Clinical trial NCT04819841: Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease
Official title: A Phase I/II Study of Nula-cel in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
sickle cell anemia
gene correction
gene therapy
CRISPR
Lead sponsor: Kamau Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-03-29
Enrollment: 15
Sex: ALL
Minimum age (years): 12
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients who reach neutrophil engraftment
timeFrame: 42 days post-infusion
measure: Incidence rate of treatment-related mortality
timeFrame: 100 days post-infusion
measure: Incidence rate of treatment-related mortality
timeFrame: 12 months post-infusion
measure: Overall survival
timeFrame: 24 months post-infusion
measure: Frequency and severity of AEs/SAEs
timeFrame: 24 months post-infusion
Secondary outcomes:
measure: Time to neutrophil engraftment
timeFrame: through study completion, up to 24 months post-infusion
measure: Time to platelet engraftment
timeFrame: through study completion, up to 24 months post-infusion
measure: Evaluation of gene correction levels in peripheral myeloid cells
timeFrame: through study completion, up to 24 months post-infusion
measure: Evaluation of adult Hgb as a percentage of total Hgb
timeFrame: through study completion, up to 24 months post-infusion
measure: Evaluation of HbS as a percentage of total Hgb
timeFrame: through study completion, up to 24 months post-infusion
measure: Total Hgb without disease-indicated transfusion support
timeFrame: through study completion, up to 24 months post-infusion
measure: Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications
timeFrame: through study completion, up to 24 months post-infusion
measure: Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)
timeFrame: over time, from 6 months to 18 months post-infusion
measure: Incidence rate of any sVOCs
timeFrame: over time, from 6 months to study completion, up to 24 months post-infusion
measure: Proportion of participants achieving HbS <50% for at least 3 months
timeFrame: through study completion, up to 24 months post-infusion
measure: Evaluation of globin chain expression compared to baseline
timeFrame: through study completion, up to 24 months post-infusion
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Kamau Therapeutics
name: Mathew Porteus, MD, PhD
role: STUDY_DIRECTOR
References: