Transplantation of Clustered Regularly Interspaced Short Palindromic Repeats Modified Hematopoietic Progenitor Stem Cells (CRISPR_SCD001) in Patients With Severe Sickle Cell Disease

NCT04774536 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-33287
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, non-randomized, 2-center, phase 1/2 trial of a single infusion of sickle allele modified cluster of differentiation (CD34+) hematopoietic stem progenitor cells (HSPCs) in subjects with in subjects ≥12 years old to 35 years old severe Sickle Cell Disease (SCD). The study will evaluate the hematopoietic stem cell transplantation (HSCT) using CRISPR/Cas9 edited red blood cells (known as CRISPR\_SCD001 Drug Product).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events and grade 3 or higher serious adverse events, using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE)

  The adverse event rate will be summarized using descriptive statistics, together with 95% confidence intervals where appropriate. No formal statistical hypothesis testing will be performed. Adverse events defined: failure of engraftment, malignant clonal expansion related to genomic editing or death.

  24 months post-transplant

Secondary Outcomes (12)

• Change in the annualized vaso-occlusive pain event (VOE) rates.

  24 months pre-transplant to 24 months post-transplant

• Graft rejection defined as having an absolute neutrophil count (ANC) < 500 at 42 days post-infusion

  42 days post-transplant

• Time to neutrophil recovery defined as the first of 3 measurements on different days when the patient has an absolute neutrophil count (ANC) of ≥500/µL after transplant.

  24 months post-transplant

• Time to platelet recovery is defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count > 50,000/µL AND did not receive a platelet transfusion in the previous 7 days.

  baseline, through 24 months post-transplant

• Rate of improvement in Hemoglobin S (HbS) fraction as measured by hemoglobin electrophoresis, as percent of total.

  baseline, through 24 months post-transplant

Other Outcomes (6)

• Rate of sickle-related events other than severe VOE and end organ function.

  24 months post-infusion

• Patient-reported quality of life (pain and fatigue domains) as measured by the use of Patient Reported Outcome Measurement Information System (PROMIS) modules.

  baseline, and 1 and 2 years post-transplant

• Change from baseline in cardiac-pulmonary function via pulmonary function tests

  Through 1 and 2 years post-transplant

Study Arms (1)

CRISPR_SCD001 Drug Product

EXPERIMENTAL

CRISPR\_SCD001 Drug Product (autologous CD34+ cell-enriched population that contains cells modified by the CRISPR-Cas9 ribonucleoprotein) dose will be ≥3.0×106 CD34+ cells/kg recipient weight for each subject and the upper limit cell dose is 20 ×106 CD34+ cells/kg.

Drug: CRISPR_SCD001

Interventions

CRISPR_SCD001 DRUG

CRISPR\_SCD001 is administered by IV infusion following myeloablative conditioning with busulfan.

CRISPR_SCD001 Drug Product

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female 12.00 - 34.99 years of age (at time of consent) who have one or more of the following:
• History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea); ACS is defined as a new radiodensity on chest imaging accompanied by fever and/or respiratory symptoms, treated in the hospital with supplemental oxygen at a minimum.
• History of at least 4 severe vaso-occlusive pain events in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes related to or any sickle-related acute event are acceptable; a severe painful vaso-occlusive event is defined as receiving analgesic treatment (opioid or other analgesic via parenteral (PN) route) for longer than 24 -hours in a hospital or emergency room (ER) observation unit visit or at least 2 visits in a day unit or ER over 72 hours with both visits requiring parenteral analgesics.
• or more episodes of splenic sequestration, defined as an acute decrease in hemoglobin by at least 2 g/dL accompanied by splenomegaly in the 2 years before enrollment.
• Recurrent priapism (episodes lasting at least 4 hours at least twice in the last 12 months or 3 times in the last 24 months before enrollment) recalcitrant to medical treatment
• Any episode of hepatic sequestration defined as right upper quadrant pain, hepatomegaly, and rapidly decreasing hemoglobin level with hepatic dysfunction within the 2 years before enrollment.
• Leg ulcer recalcitrant to treatment within 2 years prior to enrollment.
• Participants must have adequate physical function as measured by all of the following:
• Karnofsky performance score ≥60.
• Cardiac function: Left ventricular ejection fraction (LVEF) \>40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by (multiple-gated acquisition) MUGA scan.
• Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥85% and diffusion capacity of lung for carbon monoxide(DLCO) \> 40% (corrected for hemoglobin).
• Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated or measured creatinine clearance ≥ 70 mL/min/1.73 m2.
• Hepatic function:
• i. Serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory. Participants with hyperbilirubinemia as the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded.
• ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AS \< 5 times upper limit of normal as per local laboratory.

You may not qualify if:

• Participants with uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
• Participants with evidence of HIV infection or seropositivity for HIV or active hepatitis B or C.
• Participants who have received a Hematopoietic Cell Transplant (HCT)
• Participants who have received a solid organ transplant.
• Participants who have participated in another clinical trial in which the participant received an investigational or off-label use of a drug or device within 3 months prior to enrollment.
• Females who are pregnant or breast feeding.
• Females of child bearing potential (to include all female participants \> 10 years of age, unless postmenopausal for a minimum of 1 year before the time of consent or surgically sterilized) who do not agree to practice two (2) effective methods of contraception at the same time, or who do not agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject, from the time of signing of informed consent through 12 months post-stem cell infusion.
• Males (even if surgically sterilized) who do not agree to practice effective barrier contraception, or who do not agree to practice true abstinence from the time of signing informed consent through 12 months post-stem cell infusion.
• Participants who have had a stroke OR who are receiving red blood cell (RBC) transfusions to prevent primary stroke or silent cerebral infarction.
• Patients who have a suitable human leukocyte antigen identical (HLA-ID) sibling donor willing and able to donate bone marrow.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Any non-homozygous sickle hemoglobin (HbSS) genotype of SCD
• Either or both of the following findings on screening bone marrow aspirate/biopsy:
• diagnosis of myelodysplastic syndrome (MDS) based on morphology and/or cytogenetics (based on WHO definitions) OR
• any evidence of a pathogenic clonal variant in any candidate gene detected by a standard, licensed next-generation sequencing clinical assay for gene mutations associated with hematological malignancies.

Sponsors & Collaborators

• Mark Walters, MD: lead
• University of California, Los Angeles: collaborator
• University of California, Berkeley: collaborator

Study Sites (2)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

UCSF Benioff Children&#39;s Hospital

Oakland, California, 94609, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Mark Walters, MD

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Walters, MD

CONTACT

(510) 428-3374; Mark.Walters@ucsf.edu

Christina Chun, MPH

CONTACT

(415) 502-2558; Christina.Chun@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor in Residence

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: March 1, 2021
• Study Start: August 22, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)