NCT05456880
Active, Not Recruiting
Phase 1
A Phase 1/2 Study Evaluating the Safety and Efficacy of a Single Dose of Autologous CD34+ Base Edited Hematopoietic Stem Cells (BEAM-101) in Patients With Sickle Cell Disease and Severe Vaso-Occlusive Crises (Beacon Trial)
Overview
- Phase
- Phase 1
- Intervention
- BEAM-101
- Conditions
- Sickle Cell Disease
- Sponsor
- Beam Therapeutics Inc.
- Enrollment
- 15
- Locations
- 19
- Primary Endpoint
- Proportion of patients with successful neutrophil engraftment
- Status
- Active, Not Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is an open-label, single-arm, multicenter, Phase 1/2 study evaluating the safety and efficacy of the administration of autologous base edited CD34+ HSPCs (BEAM-101) in patients with severe SCD
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
BEAM-101
BEAM-101 manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and edited ex vivo. No maximum dose has been set for BEAM-101; all of the gene edited cells that pass release specifications will be administered to the patient. BEAM 101 will be administered as a single dose by IV infusion.
Intervention: BEAM-101
Outcomes
Primary Outcomes
Proportion of patients with successful neutrophil engraftment
Time Frame: BEAM-101 administration to month 24
Time to neutrophil engraftment
Time Frame: BEAM-101 administration to month 24
Safety and tolerability assessments based on frequency, severity and seriousness of adverse events (AE's)
Time Frame: BEAM-101 administration through month 24
Time to platelet engraftment
Time Frame: BEAM-101 administration to month 24
Transplant-related mortality within 100 days after beam-101 treatment
Time Frame: BEAM-101 administration to day 100
Change in annualized number of severe VOCs (Vascular-occlusive Crisis) relative to baseline
Time Frame: 6 months to time of analysis as compared to baseline
Secondary Outcomes
- Change in free Hgb over time(Month 3 post BEAM-101 treatment to month 24 as compared to baseline)
- Change in annualized duration of hospitalizations for VOCs(Month 6 post BEAM-101 treatment to month 24 as compared to baseline)
- Proportion of patients with HbF ≥30%, for at least 3 months(Month 6 post BEAM-101 treatment to month 24 as compared to baseline)
- Change in total bilirubin over time(Month 3 post BEAM-101 treatment to month 24 as compared to baseline)
- Proportion of patients experiencing at least 75% reduction in annualized rate of severe VOCs(Month 6 post BEAM-101 treatment to month 24 as compared to baseline)
- Proportion of patients experiencing no severe VOCs(6 months to time of analysis as compared to baseline)
- Change in lactate dehydrogenase (LDH) over time(Month 3 post BEAM-101 treatment to month 24 as compared to baseline)
- Change in reticulocyte count over time(Month 3 post BEAM-101 treatment to month 24 as compared to baseline)
- Change in total Hgb (g/dL) concentration over time(Baseline to month 24)
- Change in annualized number of hospitalizations for VOCs(Month 6 post BEAM-101 treatment to month 24 as compared to baseline)
- Change in RBC transfusions per month and per year for SCD-related indications(Month 2 post BEAM-101 treatment to month 24 as compared to baseline)
- Change in haptoglobin over time(Month 3 post BEAM-101 treatment to month 24 as compared to baseline)
Study Sites (19)
Loading locations...
Similar Trials
Active, Not Recruiting
Phase 2
PM8002 in Combination With Chemotherapy as First Line Therapy in Hepatocellular CarcinomaHepatocellular CarcinomaNCT05864105Biotheus Inc.35
Completed
Phase 2
KN046 in Subjects With Late Stage Esophageal Squamous Cell CarcinomaEsophageal Squamous Cell CarcinomaNCT03925870Jiangsu Alphamab Biopharmaceuticals Co., Ltd45
Withdrawn
Phase 2
A Study of Mitoxantrone Hydrochloride Liposome Injection for Relapsing Multiple SclerosisRelapsing Multiple SclerosisNCT05496894CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
Not Yet Recruiting
Phase 2
A Phase II Clinical Study to Evaluate the Safety, Pharmacokinetic Profile, and Preliminary Efficacy of IMM2510 in Combination with Chemotherapy As First-line Treatment in Subjects with Non-small Cell Lung Cancer or Triple-negative Breast CancerNSCLCTNBCNCT06746870ImmuneOnco Biopharmaceuticals (Shanghai) Inc.148
Active, Not Recruiting
Phase 2
A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating MutationsAdvanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,BreastNCT04639219AstraZeneca102
Related News
FDA Approves Autolus' Obecabtagene Autoleucel (Aucatzyl) for R/R B-cell ALL• The FDA has approved obecabtagene autoleucel (obe-cel), a CD19-directed CAR-T therapy, for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-cell ALL).
• Approval was based on the Phase 1b/2 FELIX trial, which demonstrated overall complete remission rates above 60% and durable remissions exceeding 12 months.
• Clinical holds on CARsgen's BCMA-directed CAR-T therapy zevorcabtagene autoleucel and Claudin18.2-directed CAR-T satricabtagene autoleucel have been removed by the FDA.Sickle Cell Disease Patient Death in Beam Therapeutics' BEACON Trial Highlights Conditioning Regimen Risks• A patient with sickle cell disease died from respiratory failure four months after receiving BEAM-101 in Beam Therapeutics' BEACON trial.
• The death was attributed to the busulfan-conditioning regimen, a known risk in myeloablative transplants, rather than the BEAM-101 therapy itself.
• Beam Therapeutics is developing an alternative approach, ESCAPE, using a CD117 monoclonal antibody to avoid the need for busulfan conditioning.
• Preclinical data in non-human primates showed that ESCAPE was well-tolerated and resulted in approximately 85% of red blood cells expressing HbF.Patient Death in Beam Therapeutics' Sickle Cell Trial Linked to Conditioning Regimen• A patient in Beam Therapeutics' BEACON trial of BEAM-101, a base editing therapy for sickle cell disease (SCD), died four months post-infusion due to respiratory failure.
• Investigators determined the death was likely related to the busulfan conditioning regimen and not directly caused by BEAM-101, according to Beam Therapeutics.
• The FDA and the BEACON trial's Data Safety Monitoring Committee reviewed the death, allowing the trial to proceed without protocol changes.
• The event underscores the need for less toxic preconditioning options in cell and gene therapy, as current regimens are associated with significant toxic effects.