Study conducted to learn more about the safety and effects of CTX001 (the Study Therapy”) in patients with Severe Sickle Cell Disease

Phase 1

• Conditions: Sickle Cell Disease; MedDRA version: 20.0Level: PTClassification code 10043391Term: Thalassaemia betaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2018-001320-19-IT
• Lead Sponsor: VERTEX PHARMACEUTICALS INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-25
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Subject will sign and date an informed consent form (ICF).
2. Subjects 18 to 35 years of age, inclusive on the date of informed consent.
3. Documented ßS/ßS genotype or ßS/ß0. Subjects can be enrolled based on historical genotype results, but confirmation of genotype is required before busulfan conditioning.The ß0 genotypes are defined
using the HbVar Database.
Protocol CTX001-121, Version 2.0 Page 35 of 82
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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, HU) as judged by the investigator:
• Acute pain events that requires a visit to a medical facility and administration of pain medications (opioids or intravenous [IV] non-steroidal anti-inflammatory drugs [NSAIDs]) or 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. Karnofsky performance status of =80%.
6. Eligible for autologous stem cell transplant as per investigator’s judgment.
7. 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.
8. Male subjects must agree to use effective contraception from start of mobilization through at least 6 months after CTX001 infusion
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.
10. Willing to participate in an additional long-term follow-up study (Study VX18-CTX001-131) after completion of this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. An available 10/10 human leukocyte antigen (HLA)-matched related donor.
2. Prior 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 HbF inducing treatments such as HU.
9. 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.
10. History of a significant bleeding disorder.
11. 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.
12. Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder.
13. Advanced liver disease, defined as
a. Alanine transaminase (ALT) >3 × the upper limit of normal (ULN) or direct bilirubin value >2 × 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
14. Baseline estimated glomerular filtration rate <60 mL/min/1.73 m2.
15. Lung diffusing capacity for carbon monoxide (DLco) <50% of predicted value (corrected for hemoglobin and/or alveolar volume).
16. Left ventricular ejection fraction (LVEF) <45% by echocardiogram.
17. Prior treatment with gene therapy/editing product.
18. Intolerance, contraindication, or known sensitivity to plerixafor or busulfan. Prior anaphylactic reaction with excipients of CTX001 product (dimethylsulfoxide [DMSO], dextran).
19. Positive for the presence of human immunodeficiency virus-1 (HIV1) or human immunodeficiency virus-2 (HIV-2) (positive
antigen/antibody AND nucleic acid tests [NAT]), hepatitis B virus (HBV)(positive Hepatitis B core antibody [HBcAb] AND NAT tests), syphilis (positive screening AND confirmatory tests), or hepatitis C virus (HCV; positive antibody [HCAb] AND NAT tests). Additional infectious disease markers should be obtained and tested as required by the local authority for the collection and processing of cellular therapy products. These additional tests (e.g., HTLV-1, HTLV-2, malaria, tuberculosis, toxoplasmosis,
Trypanosoma cruzi, or West e virus) will be evaluated to determine overall impact to the subject and manufacturing of CTX001.
20. Participation in another clinical study with an investigational drug/product within 30 days of screening or fewer than 5 half-lives of the inv

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified