Thymus Transplantation Dose in DiGeorge #932

• Sponsor: Enzyvant Therapeutics GmBH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00576836
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 7
• Location: 1
• Arms: 2
• Actual Duration (Months): 183.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

One purpose of this study is to determine whether the amount of cultured thymus tissue implanted into DiGeorge anomaly infants has any effect on the immune outcome. Another purpose of this study is to determine whether parental parathyroid transplantation (in addition to cultured thymus tissue implantation (CTTI) can help both the immune and the calcium problems in DiGeorge infants with hypocalcemia. [Funding Source - FDA Office of Orphan Products Development (OOPD)]

Condition or Disease	Intervention/Treatment	Phase
DiGeorge Anomaly; DiGeorge Syndrome; Complete DiGeorge Anomaly; Complete DiGeorge Syndrome	Biological: Cultured Thymus Tissue Implantation (CTTI); Other: Cultured Thymus Tissue Implantation with Parathyroid Transplantation	Phase 2

Detailed Description

DiGeorge anomaly is a congenital disorder in which infants are born with defects of the thymus, heart, and parathyroid gland. Complete DiGeorge Anomaly is usually fatal within the first two years of life. This trial evaluates the role of cultured thymus tissue dose in cultured thymus tissue implantation (CTTI) in complete (typical) DiGeorge anomaly infants, and continues safety assessments.

DiGeorge infants who have successful CTTIs but remain with hypoparathyroidism must go to the clinic for frequent calcium levels and to the hospital for calcium infusions; these infants are at risk for seizures from low calcium. Approximately ½ of infants with profound hypoparathyroidism will develop nephrocalcinosis. This protocol had a parental parathyroid transplant arm for complete DiGeorge infants with athymia and profound hypoparathyroidism.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dose Study of Thymus Transplantation in DiGeorge Anomaly, IND 9836, #932.1
• Actual Study Start Date: Sep 2, 2004
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cultured Thymus Tissue Implantation w Parathyroid Transplant Cultured Thymus Tissue Implantation With Parathyroid Tissue Transplantation. Subjects who were enrolled in this arm underwent cultured thymus tissue implantation with parathyroid transplantation, if eligible. No specific dose was assigned. The thymus tissue dose was the number of grams of cultured thymus tissue divided by the weight of the recipient in kg or per square meter of body surface area of the recipient. There was a one time administration of the cultured thymus tissue and parathyroid tissue.	Other: Cultured Thymus Tissue Implantation with Parathyroid Transplantation; Parental parathyroid donors screened for eligibility and safety. If both parents meet eligibility criteria, the parathyroid will be harvested from parent who shares the most Human Leukocyte Antigens (HLA) alleles with thymus donor. Parathyroid harvest & transplant preferably done at same time as CTTI. (If parathyroid transplant cannot be done at same time, then it is done within 3-8 weeks of CTTI.) Parathyroid harvest done under general anesthesia. One parathyroid gland is minced & placed in quadriceps muscle; there is no dose in mg. No biopsy done of the parathyroid. Parathyroid donors are monitored as outpatients until recipients' discharge. Recipients' calcium and PTH levels are monitored indefinitely.; Other Names: Thymus and Parathyroid Transplant CTTI and Parathyroid Transplant
Experimental: Cultured Thymus Tissue Implantation Cultured Thymus Tissue Implantation. Subjects who were enrolled in this arm underwent cultured thymus tissue implantation (CTTI) only. No specific dose was assigned. The thymus tissue dose was the number of grams of cultured thymus tissue divided by the weight of the recipient in kg or per square meter of body surface area of the recipient. There was a one time administration of the cultured thymus tissue. .	Biological: Cultured Thymus Tissue Implantation (CTTI); Thymus tissue (from unrelated donor), thymus donor, and thymus donor's birth mother screened for safety. CTTI was done under general anesthesia. Cultured thymus tissue was implanted into quadriceps. Thymus dose at least 4grams/m2 body surface area (0.2 grams/kg body weight) and not >18 grams/m2 body surface area (1.0 grams/kg body weight). At time of CTTI, skin biopsy was obtained to look for preexisting T cells. 2-3 months post-CTTI allograft biopsy was done to evaluate for thymopoiesis & graft rejection. At time of biopsy, skin biopsy done to look for T cell clonal populations. (Allograft biopsy not done if subject medically unstable.) Post-CTTI, subjects followed by immune evaluations, using blood samples.; Other Names: Thymus Tissue for Transplantation CTTI

Outcome Measures

Primary Outcome Measures

1. Survival at 1 Year Post-CTTI [1 year post-CTTI]

   Survival at 1 year post CTTI was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.

