Factor IX Gene Therapy for Hemophilia B

(BENEGENE-2 Trial)

Recruiting at 67 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Factor IX

Must not be taking: Aspirin, Ibuprofen, Antivirals, others

Disqualifiers: Chronic infection, Liver disease, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

51 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop their current Factor IX prophylaxis therapy after receiving the study drug. The protocol does not specify about other medications, but certain therapies like blood products, aspirin, ibuprofen, and other investigational therapies are restricted.

What data supports the effectiveness of the treatment PF-06838435 for hemophilia B?

Research shows that gene therapy using modified versions of factor IX can significantly increase its activity, leading to better blood clotting in hemophilia B. Studies in animals and humans have demonstrated that these gene therapies can produce stable and long-term expression of factor IX, improving clotting times without significant side effects. ^{1 2 3 4 5}

Is Factor IX gene therapy for hemophilia B safe for humans?

Factor IX gene therapy for hemophilia B has shown a positive safety profile in several studies. In trials with humans and animals, there were no significant side effects, no evidence of toxicity, and no immune responses against the treatment. Some participants experienced mild, temporary liver enzyme changes, which were managed with medication. ^{2 6 7 8 9}

How is the treatment PF-06838435 for hemophilia B different from other treatments?

PF-06838435 is a gene therapy that aims to provide a long-term solution for hemophilia B by inserting a factor IX gene into the patient's cells, allowing them to produce their own factor IX, unlike traditional treatments that require frequent injections of factor IX concentrates. ^{1 5 10 11 12}

What is the purpose of this trial?

This trial tests a new gene therapy treatment for adult men with severe hemophilia B. The treatment aims to help their bodies produce a crucial blood-clotting protein. Participants will receive one dose and be monitored over several years to see if it reduces their bleeding episodes. Gene therapy for hemophilia B has shown promising results in recent studies, suggesting potential long-term therapeutic production of the coagulant protein.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

Adult males with moderately severe to severe hemophilia B (Factor IX activity <=2%) who have completed at least 6 months of Factor IX prophylaxis therapy. Participants must not have antibodies against the gene therapy vector, no history of Factor IX inhibitors, and agree to contraception post-treatment.

Inclusion Criteria

Laboratory values (hemoglobin, platelets and creatinine) within study specified limits

My hemophilia B is severe with Factor IX activity at 2% or less.

I will stop my preventive hemophilia B treatment after starting the study drug.

Exclusion Criteria

I am not currently using any restricted medications like aspirin, ibuprofen, or experimental drugs.

Study and sponsor staff and their families involved in the conduct of the study

Laboratory values at screening visit that are abnormal or outside acceptable study limits

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-infusion

Participants receive at least 6 months of routine Factor IX prophylaxis therapy

6 months

Treatment

Participants receive a single intravenous dose of the gene therapy drug PF-06838435

1 day

Post-infusion Monitoring

Participants are monitored for safety and effectiveness, with assessments from Week 12 to Month 15

15 months

Long-term Follow-up

Participants are monitored for long-term safety and efficacy outcomes

6 years

Treatment Details

Interventions

• PF-06838435

Trial Overview The trial is testing PF-06838435, a gene therapy intended to correct the genetic defect in hemophilia B by providing a functional copy of the Factor IX gene. Patients will receive one intravenous dose and be monitored over six years against standard prophylactic treatment.

Participant Groups

Group I: PF-06838435/ fidanacogene elaparvovec Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Towards gene therapy for hemophilia B. [2007]

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

Bioengineered factor IX molecules with increased catalytic activity improve the therapeutic index of gene therapy vectors for hemophilia B. [2021]

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

Factor IX variants improve gene therapy efficacy for hemophilia B. [2021]

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

Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. [2022]

5. China pubmed.ncbi.nlm.nih.gov

Expression of human factor IX cDNA in mice by implants of genetically modified skin fibroblasts from a hemophilia B patient. [2006]

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

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

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

Technology evaluation: AAV factor IX gene therapy, Avigen Inc. [2012]

8. 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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Alprolix (recombinant Factor IX Fc fusion protein): extended half-life product for the prophylaxis and treatment of hemophilia B. [2018]

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

Advances toward gene therapy for hemophilia at the millennium. [2012]

12. China pubmed.ncbi.nlm.nih.gov

Stage I clinical trial of gene therapy for hemophilia B. [2012]