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-DE
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-07
• Last Update Posted: 9 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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 units and estimated volumes (latter if available) of packed RBCs and associated pre-transfusion Hb values, weight, and in-patient hospitalizations, for at least the 2 years prior to consent. Pre-transfusion body weight and Hb values should be collected (if available) for every transfusion.
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 (Section 3.6 of the protocol).
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. A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement.
2. Prior allogeneic HSCT.
3. Subjects with associated a-thalassemia and >1 alpha 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 count <3 × 10^9/L or platelet count <50 × 10^9/L not related to hypersplenism per investigator judgment.
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 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 on a prior liver biopsy, if available
d. Subjects with active hepatitis infection (see criterion 16).
e. Subjects with history of chronic hepatitis infection are also excluded unless liver biopsy within 3 months prior to or at screening shows no evidence of bridging fibrosis or cirrhosis
f. Liver iron content (LIC) =15 mg/g on R2* MRI of liver, unless liver biopsy within 3 months prior to or at screening shows no evidence of bridging fibrosis or cirrhosis.
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 m2.
13. Diffusion 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, GCSF 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 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 for NAT tests), syphilis [positive screening AND positive confirmatory tests (RPR or treponemal specific test)], 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 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

Study & Design

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