BE-101 for Hemophilia B

Recruiting at 4 trial locations

Overseen By Be Biopharma

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Be Biopharma

Must be taking: Factor IX products

Disqualifiers: B-cell malignancy, Immunodeficiency, Thromboembolic, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BE-101 for adults with moderately severe to severe Hemophilia B, a condition where blood doesn't clot properly due to low levels of a protein called FIX. BE-101 uses CRISPR/Cas9 gene editing to help the patient's own cells produce FIX, potentially reducing bleeding episodes. The trial evaluates the safety and effectiveness of different doses of BE-101. Men with Hemophilia B who have been on regular FIX treatments and can handle study procedures might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how BE-101 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants should currently be receiving prophylaxis treatment, which suggests you may need to continue certain treatments. It's best to discuss this with the trial team.

Is there any evidence suggesting that BE-101 is likely to be safe for humans?

Research has shown that BE-101 has potential based on early tests. In a study with mice, BE-101 was tested for safety over 28 days and was generally well-tolerated, with no major problems reported. This suggests that BE-101 might be safe for humans, although results in animals don't always apply directly to humans.

BE-101 is now undergoing its first tests in humans, with close monitoring for any side effects. This Phase 1/2 trial aims to assess its safety and understand any risks. As this is an early stage of human testing, information on safety is limited, but the treatment has passed initial safety checks in earlier tests. Participants in the trial will help researchers learn more about its safety in humans. ^{1 2 3 4 5}

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

Unlike the standard treatments for Hemophilia B, which often involve regular infusions of clotting factor IX, BE-101 is a gene therapy approach. Researchers are excited about BE-101 because it aims to provide a long-term solution by delivering a functional copy of the factor IX gene directly to the patient's liver cells. This could potentially reduce or eliminate the need for frequent treatments, offering a more sustainable and convenient option. Additionally, BE-101 may lead to a more stable and consistent production of the clotting factor, reducing the risk of bleeding episodes.

What evidence suggests that BE-101 might be an effective treatment for Hemophilia B?

Research shows that BE-101, the investigational treatment in this trial, could be promising for hemophilia B. This therapy uses CRISPR/Cas9 gene editing to add the human FIX gene into a person's own cells. Early studies have shown that this method can help the body produce FIX, a protein missing or low in people with hemophilia B. BE-101 aims to maintain steady FIX levels and reduce bleeding over time. Initial findings suggest that once administered, BE-101 can continuously release FIX into the bloodstream, potentially offering a long-lasting solution for patients. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adult men (18+) with moderately severe to severe Hemophilia B, currently on prophylaxis treatment, who have had over 50 days of exposure to Factor IX products. Participants must be able to undergo leukapheresis and have good organ function.

Inclusion Criteria

I am a man over 18 with severe Hemophilia B.

I have used Factor IX products for more than 50 days before joining.

I am currently on preventive treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis Collection

Participants undergo leukapheresis collection to support BE-101 manufacturing

1 week

1 visit (in-person)

Treatment

Participants receive a single intravenous (IV) dose of BE-101

1 day

1 visit (in-person)

Monitoring

Participants are monitored for safety and clinical activity post administration

52 weeks

Regular visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BE-101

Trial Overview BE-101 is being tested in this study. It's a gene-edited cell therapy designed for one-time infusion into adults with Hemophilia B, aiming to continuously produce the blood clotting factor they lack.

How Is the Trial Designed?

Group I: Part 2 - Dose Expansion, Cohort 2a Adult Expansion, Optimal Dose Selected in Part 1 Dose Escalation Experimental Treatment 1 Intervention

Group II: Part 1 - Dose Escalation, Dose Level 3 Experimental Treatment 1 Intervention

Group III: Part 1 - Dose Escalation, Dose Level 2 Experimental Treatment 1 Intervention

Group IV: Part 1 - Dose Escalation, Dose Level 1 Experimental Treatment 1 Intervention

BE-101 is already approved in United States for the following indications:

Approved in United States as BE-101 for:

• Hemophilia B

Who Is Running the Clinical Trial?

Be Biopharma

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

A total of 3225 adverse event reports were analyzed for two chimeric antigen receptor T-cell therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel), revealing that cytokine release syndrome (52.2%) and neurotoxicity (27.2%) were the most common toxicities, often occurring within the first 10 days after treatment.

The study identified specific emerging safety signals, such as a higher risk of cardiomyopathies and gastrointestinal perforations associated with axi-cel, and hepatotoxicity and pupil disorders linked to tisa-cel, highlighting the need for ongoing monitoring of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database. Fusaroli, M., Isgrò, V., Cutroneo, PM., et al.[2022]

In a study of 1155 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) for inflammatory arthritis, 8.7% experienced adverse events (AEs) and 23.3% faced treatment failures, highlighting the importance of monitoring safety in real-world settings.

Patients treated with secukinumab had a significantly lower risk of developing AEs, while those on golimumab, secukinumab, and tocilizumab showed a reduced likelihood of treatment failure, suggesting these medications may offer better safety and efficacy profiles compared to others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study. Barbieri, MA., Cicala, G., Cutroneo, PM., et al.[2020]

The modified Bonn-Malmö-Protocol (MBMP) effectively treats high-titer acquired hemophilia patients with severe bleeding, achieving a complete response rate of 93% within the first year and 100% during long-term follow-up of up to 8 years.

Patients experienced a rapid loss of inhibitor activity and recovery of FVIII levels, with median times of 3 days for inhibitor detection loss and 13 days for FVIII substitution, indicating the protocol's efficacy in managing life-threatening bleeding situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracorporeal Treatment for the Acute und Long-Term Outcome of Patients with Life-Threatening Acquired Hemophilia. Zeitler, H., Ulrich-Merzenich, G., Panek, D., et al.[2021]

A 5-year study involving 248 patients assessed the long-term safety of biological treatments, reporting that 17% experienced adverse events, primarily skin reactions (35%) and infections (28%).

