Gene Therapy for Hemophilia B

Recruiting at 7 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must be taking: Factor IX concentrates

Must not be taking: Antiviral therapy

Disqualifiers: Hepatitis, HIV, Liver dysfunction, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial 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 scAAV2/8-LP1-hFIXco for hemophilia B?

Research shows that the treatment scAAV2/8-LP1-hFIXco, a type of gene therapy, can lead to high levels of factor IX (a protein needed for blood clotting) in mice and nonhuman primates. This suggests it could be effective in treating hemophilia B by increasing factor IX levels in the body. ^{1 2 3 4 5}

Is gene therapy for Hemophilia B using scAAV2/8-LP1-hFIXco generally safe in humans?

Research on gene therapy for Hemophilia B using scAAV vectors shows promising results with no significant safety concerns reported in animal studies. Some studies noted transient liver damage, but no long-term harmful effects or immune responses were observed, suggesting it may be generally safe. ^{1 2 4 6 7}

How is the gene therapy treatment scAAV2/8-LP1-hFIXco unique for hemophilia B?

The gene therapy treatment scAAV2/8-LP1-hFIXco is unique because it uses a self-complementary adeno-associated virus (scAAV) to deliver a modified version of the human factor IX gene directly to liver cells, which helps produce the missing clotting factor more efficiently and with lower immune response compared to traditional treatments. ^{1 2 4 5 8}

What is the purpose of this trial?

The purpose of this study is to determine the safety of giving a normal factor IX gene to treat individuals who have an abnormal or no factor IX gene. Recruitment will be limited to adults (≥ 18 years) with a confirmed diagnosis of hemophilia B (HB), resulting from a missense mutation in the coagulation factor IX (FIX) gene or a nonsense mutation that has not been associated with an inhibitor. Only subjects who have no evidence of active hepatitis or anti-hFIX antibodies, and who have been treated/exposed to Factor IX concentrates for at least ten years and have had an average of 3 bleeding episodes per year requiring FIX administration will be enrolled. Patients will be recruited within the United States for treatment at St. Jude Children's Research Hospital, and patients will be recruited in England and other countries for treatment in London by our British collaborators.

Research Team

Ulrike Reiss, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

Adult males (18+) with severe Hemophilia B, treated with FIX products for over 10 years or have had at least 50 exposure days. Candidates must average a minimum of three bleeding episodes per year requiring FIX infusions and be free of inhibitors to FIX protein. They should not have active hepatitis, HIV infections under control are eligible, and must agree to use barrier contraception.

Inclusion Criteria

Able to give informed consent and comply with requirements of the trial

My family does not have a history of developing inhibitors.

I agree to use barrier contraception until 3 tests show no vector genomes.

Exclusion Criteria

Subjects who are unwilling to provide the required semen samples

Creatinine ≥ 1.5 mg/dl

Platelet count of <50 x 10^9/l

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a gene transfer using a self-complementary AAV vector to deliver the normal factor IX gene

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after gene transfer

15 years

Treatment Details

Interventions

• scAAV2/8-LP1-hFIXco

Trial Overview The trial is testing the safety of a gene transfer treatment using scAAV2/8-LP1-hFIXco vector in adults with Hemophilia B. It aims to provide a normal factor IX gene to those who lack it due to genetic mutations causing their condition.

Participant Groups

Group I: Group 1 Experimental Treatment 2 Interventions

All participants who meet the eligibility requirements. Intervention: Gene Transfer and drug (scAAV2/8-LP1-hFIXco).

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

University College, London

Collaborator

Trials

884

Recruited

38,770,000+

Hemophilia of Georgia, Inc.

Collaborator

Trials

2

Recruited

3,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

References

1. 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]

2. China pubmed.ncbi.nlm.nih.gov

Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX. [2018]

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

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

4. China pubmed.ncbi.nlm.nih.gov

Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B. [2018]

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

A new potent hFIX plasmid for hemophilia B gene therapy. [2019]

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

Complete and sustained phenotypic correction of hemophilia B in mice following hepatic gene transfer of a high-expressing human factor IX plasmid. [2023]

7. China pubmed.ncbi.nlm.nih.gov

Gene therapy for hemophilia B mediated by recombinant adeno-associated viral vector with hFIXR338A, a high catalytic activity mutation of human coagulation factor IX. [2016]

8. China pubmed.ncbi.nlm.nih.gov

[Preparation of rAAV2/hFIX and experimentally application to gene therapy for hemophilia B]. [2012]