Hemophilia B, Hemophilia B, Moderately Severe or Severe
Conditions
Keywords
Hemophilia B, Dose Escalation
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.
Interventions
DRUGBE-101
IV Infusion of BE-101 dose from Dose Level 1
Sponsors
Be Biopharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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 * Planned surgical procedure within 6 months from BE-101 administration * Previously dosed with gene therapy * Participated in an interventional study and/or received an interventional study drug within 30 days or five-half-lives (whichever is longer) of consent into BeCoMe-9 and for the duration of the study * Planned participation in clinical trial within one year after BE-101 * Administration of an investigational agent or vaccine within 28 days of leukapheresis and dosing of BE-101 Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) and Serious Adverse Events (SAEs) | 1 year post dose | Incidence of AEs and SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FIX Activity | Baseline to 1 year post dose | Change From Baseline in FIX Activity |
| Annualized Bleed Rate (ABR) | 1 year post dose | ABR (spontaneous and traumatic) for all bleeds. Annualized bleed rates overall and by severity will be presented. |
| Bleeding Episodes | 1 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 Joints | 1 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). |
| FIX Antigen Concentration | Baseline to 1 year post dose | Change From Baseline in FIX Antigen concentration |
| Exogenous FIX Concentrate | 1 year post dose | Number of infusions of exogenous FIX concentrate |
| FIX Replacement Therapy | 1 year post dose | Total consumption of exogenous FIX replacement therapy (IU) after BE-101 administration |
| FIX Inhibitor | 1 year post dose | FIX inhibitor development post BE-101 administration |
Countries
United States
Outcome results
None listed