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NCT Number: NCT04819841

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

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.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

12 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Children's Hospital Los Angeles, Los Angeles, California, United States

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

nula-cel Drug Product

Genetic

nula-cel is administered via IV infusion following a myeloablative conditioning regimen

Primary outcomes

  1. Proportion of patients who reach neutrophil engraftment

    Time frame: 42 days post-infusion

  2. Incidence rate of treatment-related mortality

    Time frame: 100 days post-infusion

  3. Incidence rate of treatment-related mortality

    Time frame: 12 months post-infusion

  4. Overall survival

    Time frame: 24 months post-infusion

  5. Frequency and severity of AEs/SAEs

    Time frame: 24 months post-infusion

Secondary outcomes

  1. Time to neutrophil engraftment

    Time frame: through study completion, up to 24 months post-infusion

  2. Time to platelet engraftment

    Time frame: through study completion, up to 24 months post-infusion

  3. Evaluation of gene correction levels in peripheral myeloid cells

    Time frame: through study completion, up to 24 months post-infusion

  4. Evaluation of adult Hgb as a percentage of total Hgb

    Time frame: through study completion, up to 24 months post-infusion

  5. Evaluation of HbS as a percentage of total Hgb

    Time frame: through study completion, up to 24 months post-infusion

  6. Total Hgb without disease-indicated transfusion support

    Time frame: through study completion, up to 24 months post-infusion

  7. Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications

    Time frame: through study completion, up to 24 months post-infusion

  8. Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)

    Time frame: over time, from 6 months to 18 months post-infusion

  9. Incidence rate of any sVOCs

    Time frame: over time, from 6 months to study completion, up to 24 months post-infusion

  10. Proportion of participants achieving HbS <50% for at least 3 months

    Time frame: through study completion, up to 24 months post-infusion

  11. Evaluation of globin chain expression compared to baseline

    Time frame: through study completion, up to 24 months post-infusion

Study contacts

Contact information is provided by the study sponsor or research team.

Restore Clinical Study Support

CONTACT

[email protected]

650-442-2283

Sponsors and collaborators

Lead sponsor

Kamau Therapeutics

Industry

Registry information

Official study 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

Acronym: Restore

Important dates

Study start
2021
Primary completion
2026
Study completion
2028
First posted
Mar 29, 2021
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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