Sickle Cell Disease
Conditions
Keywords
sickle cell disease, sickle cell anemia, gene correction, gene therapy, CRISPR
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.
Interventions
GENETICnula-cel Drug Product
nula-cel is administered via IV infusion following a myeloablative conditioning regimen
Sponsors
Kamau Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | 24 months post-infusion |
| Frequency and severity of AEs/SAEs | 24 months post-infusion |
| Proportion of patients who reach neutrophil engraftment | 42 days post-infusion |
| Incidence rate of treatment-related mortality | 100 days post-infusion |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Time to neutrophil engraftment | 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 platelet engraftment | 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 |
| Evaluation of globin chain expression compared to baseline | through study completion, up to 24 months post-infusion |
Countries
United States
Contacts
CONTACTRestore Clinical Study Support
STUDY_DIRECTORMatthew Porteus, MD, PhD
Kamau Therapeutics
Outcome results
None listed