Transplantation of CRISPRCas9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients With Severe Sickle Cell Disease

Study point of contact

Christina Chun, MPH
(415) 502-2558
[email protected]
Mark Walters, MD
(510) 428-3374
[email protected]


2 United States sites


12 to 35 Years


Phase 1/Phase 2

Study type








About the study

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).

participation requirements

1. Male or female 12.00 – 34.99 years of age (at time of consent) who have one or more of
the following:

1. 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);

2. 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) 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 intravenous analgesics.

2. Participants must have adequate physical function as measured by all of the following:

1. Karnofsky performance score ≥60.

2. Cardiac function: Left ventricular ejection fraction (LVEF) >40%; or LV
shortening fraction > 26% by cardiac echocardiogram or by (multiple-gated
acquisition) MUGA scan.

3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥85% and
diffusion capacity of lung for carbon monoxide(DLCO) > 40% (corrected for

4. 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.

5. 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. f. Liver MRI using a validated methodology per institutional preference (T2* or R2* or by ferriscan [R2 MRI]) for estimation of hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions per year for ≥1 year or have received ≥20 packed red blood cell transfusions (lifetime cumulative). Participants who have hepatic iron content ≥ 8 mg Fe/g liver dry weight by liver MRI must have a Gastroenterology/hepatology consultation with liver biopsy and histological examination including documentation of the absence of cirrhosis, bridging fibrosis[1], and active hepatitis. 3. Written informed consent or assent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

participation restrictions

1. 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).

2. Participants with evidence of HIV infection or seropositivity for HIV or active
hepatitis B or C.

3. Participants who have received a Hematopoietic Cell Transplant (HCT)

4. Participants who have received a solid organ transplant.

5. 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.

6. Females who are pregnant or breast feeding.

7. 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.

8. 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.

9. Participants who have had a stroke OR who are receiving red blood cell (RBC)
transfusions to prevent primary stroke or silent cerebral infarction.

10. Patients who have a human leukocyte antigen identical (HLA-ID) sibling donor

11. 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.

12. Any non-homozygous sickle hemoglobin (HbSS) genotype of SCD


  • Los Angeles, California, United States, University of California, Los Angeles, 90095
  • Oakland, California, United States, UCSF Benioff Children's Hospital, 94609