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

Kamau Therapeutics6 sites in 1 country15 target enrollmentNovember 15, 2021

ConditionsSickle Cell Disease

Interventionsnula-cel Drug Product

Overview

Phase: Phase 1
Intervention: nula-cel Drug Product
Conditions: Sickle Cell Disease
Sponsor: Kamau Therapeutics
Enrollment: 15
Locations: 6
Primary Endpoint: Proportion of patients who reach neutrophil engraftment
Status: Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 15, 2021

End Date

December 31, 2028

Last Updated

last month

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Kamau Therapeutics

Responsible Party

Sponsor

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

Arms & Interventions

nula-cel Drug Product

nula-cel Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.

Intervention: nula-cel Drug Product

Outcomes

Primary Outcomes

Proportion of patients who reach neutrophil engraftment

Time Frame: 42 days post-infusion

Incidence rate of treatment-related mortality

Time Frame: 12 months post-infusion

Overall survival

Time Frame: 24 months post-infusion

Frequency and severity of AEs/SAEs

Time Frame: 24 months post-infusion

Incidence rate of treatment-related mortality

Time Frame: 100 days post-infusion

Secondary Outcomes

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)
Evaluation of globin chain expression compared to baseline(through study completion, up to 24 months post-infusion)