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-IT
• Lead Sponsor: CRISPR Therapeutics AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-03
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Age =18 and =35 years of age.

2. Able to provide written informed consent.

3. Diagnosis of transfusion-dependent ß-thalassemia (TDT) as defined by:
a. Documented homozygous ß-thalassemia (with the exception of the ß0/ß0 genotype) 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 ß0/ß0 genotypes are defined using the HbVar Database.
b. A history of at least 100 mL/kg/year or 10 units/year of packed Red Blood Cell (RBC) transfusions in the prior 2 years before signing the consent.

4. Karnofsky performance status of =80%.

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 must agree to use effective contraception (including condoms) from start of busulfan conditioning through at least 6 months after CTX001 infusion.

9. Willing to participate in an additional long-term follow-up study or registry 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 12
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.

4. Subjects with a ß0/ß0 thalassemia genotype or 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.

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: history of relevant drug allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; or history of mental disease.

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 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 liver biopsy. Liver biopsy is required when liver iron concentration (LIC) is =15 mg/g on T2* MRI of liver. If a liver biopsy has been performed less than 6 months prior to consent, it does not need to be repeated.

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.

15. Intolerance 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 human immunodeficiency virus-1 (HIV-1) or human immunodeficiency virus-2 (HIV-2), hepatitis B virus (HBV; hepatitis B core antibody [HBcAb] and positive HBV polymerase chain reaction [PCR]), or hepatitis C virus (HCV) (positive HCV PCR). Positive serology for syphilis, toxoplasmosis or any other infectious disease marker as required by local testing for cellular processing.

17. Participation in another clinical study with an investigational drug 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