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

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: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Genetic: nula-cel Drug Product

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Restore Clinical Study Support; Phone Number: 650-442-2283; Email: RestoreStudySupport@kamautx.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles
      • Contact: Joseph Abdelmessih; Phone Number: 323-361-7464; Email: jabdelmessih@chla.usc.edu
      • Principal Investigator: Ashley Gray, MD
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital
      • Sub-Investigator: David Shyr, MD
      • Contact: Stanford Intake Team; Email: scgt_clinical_trials_office@lists.stanford.edu
      • Contact: Kat Joseph, BSN, RN; Phone Number: 650-725-9032; Email: kjoseph3@stanford.edu
      • Principal Investigator: May Chien, MD
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Maggie Nash; Phone Number: 314-273-5936; Email: nashm@wustl.edu
      • Principal Investigator: John F Dipersio, MD, PhD
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Lauren Rayman; Email: lauren.rayman2@nationwidechildrens.org
      • Contact: Dalena Sanderson; Email: Dalena.Sanderson@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Time Frame
Proportion of patients who reach neutrophil engraftment	42 days post-infusion
Incidence rate of treatment-related mortality	100 days post-infusion
Incidence rate of treatment-related mortality	12 months post-infusion
Overall survival	24 months post-infusion
Frequency and severity of AEs/SAEs	24 months post-infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Kamau Therapeutics
• Investigators: Study Director: Mathew Porteus, MD, PhD, Kamau Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: gene therapy; sickle cell disease; sickle cell anemia; CRISPR; gene correction
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell
• Other Study ID 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