The study found no unexpected adverse events in patients with rheumatoid arthritis and spondylarthropathy, suggesting that biological treatments are safe when managed by Finnish rheumatologists, even in combination with other common therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events. Konttinen, L., Honkanen, V., Uotila, T., et al.[2018]

Older patients (75+) using biological disease-modifying antirheumatic drugs (bDMARDs) experience a higher incidence of adverse events (AEs), particularly severe and infectious AEs, compared to younger age groups.

Despite the increased risk of AEs, the remission rate among patients aged 75 and older was significantly higher than in those aged 65-74, suggesting that bDMARDs may still be effective in this older population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) in Older Patients Treated for Rheumatoid Arthritis. Akter, R., Maksymowych, WP., Martin, ML., et al.[2023]

A pooled analysis of 1185 patients with relapsed/refractory multiple myeloma treated with bispecific antibodies (BsAbs) showed promising response rates, particularly with agents targeting B-cell maturation antigen (BCMA), although the median follow-up was short at 6.1 months.

Infectious complications were significant, with 50% of patients experiencing infections and 25.5% of deaths attributed to infections, highlighting the need for precautions to manage and treat infections in patients receiving BsAbs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis. Mazahreh, F., Mazahreh, L., Schinke, C., et al.[2023]

A survey of 290 haemophilia patients in Bavaria revealed that most patients are satisfied with their medical care and receive prophylactic therapy, with over 80% of patients under 25 and over 60% of those 25 and older receiving it regularly.

Chronic pain becomes a significant issue as patients age, and there is a strong interest across all age groups for more information on current scientific advancements, highlighting the need for additional psychosocial support alongside medical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wishes and worries of haemophilia patients. A patient survey from Bavaria. Lechner, H., Schleiermacher, A., Berger, K., et al.[2018]

BAX326 (RIXUBIS) is a newly approved recombinant factor IX concentrate that has shown efficacy and safety in treating hemophilia B, based on Phase III studies involving various treatment settings.

Prophylactic use of BAX326 significantly improves physical health-related quality of life for patients, indicating its potential to enhance overall outcomes for individuals with hemophilia B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BAX326 (recombinant coagulation factor IX) for the treatment and prophylaxis of hemophilia B. Windyga, J., Abbuehl, BE., Hafeman, AE.[2014]

A survey of 290 haemophilia patients in Bavaria revealed that the majority are satisfied with their medical care, with high rates of prophylactic therapy adherence among severe cases, indicating effective management of the condition.

Chronic pain becomes a significant issue as patients age, and there is a strong interest across all age groups for more information on current scientific advancements, highlighting a need for additional psychosocial support alongside medical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wishes and worries of haemophilia patients. Lechner, H., Schleiermacher, A., Berger, K., et al.[2020]

Patients with haemophilia B reported lower health-related quality of life (HRQoL) scores compared to the general US population, indicating a significant burden from the condition.

Prophylactic treatment with recombinant factor IX (BAX326) led to statistically significant improvements in physical HRQoL, particularly in areas like bodily pain and role physical functioning, especially for those who switched from on-demand treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in health-related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study. Windyga, J., Lin, VW., Epstein, JD., et al.[2015]

Citations

1. hematologyadvisor.com hematologyadvisor.com/news/hemophilia-first-patient-become9-trial-treatment-risk/

First Patient Dosed in BeCoMe-9 Trial of BE-101 for ... “BE-101 has the potential to be an important new therapeutic option in hemophilia B by delivering sustained FIX levels and durable bleed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06611436

NCT06611436 | BeCoMe-9: A Clinical Study of BE-101 for ... BE-101 is an autologous (person's own cells) B Cell Medicine (BCM) which uses CRISPR/Cas9 gene editing to precisely insert human FIX gene into those cells.

3. cell.com cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(25)00729-4

A precision gene-engineered B cell medicine producing ... In this paper, we describe pre-clinical studies characterizing an autologous ex vivo precision gene-edited cell therapy (termed BE-101) ...

4. be.bio be.bio/be-biopharma-announces-fda-clearance-of-ind-application-for-be-101-in-hemophilia-b/

Be Biopharma Announces FDA Clearance of IND ... BE-101 is the first engineered B Cell Medicine to Enter Clinical Trials for Hemophilia B Initiation of BeCoMe-9 Phase 1/2 Clinical Study Expected in the Second ...

5. bleeding.org bleeding.org/news/be-biopharma-announces-first-hemophilia-patient-dosed-with-new-cell-therapy

First Patient Treated in Hemophilia B Cell Therapy Trial The ongoing BeCoMe-9 Phase 1/2 study is evaluating the safety and efficacy of BE-101 in adults with moderately severe to severe hemophilia B.

6. be.bio be.bio/be-bio-announces-new-preclinical-data-demonstrating-its-novel-engineered-b-cell-medicine-bcm-be-101-produces-active-and-sustained-levels-of-factor-ix-for-the-treatment-of-hemophilia-b/

Be Bio Announces New Preclinical Data Demonstrating its ... The company's novel engineered BCM, BE-101, produces active and sustained levels of Factor IX (FIX) for the treatment of hemophilia B.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124083083

Become-9: A Phase 1/2 Dose Escalation and Expansion ... The BeCoMe-9 Study (Study BE-101-01) is a Phase 1/2, first in human, multi-center, open-label, dose-escalation study to evaluate the safety and ...