Factor IX Gene Therapy for Hemophilia B

(BENEGENE-2 Trial)

Not currently recruiting at 80 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gene therapy treatment called PF-06838435 for adult men with hemophilia B, a condition where blood doesn't clot properly. The goal is to determine if this treatment can safely reduce bleeding episodes by correcting the missing or non-working Factor IX in their blood. Participants must have been on Factor IX therapy for at least six months and have a specific level of Factor IX activity in their blood. Those managing hemophilia B with regular Factor IX treatments might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that PF-06838435 is likely to be safe for humans?

Research shows that fidanacogene elaparvovec, the gene therapy under study, appears safe. In earlier studies, patients with hemophilia B who received this treatment experienced fewer bleeding episodes and maintained stable levels of Factor IX, a protein that aids blood clotting. This suggests the therapy could be safe and well-tolerated.

In one study, 15 patients received the gene therapy and were monitored for at least a year. The results showed no serious side effects from the treatment. Another study found that Factor IX levels increased and remained stable for 24 months, with no major safety issues.

Overall, these findings suggest that the gene therapy may be safe for people based on current evidence. However, like any treatment, ongoing research will continue to assess its safety. ^{1 2 3 4 5}

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

Unlike standard treatments for Hemophilia B, which often require regular infusions of clotting factor IX, PF-06838435 is a one-time gene therapy. This unique approach uses fidanacogene elaparvovec to deliver a functional copy of the factor IX gene directly into the patient's liver cells, enabling them to produce factor IX on their own. Researchers are excited about this treatment because it has the potential to significantly reduce or even eliminate the need for ongoing factor IX infusions, offering a long-term solution with just a single administration.

What evidence suggests that this gene therapy might be an effective treatment for hemophilia B?

Research shows that the gene therapy PF-06838435, also known as fidanacogene elaparvovec, offers promising results for treating hemophilia B. In earlier studies, this treatment outperformed regular Factor IX replacement therapy, reducing bleeding incidents and maintaining stable Factor IX levels. Follow-up data revealed a significant drop in bleeding rates, from an average of 11.1 events to much lower numbers. Additionally, the therapy increased Factor IX activity to levels seen in mild hemophilia or even normal ranges. These findings suggest that PF-06838435 could be an effective option for people with moderately severe to severe hemophilia B. ^{1 2 3 4 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39321362/

Gene Therapy with Fidanacogene Elaparvovec in Adults ... Fidanacogene elaparvovec was superior to prophylaxis for the treatment of participants with hemophilia B, leading to reduced bleeding and stable factor IX ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03861273

NCT03861273 | A Study to Evaluate the Efficacy and ... This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B

3. bleeding.org bleeding.org/news/nejm-publishes-follow-up-data-on-hemophilia-b-gene-therapy-product

Follow-up Trial Data on Hemophilia B Gene Therapy Now ... During the follow-up, mean factor IX activity was in the mild hemophilia range, as mean annualized bleeding rates were reduced from 11.1 events ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3577/529708/Use-of-Fidanacogene-Elaparvovec-a-Gene-Therapy

Use of Fidanacogene Elaparvovec, a Gene Therapy Vector, to ... In the ongoing, phase 3 BENEGENE-2 trial, fidanacogene elaparvovec resulted in FIX activity levels in the mild hemophilia to normal range and a ...

5. pfizer.com pfizer.com/sites/default/files/plsr-studies/C0371002%20Plain%20Language%20Study%20Results%20Summary%20%28PLSRS%29%20Phase%202-4.pdf

Clinical Study Results The researchers wanted to learn if the treatment with fidanacogene elaparvovec was not less effective than the current routine FIX replacement ...

6. genetherapy.isth.org genetherapy.isth.org/education/conference-coverage/highlights-from-the-32nd-congress-of-isth/efficacy-and-safety-of-fidanacogene-elaparvovec

Conference Coverage - Gene Therapy for Hemophilia FIX levels rose to a mean of 27.8% at 12 weeks and remained stable through month 24 as measured by a one-stage SynthASil assay.