CSL222 Gene Therapy for Hemophilia B

Recruiting at 32 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called CSL222 for individuals with hemophilia B, a condition that prevents proper blood clotting and causes severe bleeding. The goal is to determine if CSL222 can reduce bleeding risks in those with severe forms of this condition. Participants should have a history of severe hemophilia B, be on regular preventive treatment, and be familiar with using an eDiary to track their health. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to help bring a potentially life-changing treatment to market.

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.

Is there any evidence suggesting that CSL222 is likely to be safe for humans?

Research has shown that CSL222, related to the treatment etranacogene dezaparvovec, has been safe in past studies. One study found this treatment remained effective and well-tolerated five years after use in adults with hemophilia B. Another study confirmed its safety and effectiveness in men with severe or moderately severe hemophilia B. These results suggest that the treatment is generally safe, with few serious side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for Hemophilia B, which often involves regular infusions of clotting factor IX, CSL222 is a gene therapy that offers a potentially long-lasting solution. Researchers are excited because CSL222 uses a single intravenous infusion to deliver a healthy copy of the gene responsible for producing factor IX directly into the patient's body. This innovative approach aims to enable the patient's own cells to produce the clotting factor, potentially reducing or even eliminating the need for frequent infusions. If successful, CSL222 could transform Hemophilia B management by offering a more convenient and enduring treatment option.

What evidence suggests that CSL222 might be an effective treatment for hemophilia B?

Research has shown that CSL222, a gene therapy for hemophilia B, might be effective. CSL222, also known as etranacogene dezaparvovec, has demonstrated safety and efficacy in individuals with severe or moderately severe hemophilia B, with positive results persisting even five years after administration. This therapy provides a healthy version of the gene needed for blood clotting, reducing the risk of bleeding. Early results also suggest that its benefits endure over time. Although rare instances exist where the treatment might not work, the overall evidence supports its potential to help those with hemophilia B. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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-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]

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 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 (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]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/14/3543/536584/Completion-of-phase-2b-trial-of-etranacogene

Completion of phase 2b trial of etranacogene dezaparvovec ... Five years after administration, etranacogene dezaparvovec was effective in adults with hemophilia B with a favorable safety profile.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40188458/

Completion of phase 2b trial of etranacogene ... Five years after administration, etranacogene dezaparvovec was effective in adults with hemophilia B with a favorable safety profile.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2211644

Gene Therapy with Etranacogene Dezaparvovec for ... In our study, etranacogene dezaparvovec had a favorable safety and efficacy profile in men with severe or moderately severe hemophilia B, ...

4. newsroom.csl.com newsroom.csl.com/2025-02-07-CSL-Behrings-Gene-Therapy-HEMGENIX-R-etranacogene-dezaparvovec-drlb-Four-Years-Post-Infusion-Data-Continue-to-Show-Sustained-Efficacy-and-Safety-in-Adults-with-Hemophilia-B

CSL Behring's Gene Therapy HEMGENIX® (etranacogene ... HEMGENIX (etranacogene dezaparvovec-drlb) four years post-infusion data continue to show sustained efficacy and safety in adults with hemophilia B.

5. hemgenix.com hemgenix.com/hcp/about-hemgenix/long-term-data

Long-term Data *Two patients experienced lack of efficacy. One patient had the highest NAb titer of 1:3212, and 1 patient received ~10% of the planned dose.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06003387

Study Details | NCT06003387 | Efficacy and Safety of ... 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 ...