IRB Study Number 23-260
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
Evaluate the safety and tolerability of treatment with EDIT-301 in adult participants with TDT
Secondary Objectives
Evaluate the fate of EDIT-301 post-administration
Evaluate post-administration pharmacodynamic properties of EDIT-301
Evaluate the preliminary efficacy of EDIT-301
Assess the effects of EDIT-301 infusion on disease specific events
Inclusion Criteria
Male and female participants age 18 to 35 years
Diagnosis of Transfusion-Dependent Beta Thalassemia (TDT) as defined by:
a. Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE) based on historical data in medical records, and
b. History of at least 100 mL/kg/year or 10 U/year of packed RBC transfusions in the 2 years prior to signing informed consent
Clinically stable and eligible to undergo autologous HSCT
Access to detailed medical records documenting transfusion history, hemoglobin (Hb) values, and hospitalization for 2 years prior to signing informed consent
Karnofsky Performance Status ≥ 70
Male and female participants of childbearing potential (FCBP) must agree to use acceptable method(s) of contraception starting at screening and for at least 6 months post- EDIT-301 infusion
• A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, 3) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months), or 4) has had no menses due to hypogonadism
Must be willing to participate in an additional 13-year long-term follow up study after completion of this study.
Capable of providing written Informed Consent prior to any screening procedures
Exclusion Criteria
Participation in another clinical study with an investigational agent within 30 days of screening or fewer than 5 half-lives of the investigational agent, whichever is longer
Nucleotide polymorphisms at the HBG1 and HBG2 promotor sequence not recognized by the synthetic oligonucleotide guide, as determined by the sequencing of the participant’s deoxyribonucleic acid (DNA) during screening
Prior receipt of gene therapy
Participants with associated a history of α-thalassemia and > 1 alpha chain deletion, or alpha multiplications as documented in medical records
Participants with a history of other inherited hemoglobinopathy or thalassemic mutation (Hb S, C, D or other) as documented in medical records
Available 10/10 HLA-matched related donor
Prior HSCT or contraindications to autologous HSCT
Inadequate bone marrow function, as defined by white blood cell count of < 3 x 109/L or a platelet count < 100 x 109/L (without hypersplenism), per investigator judgement
Any contraindications to the use of plerixafor or G-CSF during the mobilization of hematopoietic stem cells (HSCs) or any contraindications to the use of busulfan and any other medicinal products required during myeloablative conditioning
Prior hypersensitivity with the excipients or any of the components of EDIT-301 (e.g. dimethyl sulfoxide [DMSO])
History of alloimmunization and significantly challenging to obtain compatible red blood cell (RBC) for transfusions in the investigator’s judgement
History of a significant bleeding disorder
Unable or unwilling to comply with standard of care changes in background medical treatment in preparation of, during, or following HSCT
History of cirrhosis or any evidence of bridging fibrosis, or active hepatitis on previous liver biopsy
Inadequate organ function demonstrated by:
a. Cardiac function: cardiac T2* <10 ms by MRI, or left ventricular ejection fraction < 45% or LV shortening < 26% by echocardiogram or MUGA
b. Pulmonary function: diffusing capacity of lung for carbon monoxide ≤ 50% (corrected for Hb and/or alveolar volume) or baseline pulse oximetry O2 saturation < 90%
c. Renal function: Estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m2
d. Liver function defined as:
i. Persistent aspartate transaminase (AST) or alanine transaminase (ALT) > 3 x ULN, or direct bilirubin value > 3.0 x ULN, or
ii. Liver iron content (LIC) ≥ 15 mg/g on R2* MRI of liver, or
iii. PT (INR) or PTT > 1.5 x ULN. INR between 2 – 3 allowed for participants receiving anticoagulant therapy
Any prior or current malignancy, or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin (greater than or equal to 5 years post-cure based on medical history)
Immediate family member with a known or suspected Familial Cancer Syndrome
Diagnosis of significant psychiatric disorder of the participant that, in the Investigator's judgment, could seriously impede the ability to participate in the study
Clinically significant and active or recent (within 30 days) bacterial, viral, fungal, or parasitic infection that could pose additional risk to the participant’s HSCT
Positive for presence of human immunodeficiency virus (HIV) type 1 or 2, hepatitis B virus (HBV), or hepatitis C virus (HCV)
a. Participants who test positive for HBV core antibody or HCV antibody must have documentation of negative viral assays by polymerase chain reaction (PCR)
b. Presence of hepatitis B surface antibody alone does not exclude a participant
Pregnancy or breastfeeding in a postpartum female
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 product to the participant. 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 uncontrolled seizure disorders
