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

June 30, 2026 updated by: Kamau Therapeutics

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
        • Principal Investigator:
          • Ashley Gray, MD
        • Contact:
      • Palo Alto, California, United States, 94304
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Contact:
        • Principal Investigator:
          • John F Dipersio, MD, PhD
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Principal Investigator:
          • Monica Bhatia, MD
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marcus Mapara, MD
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering
        • Contact:
        • Principal Investigator:
          • Jaap Jan Boelens, MD, PhD
    • Ohio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: nula-cel Drug Product
nula-cel Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.
Genetic: nula-cel Drug Product
nula-cel is administered via IV infusion following a myeloablative conditioning regimen

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Proportion of patients who reach neutrophil engraftment
Time Frame: 42 days post-infusion
42 days post-infusion
Incidence rate of treatment-related mortality
Time Frame: 100 days post-infusion
100 days post-infusion
Incidence rate of treatment-related mortality
Time Frame: 12 months post-infusion
12 months post-infusion
Overall survival
Time Frame: 24 months post-infusion
24 months post-infusion
Frequency and severity of AEs/SAEs
Time Frame: 24 months post-infusion
24 months post-infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Time to neutrophil engraftment
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Time to platelet engraftment
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Evaluation of gene correction levels in peripheral myeloid cells
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Evaluation of adult Hgb as a percentage of total Hgb
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Evaluation of HbS as a percentage of total Hgb
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Total Hgb without disease-indicated transfusion support
Time Frame: through study completion, up to 24 months post-infusion
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
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)
Time Frame: over time, from 6 months to 18 months post-infusion
over time, from 6 months to 18 months post-infusion
Incidence rate of any sVOCs
Time Frame: over time, from 6 months to study completion, up to 24 months post-infusion
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
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion
Evaluation of globin chain expression compared to baseline
Time Frame: through study completion, up to 24 months post-infusion
through study completion, up to 24 months post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kamau Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Matthew Porteus, MD, PhD, Kamau Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 15, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 29, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KMAU-001-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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