Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease

Sickle Cell Disease Clinical Trial

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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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04819841
• Other study ID #: KMAU-001-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 15, 2021
• Est. completion date: July 31, 2027

Study information

• Verified date: January 2024
• Source: Kamau Therapeutics
• Contact: Jenni Herber
• Phone: 303-437-7356
• Email: jherber[@]kamautx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Participants diagnosed with severe SCD will receive nula-cel via IV infusion following myeloablative conditioning in an autologous HSCT setting.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: July 31, 2027
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Genetic:
• nula-cel Drug Product
nula-cel is administered via IV infusion following a myeloablative conditioning regimen

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Lucile Packard Children's Hospital	Palo Alto	California
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Kamau Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who reach neutrophil engraftment		42 days post-infusion
Primary	Incidence rate of treatment-related mortality		100 days post-infusion
Primary	Incidence rate of treatment-related mortality		12 months post-infusion
Primary	Overall survival		24 months post-infusion
Primary	Frequency and severity of AEs/SAEs		24 months post-infusion
Secondary	Time to neutrophil engraftment		through study completion, up to 24 months post-infusion
Secondary	Time to platelet engraftment		through study completion, up to 24 months post-infusion
Secondary	Evaluation of gene correction levels in peripheral myeloid cells		through study completion, up to 24 months post-infusion
Secondary	Evaluation of adult Hgb as a percentage of total Hgb		through study completion, up to 24 months post-infusion
Secondary	Evaluation of HbS as a percentage of total Hgb		through study completion, up to 24 months post-infusion
Secondary	Total Hgb without disease-indicated transfusion support		through study completion, up to 24 months post-infusion
Secondary	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
Secondary	Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)		over time, from 6 months to 18 months post-infusion
Secondary	Incidence rate of any sVOCs		over time, from 6 months to study completion, up to 24 months post-infusion
Secondary	Proportion of participants achieving HbS <50% for at least 3 months		through study completion, up to 24 months post-infusion
Secondary	Evaluation of globin chain expression compared to baseline		through study completion, up to 24 months post-infusion