stable and durable factor IX levels in patients with hemophilia ... Etranacogene dezaparvovec was safe and effective in adults with hemophilia B over 3 years after administration.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01687608

Open-Label Single Ascending Dose of Adeno-associated ... The purpose of this study is to evaluate the safety of single ascending IV doses of a Factor IX (FIX) Gene Therapy in up to 16 Adults with Hemophilia B.