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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02860559
• Date of registration: 26/07/2016
• Prospective Registration: Yes
• Primary sponsor: Taiga Biotechnologies, Inc.
• Public title: Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
• Scientific title: Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
• Date of first enrolment: August 2021
• Target sample size: 8
• Recruitment status: Not yet recruiting
• URL: https://clinicaltrials.gov/show/NCT02860559
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Israel

Contacts

• Name: Yosef Refaeli, Dr.

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.



Age minimum: 1 Month
Age maximum: 4 Years
Gender: All

Health Condition(s) or Problem(s) studied

Severe Combined Immunodeficiency

Intervention(s)

Biological: TBX-1400

Primary Outcome(s)

Adverse Events following transplant with TBX-1400 [Time Frame: Two years]

Secondary Outcome(s)

T-cell receptor excision circles (TREC) [Time Frame: Days 30 to 360.]

Immunoglobulin (Ig) levels [Time Frame: Days 30 to 360.]

Chimerism [Time Frame: Up to Day 180]

Immunoglobulin G (IgG) titers to pneumococcal antigens in 13-valent vaccine [Time Frame: Sixty days after final immunization]

T-cell responses to anti-CD3 and phytohemagglutinin (PHA) [Time Frame: Days 30, 60, 90, 120, and 180.]

Transplant Engraftment [Time Frame: Up to Day 180]

Kappa-deleting recombination excision circles (KREC) [Time Frame: Days 30 to 360.]

Number of days granulocyte colony stimulating factor (G-CSF) was administered [Time Frame: Up to 1 year]

Number of infections following transplant [Time Frame: Two years]

Number of days to specific cell counts and last packed red blood cell (PRBC) transfusion [Time Frame: Up to 2 years]

Absolute numbers of T-cells [Time Frame: Days 30 to 360]

Secondary ID(s)

TBX-1400-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors