A study to learn about the safety and efficacy of CTX001 (the study drug product) to treat Severe Sickle Cell Disease
- Conditions
- Severe Sickle Cell Disease (SCD)MedDRA version: 21.0Level: PTClassification code 10040641Term: Sickle cell anaemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2018-001320-19-DE
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 45
1. Subject, or their legally authorized representative or guardian, will sign and date an informed consent form (ICF) and, where applicable, an assent form.
2. Subjects 12 to 35 years of age, inclusive on the date of informed consent.
3. Documented ßS/ßS, ßS/ß0, or ßS/ß+ genotype. Subjects can be enrolled based on historical genotype results, but confirmation of genotype is required before busulfan conditioning. ß0 genotypes are defined using the HbVar Database.
4. Subjects with severe SCD. Severe SCD is defined by the occurrence of at least 2 of the following events per year during the 2-year period before screening, while receiving appropriate supportive care (e.g. pain management plan, hydroxyurea [HU]):
• Acute pain events that requires a visit to a medical facility and administration of pain medications (opioids or intravenous [IV] nonsteroidal anti-inflammatory drugs [NSAIDs]) or red blood cell (RBC) transfusions
• Acute chest syndrome, as indicated by the presence of a new pulmonary infiltrate associated with by pneumonia-like symptoms, pain, or fever
• Priapism lasting >2 hours and requiring a visit to a medical facility
• Splenic sequestration, as defined by an enlarged spleen, left upper quadrant pain, and an acute decrease in hemoglobin concentration of =2 g/dL.
Historical severe VOCs will be adjudicated by the Endpoint Adjudication Committee (EAC).
5. Normal transcranial Doppler (TCD) velocity (time-averaged mean of the maximum velocity [TAMMV] <170 cm/sec for non-imaging TCD and <155 cm/sec for imaging TCD) in the middle cerebral artery (MCA) and the internal carotid artery (ICA) for subjects 12 to 16 years of age.
6. Karnofsky performance status of =80% for subjects =16 years of age or Lansky performance status of =80% for subjects <16 years of age.
7. Eligible for autologous stem cell transplant as per investigator's judgment.
8. Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least 1 ovary, and is less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from consent through at least 6 months after CTX001 infusion.
9. Male subjects of reproductive capacity must agree to use effective contraception from start of mobilization through at least 6 months after CTX001 infusion
10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.
11. Willing to participate in the long-term follow-up study after (Study VX18-CTX001-131) after completion of this study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. An available 10/10 human leukocyte antigen (HLA)-matched related donor.
2. Prior Hematopoietic Stem Cell Transplant (HSCT).
3. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
4. White blood cell (WBC) count <3 × 109/L or platelet count <50 × 109/L, not related to hypersplenism per investigator judgment.
5. Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.
6. Subjects with history of alloimmunization to RBC antigens and for whom the investigator anticipates that there will be insufficient RBC units available for the duration of the study.
7. More than 10 unplanned hospitalizations or emergency department visits related to SCD in the 1 year before screening, that in the opinion of the investigator, are consistent with significant chronic pain rather than acute pain crises.
8. HbF level >15.0%, irrespective of concomitant treatment with fetal hemoglobin (HbF) inducing treatments such as HU.
9. History of abnormal TCD (TAMMV =200 cm/sec for non-imaging TCD and =185 cm/sec for imaging TCD) for subjects 12 to 18 years of age.
10. History of untreated Moyamoya disease or presence of Moyamoya disease at Screening that in the opinion of the investigator puts the subjects at the risk of bleeding.
11. History of a significant bleeding disorder.
12. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject. This may include, but is not limited to: history of relevant drug allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; history of mental disease; or history of familial cancer syndrome.
13. Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder.
14. Advanced liver disease, defined as
a. Alanine transaminase (ALT) >3 × the upper limit of normal (ULN) or direct bilirubin value >2.5 × ULN, or
b. Baseline prothrombin time (PT) (international normalized ratio [INR]) >1.5 × ULN, or
c. History of cirrhosis or any evidence of bridging fibrosis, or active hepatitis on liver biopsy
15. Baseline estimated glomerular filtration rate <60 mL/min/1.73 m2.
16. Lung diffusing capacity for carbon monoxide (DLco) <50% of predicted value (corrected for hemoglobin and/or alveolar volume).
17. Left ventricular ejection fraction (LVEF) <45% by echocardiogram.
18. Prior treatment with gene therapy/editing product.
19. Intolerance, contraindication, or known sensitivity to plerixafor or busulfan. Subject must not have any risk factors in the opinion of the investigator that would increase the likelihood of busulfan-related toxicities. Prior anaphylactic reaction with excipients of CTX001 product (dimethylsulfoxide [DMSO], dextran).
20. Positive for the presence of human immunodeficiency virus-1 (HIV-1) or human immunodeficiency virus-2 (HIV-2) (positive for both antigen/antibody AND nucleic acid tests [NAT]), hepatitis B virus (HBV) (positive for Hepatitis B core antibody [HBcAb] or
positive hepatitis B surface antigen [HBsAg] AND NAT tests), syphilis (positive screening AND positive confirmatory tests), or hepatitis C virus (HCV); positive for both antibody [HCAb] AND for NAT tests). Additional infectious disease markers should be obtained and tested as required by the local authority f
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method