Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease
Phase 1
Recruiting
- Conditions
- Sickle Cell Disease
- Interventions
- Genetic: nula-cel Drug Product
- Registration Number
- NCT04819841
- Lead Sponsor
- Kamau Therapeutics
- Brief Summary
This study is a first-in-human, single-arm, open-label Phase I/II study of nula-cel in approximately 15 participants, diagnosed with severe Sickle Cell Disease. The primary objective is to evaluate safety of the treatment in this patient population, as well as preliminary efficacy and pharmacodynamic data.
- Detailed Description
Participants diagnosed with severe SCD will receive nula-cel via IV infusion following myeloablative conditioning in an autologous HSCT setting.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
Inclusion Criteria
- ≥12 to ≤ 40 years
- Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:
- recurrent severe VOC (≥ 4 episodes in the preceding 2 years)
- ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)
- Lansky/Karnofsky performance status of ≥ 80
Exclusion Criteria
- Available 10/10 HLA-matched sibling donor
- Prior HSCT or gene therapy
- Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder
- Clinically significant and active bacterial, viral, fungal or parasitic infection
- Pregnancy or breastfeeding in a postpartum female
- Presence of a chromosomal abnormality/mutation that may put the participant at an increased risk for MDS or AML per investigator's judgment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description nula-cel Drug Product nula-cel Drug Product nula-cel Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.
- Primary Outcome Measures
Name Time Method Proportion of patients who reach neutrophil engraftment 42 days post-infusion Incidence rate of treatment-related mortality 12 months post-infusion Overall survival 24 months post-infusion Frequency and severity of AEs/SAEs 24 months post-infusion
- Secondary Outcome Measures
Name Time Method Evaluation of globin chain expression compared to baseline through study completion, up to 24 months post-infusion Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications through study completion, up to 24 months post-infusion Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs) over time, from 6 months to 18 months post-infusion Time to neutrophil engraftment through study completion, up to 24 months post-infusion Time to platelet engraftment through study completion, up to 24 months post-infusion Evaluation of gene correction levels in peripheral myeloid cells through study completion, up to 24 months post-infusion Evaluation of adult Hgb as a percentage of total Hgb through study completion, up to 24 months post-infusion Evaluation of HbS as a percentage of total Hgb through study completion, up to 24 months post-infusion Total Hgb without disease-indicated transfusion support through study completion, up to 24 months post-infusion Incidence rate of any sVOCs over time, from 6 months to study completion, up to 24 months post-infusion Proportion of participants achieving HbS <50% for at least 3 months through study completion, up to 24 months post-infusion
Trial Locations
- Locations (3)
Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States