- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02860559
Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
This is a study of stem cell transplantation with TBX-1400 in pediatric subjects with severe combined immunodeficiency (SCID).
The donor cells are exposed to a protein that has been shown in the laboratory to improve the ability of the donor cells to make blood and immune cells after transplant. Exposure of the donor cells to this protein does not modify the genes in the cells in any way.
This study has two goals. The first goal is to find out if transplant with TBX-1400 is safe. The second goal is to find out what effects TBX-1400 stem cells have on time to engraftment in pediatric subjects with SCID. The study hypothesis is that TBX-1400 cells will shorten the time to immune reconstitution after transplant.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Yosef Refaeli, Dr.
- Phone Number: +1-720-859-3547
- Email: refaeli@taigabiotech.com
Study Contact Backup
- Name: Brian Turner, Dr.
- Phone Number: +1-720-859-3547
- Email: turner@taigabiotech.com
Study Locations
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-
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Jerusalem, Israel
- Hadassah Medical Center (Ein Kerem site)
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Contact:
- Polina Stepensky, Dr.
- Phone Number: +972-2-6779095
- Email: polina@hadassah.org.il
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Contact:
- Hila Yosef
- Phone Number: +972-2-6777511
- Email: hilay@hadassah.org.il
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Principal Investigator:
- Polina Stepensky, Dr.
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Petach Tikva, Israel, 4920235
- Schneider Children's Medical Center
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Contact:
- Jerry Stein, Dr.
- Phone Number: +972-3-9253657
- Email: jstein@clalit.org.il
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Contact:
- Shoshana Hanimov
- Phone Number: +972-3-9253507
- Email: shoshanaha1@clalit.org.il
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Principal Investigator:
- Jerry Stein, Dr.
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TBX-1400 treatment
Single intravenous infusion of TBX-1400
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Hematopoietic stem cells transplantation
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events following transplant with TBX-1400
Time Frame: Two years
|
Adverse events from subject or parent reporting or other assessments
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Two years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Transplant Engraftment
Time Frame: Up to Day 180
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Assessment of transplant engraftment will include analysis of T-cells , B-cells and Natural Killer cells
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Up to Day 180
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Chimerism
Time Frame: Up to Day 180
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Assessment of chimerism will include analysis of T-cells , B-cells and Natural Killer cells
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Up to Day 180
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Absolute numbers of T-cells
Time Frame: Days 30 to 360
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Days 30 to 360
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T-cell receptor excision circles (TREC)
Time Frame: Days 30 to 360.
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Days 30 to 360.
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Kappa-deleting recombination excision circles (KREC)
Time Frame: Days 30 to 360.
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Days 30 to 360.
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Immunoglobulin (Ig) levels
Time Frame: Days 30 to 360.
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Days 30 to 360.
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Immunoglobulin G (IgG) titers to pneumococcal antigens in 13-valent vaccine
Time Frame: Sixty days after final immunization
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Sixty days after final immunization
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T-cell responses to anti-CD3 and phytohemagglutinin (PHA)
Time Frame: Days 30, 60, 90, 120, and 180.
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Days 30, 60, 90, 120, and 180.
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Number of infections following transplant
Time Frame: Two years
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Two years
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Number of days granulocyte colony stimulating factor (G-CSF) was administered
Time Frame: Up to 1 year
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Up to 1 year
|
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Number of days to specific cell counts and last packed red blood cell (PRBC) transfusion
Time Frame: Up to 2 years
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Up to 2 years
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TBX-1400-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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