Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency

• Signed informed consent of the subject's legally authorized representative (in most cases, this will be the parent or parents),
• Age 1 month to 4 years,
• SCID, leaky SCID with \<100 TRECs, or Omenn syndrome requiring stem cell transplant with conditioning therapy (patients with decreased T-cell numbers by flow cytometry, decreased TREC, and decreased in vitro responses to T cell mitogens will be eligible regardless of B-cell and/or natural killer (NK) cell function),
• Identified donor (9 or 10/10 Human Leukocyte Antigen (HLA)-matched unrelated or haplocompatible relative),

• Eligible patients must have adequate physical function to tolerate the conditioning regimen and hematopoietic stem cell transplantation (HSCT), as measured by:

  • Renal function: serum creatinine ≤3x upper limit of normal for age,
  • Hepatic function: adequate synthetic function as indicated by a serum fibrinogen at or above the normal limit for the child's age,
  • Cardiac function: fractional shortening ≥30% as determined by echocardiography. (For subjects with a fractional shortening value of exactly 30%, if conditioning is delayed for any reason, a repeat echocardiogram is to be performed before the conditioning regimen is initiated to confirm the subject's continued eligibility for participation in the study.)

Exclusion Criteria:

• Lack of investigational review board (IRB) approval of the study at the treating institution,
• Lack of consent by the child's legal guardians (Israeli law requires consent by both parents),
• Adenosine deaminase (ADA) deficiency,
• The patient has a brother/sister who is a matching and available donor and who was approved to be a donor in accordance with the law and regulations,
• End-stage organ failure that precludes ability to tolerate the transplant procedure or conditioning,
• Serum creatinine >3 times upper limit of normal for age,
• Inadequate cardiac function, i.e., fractional shortening ≥30% as determined by echocardiography (for subjects with a fractional shortening value of exactly 30%, if conditioning is delayed for any reason, a repeat echocardiogram must be performed to confirm the subject's eligibility for participation in the study),
• Inadequate hepatic synthetic function indicated by serum fibrinogen below normal for the child's age or signs of hepatic failure,
• Major congenital abnormalities that adversely affect survival,
• Expected survival \<4 weeks despite transplant.

The following are NOT exclusion criteria:

• The administration of supplemental oxygen,
• The presence of infection per se, because patients with SCID frequently have infections with routine pathogens as well as opportunistic infections. Antibiotic, antifungal and antiviral prophylaxis therapy will be used as clinically indicated. Because transplantation is required for control of infections, subjects may be enrolled in the study even though infection is present although acute infections should be controlled prior to initiating transplant conditioning. Adjudication of controlled infection will be performed by the physician(s) treating the patient together with the clinical Principal Investigator of the study.