Gene Therapy for Hemophilia B

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a gene therapy for adults with Hemophilia B. The therapy aims to help their bodies produce a missing protein needed for blood clotting by delivering a healthy gene to their liver cells. Gene therapy for hemophilia B has shown promise in previous studies.

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.

What data supports the effectiveness of the treatment AskBio009 for Hemophilia B?

Research shows that gene therapy using viral vectors can lead to sustained levels of clotting factor activity, reducing bleeding in hemophilia B patients. A specific study reported that a similar gene therapy approach resulted in near elimination of bleeding for over a year without serious side effects. ^{1 2 3 4 5}

Is gene therapy for Hemophilia B safe for humans?

Gene therapy for Hemophilia B, including treatments like AskBio009, has shown a favorable safety profile in clinical trials, with no serious side effects reported and a reduction in bleeding episodes. Studies have demonstrated sustained factor IX levels without significant adverse effects, making it a promising option for patients. ^{1 3 6 7 8}

How is the treatment AskBio009 for hemophilia B different from other treatments?

AskBio009 is a gene therapy that uses a single injection to deliver a working copy of the F9 gene, potentially providing long-lasting protection against bleeding, unlike standard treatments that require frequent enzyme-replacement injections. ^{1 4 9 10 11}

Research Team

Study Director

Principal Investigator

Shire

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Viral vector-mediated gene therapy for hemophilia B. [2012]

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

Adenovirus mediated expression of therapeutic plasma levels of human factor IX in mice. [2012]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Gene Therapy Approaches for the Treatment of Hemophilia B. [2023]

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

Gene therapy for hemophilia: advancing beyond the first clinical success. [2014]

6. 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]

7. Germany pubmed.ncbi.nlm.nih.gov

[Non-viral gene transfer results in therapeutic factor IX levels in haemophilia B mice]. [2008]

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

Long-term safety and efficacy of factor IX gene therapy in hemophilia B. [2022]

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

Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. [2023]

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

Preclinical and clinical progress in hemophilia gene therapy. [2012]

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

Advances in Gene Therapy for Hemophilia. [2018]