A study to learn about the safety and efficacy of CTX001 (the study drug product) to treat beta-thalassemia

Phase 1

Conditions: Transfusion-Dependent ß Thalassemia
MedDRA version: 20.0Level: PTClassification code 10043391Term: Thalassaemia betaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2017-003351-38-GB

Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 45

Inclusion Criteria

1. Subjects 12 to 35 years of age, inclusive on the date of informed consent
2. Subject (or their legally authorized representative or guardian) will sign and date an informed consent form (ICF) and, where applicable, an assent form
3. Diagnosis of transfusion-dependent ß-thalassemia (TDT) as defined by:
a. Documented homozygous ß-thalassemia or compound heterozygous ß-thalassemia including ß-thalassemia/hemoglobin E (HbE). Subjects can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning. The ß^0 and non ß^0 genotypes are defined using the HbVar Database.
b. A history of at least 100 mL/kg/year or 10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last
rescreening for patients going through repeat screening.
4. Karnofsky performance status of =80% for subjects =16 years of age. Lansky performance status of =80% for subjects <16 years of age.
5. Eligible for autologous stem cell transplant as per investigator’s judgment.
6. Access to detailed medical records on packed RBC transfusions, including volume or units of packed RBCs and associated pre-transfusion Hb values, and in-patient hospitalizations, for at least the 2 years prior to consent.
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 of reproductive capacity 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? 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

Exclusion Criteria

1. An available 10/10 Human Leukocyte Antigen (HLA)-matched related donor.
2. Prior allo-hematopoietic stem cell transplant (HSCT).
3. Subjects with associated a-thalassemia and >1 alpha chain deletion. or alpha multiplications.
4. Subjects with sickle cell beta thalassemia variant.
5. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
6. White blood cell (WBC) count <3 × 10^9/L or platelet count <50 × 10^9/L not related to hypersplenism per investigator judgement.
7. History of a significant bleeding disorder.
8. 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 in administering study drug to the subject. This may include, but is not limited to: immediate family member with a known family cancer syndrome, history of relevant drug allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; history of uncontrolled seizure disorders, or history of psychiatric disorders.
9. Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder.
10. Advanced liver disease, defined as:
a. Aspartate transaminase (AST), alanine transaminase (ALT) >3 x the upper limit of normal (ULN), or direct bilirubin value >2.5 x the ULN, or:
b. Baseline prothrombin time (International Normalized Ratio; INR) >1.5 x ULN, or
c. History of cirrhosis or any evidence of bridging fibrosis, or active hepatitis on previous liver biopsy.
d. Liver iron content (LIC) =15 mg/g on R2* MRI of liver.
11. A cardiac T2* <10 ms by MRI or left ventricular ejection fraction (LVEF) <45% by echocardiogram.
12. Baseline estimated glomerular filtration rate <60 mL/min/1.73 m^2.
13. Diffusing capacity of the lungs for carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin and/or alveolar volume).
14. Prior treatment with gene therapy/editing product.
15. Intolerance, contraindication, or known sensitivity to plerixafor, granulocyte colony stimulating factor (G-CSF) products (e.g., filgrastim), or busulfan. Prior anaphylaxis with excipients of CTX001 product (Dimethyl sulfoxide [DMSO], Dextran).
16. Positive serology for the presence of human immunodeficiency virus-1 (HIV-1) 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 or nuclei acid testing [NAT tests),]), syphilis [positive screening AND confirmatory testsRPR or treponemal specific test], or hepatitis C virus (HCV positive antibody [HCAb] and NAT tests) (NAT). 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 patient and manufacturing of CTX001.
17. Participation in another clinical study with an investigational drug/product within 30 days of screening or fewer than 5 half-lives of the investigational agent, whichever is longer from screening.
18. An assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol.
19. Pregnant or breastfeeding females.

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

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