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BeCoMe-9: a Clinical Study of BE-101 for the Treatment of Adults with Moderately Severe or Severe Hemophilia B

Phase 1
Recruiting
Conditions
Hemophilia B, Severe
Hemophilia B
Interventions
Registration Number
NCT06611436
Lead Sponsor
Be Biopharma
Brief Summary

The BeCoMe-9 Study (BE-101-01) is a Phase 1/2, first in human, multi-center, open-label, dose-escalation study to evaluate the safety and clinical activity of a single intravenous (IV) dose of BE-101 in adults with moderately severe or severe Hemophilia B. Once infused, BE-101 is designed to engraft and continuously secrete FIX into the circulation to restore clinically meaningful levels of active FIX. 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.

Detailed Description

The study includes 2 distinct parts: Part 1 and Part 2. In Part 1, an ascending-dose design will be utilized to enable evaluation of increasing doses in a stepwise manner. The objective for this dose escalation is to identify the dose of BE-101 required to achieve desired FIX activity 28 days after infusion. Upon identification of a safe and efficacious dose in Part 1, an expansion phase (Part 2) will initiate. The initial cohort in the Part 2 expansion (Part 2a) phase will include up to 6 adult participants to further characterize the safety and activity of BE-101 at the selected dose. Additional cohorts for adolescents and redosing for participants in Part 1 of the study will occur following data availability of Part 1.

Up to 24 participants will be enrolled across Part 1 (up to 18) and Part 2a (up to 6). Consented participants will complete a screening period to assess eligibility and upon enrollment will undergo leukapheresis collection to support BE-101 manufacturing. Following administration, participants will be monitored for safety and clinical activity. The total duration of study participation is approximately 52 weeks post IV administration of BE-101.

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
24
Inclusion Criteria
  • Adult Males (≥18) with moderately severe to severe Hemophilia B (FIX deficiency)
  • Received ≥50 exposure days to Factor IX products preceding enrollment.
  • Currently receiving prophylaxis treatment
  • Adequate organ function and clinical labs
  • Able to tolerate study procedures including leukapheresis.
Exclusion Criteria
  • Pre-existing or history of specific diseases

    • B-Cell malignancy, EBV lymphoproliferative disease
    • Primary immunodeficiency disease or disorder (PIDD) or systemic immuno-suppression
    • Arterial and/or venous thromboembolic events within 2 years prior to dosing
    • History of anaphylaxis or nephrotic syndrome
    • Active infection (HIV, Hep B or C)
  • History of inhibitor to FIX or inhibitor

  • History of an allergic reaction or anaphylaxis to FIX products

  • Within 6 months from BE-101 administration:

    • Planned surgical procedure
    • Previously dosed with gene therapy or participated in an interventional clinical study
  • Planned participation in clinical trial within one year after BE-101

  • Administration of a vaccine within 28 days of dosing

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 1 - Dose Escalation, Dose Level 1BE-101-
Part 1 - Dose Escalation, Dose Level 2BE-101-
Part 1 - Dose Escalation, Dose Level 3BE-101-
Part 2 - Dose Expansion, Cohort 2a Adult Expansion, Optimal Dose Selected in Part 1 Dose EscalationBE-101-
Primary Outcome Measures
NameTimeMethod
Adverse events (AEs) and Serious Adverse Events (SAEs)1 year post dose

Incidence of AEs and SAEs

Secondary Outcome Measures
NameTimeMethod
FIX ActivityBaseline to 1 year post dose

Change From Baseline in FIX Activity

Annualized Bleeding Rate (ABR)1 year post dose

ABR (spontaneous and traumatic) for all bleeds. Annualized bleeding rates overall and by severity will be presented.

Bleeding Episodes1 year post dose

Number of bleeding episodes (total, spontaneous, and traumatic). Bleeding episodes will be summarized by subject and overall, and will include number, duration, and severity.

Target Joints1 year post dose

Number of target joints. A target joint is defined as a major joint (e.g. hip, elbow, wrist, shoulder, knee, ankle) into which repeated bleeding occurs (frequency of 3 or more bleeding episodes into the same joint in a consecutive 12 week period) and with symptoms of pre-existing target joint involvement (eg, synovitis, persistent swelling, effusion, limitation of range of motion).

Exogenous FIX Concentrate1 year post dose

Number of infusions of exogenous FIX concentrate

FIX Replacement Therapy1 year post dose

Total consumption of exogenous FIX replacement therapy (IU) after BE-101 administration

FIX Inhibitor1 year post dose

FIX inhibitor development post BE-101 administration

Trial Locations

Locations (3)

Washington Center for Bleeding Disorders

🇺🇸

Seattle, Washington, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

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