Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/ βC Genotype

NCT05951205 — Phase 3, Withdrawn, Vertex Pharmaceuticals Incorporated
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A Phase 3 Study to Evaluate Efficacy and Safety of a Single Dose of Exa-cel in Subjects With Severe Sickle Cell Disease, βS/βC Genotype

RegistryNCT05951205
StatusWithdrawn - Modification to the clinical development plan
PhasePhase 3
Study typeInterventional; na, single group, masking: none, treatment
SponsorVertex Pharmaceuticals Incorporated (Industry)
ConditionsSickle Cell Disease
InterventionsExa-cel (Biological)
Datesstart 2027-07-31 (estimated), primary completion 2033-12-31 (estimated), completion 2033-12-31 (estimated), first posted 2023-07-18, last updated 2026-03-25

Related Papers Related Patents Related Grants Related Experts
All trials for Sickle Cell Disease All trials of Exa-cel

-Summary

The purpose of the study is to evaluate the efficacy and safety of CTX001 (exa-cel) in adolescent and adult participants with severe sickle cell disease (SCD), βS/βC genotype (HbSC).

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+Arms and interventions

ArmTypeInterventionsDescription
Exa-celExperimentalBiological: Exa-celParticipants will receive a single infusion of exa-cel (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene) through a central venous catheter.
  • Exa-cel (Biological), also known as Exagamglogene autotemcel, CTX001: Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.

+Outcome measures

Primary outcomes

  • Proportion of Participants with an Average Fetal Hemoglobin (HbF) Greater Than or Equal To (>=) 20 percent (%) on or After 6 Months [From 60 Days after Last Red Blood Cell (RBC) transfusion up to 24 Months after exa-cel infusion]

Secondary outcomes

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From Signing of Informed Consent up to 24 Months After exa-cel Infusion]
  • Proportion of Participants With Neutrophil Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days) [Within 42 Days After exa-cel Infusion]
  • Time to Neutrophil Engraftment [Up to 24 months After exa-cel Infusion]
  • Time to Platelet Engraftment [Up to 24 months After exa-cel Infusion]
  • Incidence of Transplant-Related Mortality (TRM) [Up to 100 Days After exa-cel Infusion]
  • Incidence of Transplant-Related Mortality (TRM) [Within 12 Months After exa-cel Infusion]
  • Incidence of All-cause Mortality [From Signing of Informed Consent up to 24 Months After exa-cel Infusion]
  • Proportion of Participants With No Severe Vaso-Occlusive Crises (VOCs) for At least 12 Months (VF12) [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
  • Proportion of Participants Free from Inpatient Hospitalization For Severe VOCs Sustained for At least 12 Months (HF12) [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
  • Relative Reduction in Annualized Rate of Severe VOCs [From Baseline up to 24 Months After exa-cel Infusion]
  • Duration of Severe VOC Free in Participants who Have Achieved VF12 [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
  • Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs [From Baseline up to 24 Months After exa-cel Infusion]
  • Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs [From Baseline up to 24 Months After exa-cel Infusion]
  • Proportion of Participants With Sustained HbF >= 20 % for At least 3, 6, or 12 months [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
  • Relative Reduction in Annualized Volume of RBC Transfusions [From Baseline Up To 24 Months After exa-cel Infusion]
  • HbF Concentration Over Time [Up To 24 Months After exa-cel Infusion]
  • Total Hemoglobin (Hb) Concentration Over Time [Up To 24 Months After exa-cel Infusion]
  • Change In Reticulocyte Count Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Indirect Bilirubin Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Haptoglobin Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Lactate dehydrogenase (LDH) Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
  • Time to First Detectable Haptoglobin [Up to 24 Months After exa-cel Infusion]
  • Time to First Normalized LDH [Up to 24 Months After exa-cel Infusion]
  • Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [Up To 24 Months After exa-cel Infusion]
  • Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [Up To 24 Months After exa-cel Infusion]
  • Change in Pain Scale (11-point numerical rating scale (NRS)) Assessment Over Time In Adults (>=18 Years) [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Over Time In Adults (>=18 Years) [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Pain Scale (11-point NRS) Assessment Over Time In Adolescents (12 to <18 years of age) [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in Pediatric Quality of Life Inventory (PedsQL; self-report and parent proxy versions) Generic Core In Adolescents (12 to <18 years of age) [From Baseline Up To 24 Months After exa-cel Infusion]
  • Change in PedsQL SCD module (self-report and parent proxy versions) In Adolescents (12 to <18 years of age) [From Baseline Up To 24 Months After exa-cel Infusion]

+Eligibility

Sex: All, ages: 12 Years to 35 Years

Key Inclusion Criteria:

* Participants with documented βS/βC (HbSC) genotype
* Participants must be eligible for autologous stem cell transplant as per investigator's judgment

Key Exclusion Criteria:

* A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
* Participants with prior hematopoietic stem cell transplant (HSCT)
* Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.

Other protocol defined Inclusion/Exclusion criteria may apply.

+Funding

NIH grants: 2023