Gene Therapy for Hemophilia A

(AFFINE Trial)

Not currently recruiting at 45 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18 - 65

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Factor VIII

Disqualifiers: Liver disease, Thrombophilia, Hepatitis, 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: 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, PF-07055480 (giroctocogene fitelparovec), for men with moderately severe to severe hemophilia A, a condition that hinders proper blood clotting. The goal is to determine if a single infusion of the experimental treatment can safely and effectively reduce the need for regular clotting-factor treatments. Eligible participants must have been on routine clotting treatment and have a history of using Factor VIII products. As a Phase 3 trial, this represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for hemophilia A.

Will I have to stop taking my current medications?

Yes, participants will need to stop their routine Factor VIII prophylaxis therapy after receiving the study drug infusion.

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

Research has shown that giroctocogene fitelparvovec has been tested for safety in people with hemophilia A. Early results from a study that tracked participants for at least two years showed encouraging safety outcomes. Most side effects related to the treatment were mild. A common issue was a temporary increase in liver enzymes, which doctors monitored and managed. This gene therapy uses a type of virus that has not caused serious safety problems in these studies.

Prospective trial participants can find reassurance in these findings. However, discussing potential risks with a healthcare provider remains important, as with any medical treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Hemophilia A, which typically involve regular infusions of clotting factor VIII, giroctocogene fitelparvovec is a gene therapy that aims to provide a long-term solution with just a single administration. This therapy works by delivering a functional copy of the gene responsible for producing factor VIII directly into the patient's liver cells, potentially allowing the body to produce its own clotting factor naturally. Researchers are excited about this approach because it could significantly reduce or even eliminate the need for frequent infusions, offering a more convenient and potentially more effective treatment option.

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

Research has shown that giroctocogene fitelparvovec, the investigational treatment in this trial, offers promising results for treating hemophilia A. In one study, patients who received this gene therapy experienced a significant increase in their Factor VIII levels, crucial for blood clotting. This therapy aims to reduce bleeding by helping the body produce more of this vital protein. Specifically, previous patients managed their condition better, with fewer bleeding episodes and less need for additional treatments. These findings suggest that giroctocogene fitelparvovec could be an effective option for people with severe hemophilia A. ^{1 2 3 5 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 A (Factor VIII activity ≤1%) who have been on routine Factor VIII prophylaxis and participated in the lead-in study C0371004 with ≥150 exposure days to a Factor VIII product. Excluded are those with anti-AAV6 antibodies, history of Factor VIII inhibitors, abnormal lab values, thrombosis risk, planned surgeries requiring prophylaxis within 12 months, active hepatitis B or C, significant HIV infection or liver disease.

Inclusion Criteria

I am a male with >= 150 days of Factor VIII treatment from the C0371004 study.

My hemophilia A is classified as moderately severe to severe.

I will stop my FVIII treatments after starting the study drug.

Exclusion Criteria

Anti-AAV6 neutralizing antibodies

History of inhibitor to Factor VIII

Abnormal or outside acceptable study limits laboratory values at screening visit

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single IV infusion of PF-07055480 / giroctocogene fitelparvovec gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Yearly assessments

What Are the Treatments Tested in This Trial?

Interventions

• PF-07055480 (giroctocogene fitelparovec)

Trial Overview The trial is testing PF-07055480 (giroctocogene fitelparvovec), a gene therapy delivered through a single IV infusion aimed at treating hemophilia A. The efficacy and safety will be monitored over five years in participants who suspend their usual FVIII prophylaxis post-infusion.

How Is the Trial Designed?

Group I: PF-07055480 (giroctocogene fitelparvovec) Experimental Treatment 1 Intervention

Single administration of PF-07055480

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

Etranacogene dezaparvovec, a gene therapy for hemophilia, has shown the ability to provide sustained factor IX expression for over 2 years, potentially allowing most patients to live without bleeding episodes or the need for infusions.

The therapy utilizes a specific adeno-associated virus vector and has demonstrated promising efficacy and safety in clinical trials, making it a significant advancement in hemophilia treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etranacogene dezaparvovec for hemophilia B gene therapy. Thornburg, CD.[2023]

Gene therapies like Roctavian® and Hemgenix® have been approved for treating severe hemophilia A and B, respectively, showing significant increases in clotting factor levels and reductions in bleeding episodes based on phase III clinical trial data.

While most patients experienced short-term liver inflammation that was manageable with immune suppression, there remains variability in treatment response, and further research is needed to determine the long-term stability of factor expression and the potential for a permanent cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophilia Gene Therapy: The End of the Beginning? De Wolf, D., Singh, K., Chuah, MK., et al.[2023]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-results-phase-3-study

Pfizer Announces Positive Topline Results From Phase 3 ... Pfizer Inc. (NYSE: PFE) today announced positive topline results from the Phase 3 AFFINE study ( NCT04370054 ) evaluating giroctocogene fitelparvovec.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04370054

Study to Evaluate the Efficacy and Safety of PF-07055480 ... C3731003 is a pivotal Phase 3 study to evaluate the clinical efficacy and safety of a single IV infusion of PF-07055480 / giroctocogene fitelparvovec ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10933705/

Giroctocogene fitelparvovec gene therapy for severe ... Leavitt and colleagues report on the 2-year outcomes of gene therapy for hemophilia A with giroctocogene fitelparvovec, an adeno-associated virus vector ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1053/530509/Efficacy-and-Safety-of-Giroctocogene-Fitelparvovec

Efficacy and Safety of Giroctocogene Fitelparvovec in Adults ... We present results from the primary analysis of an ongoing pivotal phase 3 study to evaluate the efficacy and safety of giroctocogene fitelparvovec in ...

5. investor.sangamo.com investor.sangamo.com/static-files/45bcb0da-9135-41f8-93ef-407f91ba2085

Efficacy and Safety of Giroctocogene Fitelparvovec in ... Plain Language Study Results Summaries are descriptions in everyday language of the design and results of clinical studies. These summaries ( ...

6. sangamo.com sangamo.com/programs/clinical-trials/hemophilia-a/

Hemophilia A Hemophilia A is a rare bleeding disorder caused by mutations in the F8 gene, resulting in a deficiency of clotting factor VIII (FVIII).