CSL222 Gene Therapy for Hemophilia B

Recruiting at 17 trial locations

Overseen By Trial Registration Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: CSL Behring

Must be taking: FIX prophylaxis

Must not be taking: Oral corticosteroids

Disqualifiers: Severe hepatic impairment, Thrombocytopenia, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

35 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, you must have been on stable FIX prophylaxis for at least 2 months before screening.

What data supports the effectiveness of the treatment CSL222 for Hemophilia B?

Research shows that etranacogene dezaparvovec, a gene therapy for Hemophilia B, provides sustained production of factor IX (a protein needed for blood clotting) for more than 2 years, reducing the need for regular treatments and preventing bleeding in most patients. ^{1 2 3 4 5}

What makes the treatment CSL222 unique for hemophilia B?

CSL222, also known as Etranacogene dezaparvovec, is unique because it is the first gene therapy approved for hemophilia B, offering a potential long-term solution by using a virus to deliver a healthy version of the gene responsible for producing factor IX, which is missing or defective in patients with this condition. ^{1 2 3 5 6}

What is the purpose of this trial?

The purpose of this study is to assess the risk of bleeding due to failure of expected pharmacological action of CSL222 in adults with severe or moderately severe hemophilia B with detectable pretreatment AAV5 Nabs.

Research Team

Study Director

Principal Investigator

CSL Behring

Eligibility Criteria

Adults with severe or moderately severe hemophilia B who have been on stable clotting factor IX (FIX) prophylaxis, and have detectable AAV5 neutralizing antibodies. Participants must have had over 150 days of prior FIX therapy and be able to use eDiaries correctly. They should agree to use barrier contraception for a year post-treatment and not have any history of FIX inhibitors, severe liver impairment, uncontrolled infections like HIV or hepatitis C, thrombocytopenia, allergies to steroids or CSL222 components, previous gene therapy treatments, or other conditions causing increased bleeding.

Inclusion Criteria

I have severe or moderately severe hemophilia B and am on regular treatment.

Acceptance to barrier contraception protection for 1 year starting the day of CSL222 treatment

I have been treated with FIX therapy for more than 150 days.

Exclusion Criteria

I have had inhibitors to Factor IX or tested positive for them.

ALT > 2 × the upper limit of normal (ULN) at Screening and Visit L-Final (based on central laboratory results)

I have a condition that makes me bleed more easily, but it's not hemophilia B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous (IV) infusion of CSL222 gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Regular visits (frequency not specified)

Treatment Details

Interventions

• CSL222

Trial Overview The trial is testing the safety and effectiveness of CSL222 (Etranacogene Dezaparvovec), a gene therapy in adults with hemophilia B who already have AAV5 neutralizing antibodies. The goal is to see if this treatment can reduce the risk of bleeding by providing a functional version of the FIX gene.

Participant Groups

Group I: CSL222 Experimental Treatment 1 Intervention

Participants will receive CSL222 as a single intravenous (IV) infusion of 2 × 10\^13 genome copies per kilogram (gc/kg) on Day 1.

CSL222 is already approved in European Union, United States for the following indications:

Approved in European Union as HEMGENIX for:

• Hemophilia B

Approved in United States as HEMGENIX for:

• Hemophilia B

Who Is Running the Clinical Trial?

CSL Behring

Lead Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

Findings from Research

Etranacogene dezaparvovec is the first approved gene therapy for adults with severe and moderately severe hemophilia B, allowing most patients to achieve stable factor IX levels after a single infusion, which significantly reduces the need for regular treatment and associated bleeding risks.

The therapy has shown efficacy even in patients with preexisting neutralizing antibodies and has a relatively low risk of transaminitis, but long-term data is needed to confirm the durability of factor IX levels and overall safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etranacogene dezaparvovec for the treatment of adult patients with severe and moderately severe hemophilia B. Castaman, G., Coppens, M., Pipe, SW.[2023]

Etranacogene dezaparvovec (Hemgenix®) is a gene therapy approved in the USA for treating adults with hemophilia B, specifically for those on FIX prophylaxis or with serious bleeding episodes.

The therapy received a positive opinion in the EU in December 2022, marking significant progress in its development and approval for treating congenital factor IX deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etranacogene Dezaparvovec: First Approval. Heo, YA.[2023]

Valoctocogene roxaparvovec (Roctavian) and etranacogene dezaparavovec (Hemgenix) are effective gene therapies for hemophilia A and B, respectively, with phase 3 studies showing significant increases in clotting factor levels and reductions in bleeding events among participants (n=134 for Roctavian and n=54 for Hemgenix).

Both therapies were associated with manageable safety profiles, primarily involving elevated liver function tests, and they improved patients' quality of life by mimicking natural clotting factor production, offering a promising alternative to traditional replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valoctocogene Roxaparvovec and Etranacogene Dezaparavovec: Novel Gene Therapies for Hemophilia A and B. Dougherty, JA., Dougherty, KM.[2023]

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]

Etranacogene dezaparvovec gene therapy for hemophilia B shows promising long-term durability, with predictions indicating that over 80% of participants could remain free from prophylactic FIX replacement for up to 25.5 years after a single treatment.

Statistical modeling of FIX activity levels suggests that only about 10.91% of participants would have FIX activity levels below 2% over the same period, indicating sustained effectiveness of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B. Shah, J., Kim, H., Sivamurthy, K., et al.[2023]

Etranacogene dezaparvovec-drlb (Hemgenix) is an FDA-approved gene therapy for congenital hemophilia B that provides stable and sustained expression of near-normal Factor IX levels, significantly reducing bleeding episodes and the need for prophylactic FIX infusions.

The therapy was well tolerated overall, although 17% of patients experienced elevated alanine aminotransferase (ALT) levels and required corticosteroid treatment, highlighting the need for monitoring liver function post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etranacogene dezaparvovec-drlb gene therapy for patients with hemophilia B (congenital factor IX deficiency). Sekayan, T., Simmons, DH., von Drygalski, A.[2023]

References

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

Etranacogene dezaparvovec for the treatment of adult patients with severe and moderately severe hemophilia B. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Etranacogene Dezaparvovec: First Approval. [2023]

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

Valoctocogene Roxaparvovec and Etranacogene Dezaparavovec: Novel Gene Therapies for Hemophilia A and B. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Etranacogene dezaparvovec for hemophilia B gene therapy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B. [2023]

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

Etranacogene dezaparvovec-drlb gene therapy for patients with hemophilia B (congenital factor IX deficiency). [2023]