Secondary Outcome Measures

1. Survival at 2 Years Post-CTTI [2 years post-CTTI]

   Survival at 2 years post CTTI was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.

2. Immune Reconstitution Efficacy - CD3 T Cells [1 year post-CTTI]

   The development of total CD3 T cells at one year as measured using flow cytometry

3. Immune Reconstitution Efficacy - CD4 T Cells [1 year post-CTTI]

   The development of total CD4 T cells at one year as measured using flow cytometry

4. Immune Reconstitution Efficacy - CD8 T Cells [1 year post-CTTI]

   The development of total CD8 T cells at one year as measured using flow cytometry

5. Immune Reconstitution Efficacy - Naive CD4 T Cells [1 year post-CTTI]

   The development of naive CD4 T cells at one year as measured using flow cytometry

6. Immune Reconstitution Efficacy - Naive CD8 T Cells [1 year post-CTTI]

   The development of naïve CD8 T cells at one year as measured using flow cytometry.

7. Immune Reconstitution Efficacy - Response to Mitogens [1 year post-CTTI]

   The development of a T cell proliferative response to the mitogen phytohemagglutinin.

8. Thymus Allograft Biopsy [2 to 3 months post-CTTI]

   Evidence, on biopsy of the thymus tissue implanted in the recipient muscle, that shows the development of new T cells.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Thymus Transplant Inclusion Criteria:

• A parent or guardian of the DGS subject signed the consent form.

• Medical screening was completed.

• For a diagnosis of DGS, the subject had to have one of the following:

• Congenital heart disease;

• Hypocalcemia requiring replacement;

• 22q11.2 hemizygosity or 10p13 hemizygosity;

• CHARGE association or CHD7 mutation;

• A subject with abnormal ears whose mother had diabetes (type I, type II, or gestational).

• To meet the criteria of typical complete DiGeorge Anomaly (cDGA), the subject had to have either:

• Circulating CD3+ T cell count by flow cytometry < 50/mm3 OR

• Circulating CD3+ T cells that were also positive for Cluster of Differentiation 45RA (CD45RA)+ CD62L+ and were < 50/mm3 or less than 5% of total T cells.

Thymus Transplant Exclusion Criteria:

• Had heart surgery less than 4 weeks prior to projected implant date;

• Heart surgery anticipated within 3 months after the proposed time of implantation;

• Present or past lymphadenopathy;

• Rash associated with T cell infiltration of the dermis and epidermis;

• Rejection by the surgeon or anesthesiologist as surgical candidate;

• Lack of sufficient muscle tissue to accept a transplant of 4 g/m2 body surface area (BSA) or 0.2 g/kg subject bodyweight;

• Had human immunodeficiency virus (HIV) infection;

• Had prior attempts at immune reconstitution, such as bone marrow transplant or previous thymus transplantation;

• Ventilator support or positive pressure support: Subjects had to be off ventilator or other pressure support such as continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) support for 2 weeks prior to enrollment. If the subject was enrolled and was placed back on ventilator or pressure support, the subject had to be able to be weaned off and remain off ventilator or pressure support for 2 weeks. If the subject could not be successfully weaned off ventilator or pressure support, the subject was to be withdrawn from the study.

Additional Inclusion Criteria for Parathyroid Transplant Recipient:

• 2 tests in patient showing: intact parathyroid hormone (PTH) < 5 pg/ml when ionized calcium < 1.1 mmol/L

• All inclusion criteria for thymus transplant must be met

• 2 involved parents

Exclusion for Parathyroid Transplant Recipient:

• Parents do not meet enrollment criteria.

• Parent(s) decline to be parathyroid donor(s).

Parental Parathyroid Donor Inclusion:

• 18 years old

• Answers all questionnaire items and meets safety screening criteria

• Normal serum calcium

• Normal PTH function

• HLA typing consistent with parentage

• Parent chosen for donation will share HLA-DR allele in thymus donor; if not applicable, then either parent will be selected (if meet all other criteria).

• Must not be on anticoagulation or can come off for donation/transplantation

Parental Parathyroid Donor Exclusion:

• Donor is only living involved parent or caretaker of the recipient

• Hypoparathyroidism - low parathyroid hormone (PTH) in presence of low serum calcium and high serum phosphate

• Hyperparathyroidism (or history of) - elevated PTH in presence of high serum calcium and low serum phosphate

• History of cancer

• Evidence of any of following: HIV-1, HIV-2, HTLV-1, HTLV-2, syphilis, hepatitis B, hepatitis C, West Nile virus, or Trypanosoma Cruzi (Chagas disease)

• Elevated AST, ALT, alkaline phosphatase > 3 times upper limit of normal

• History including receipt of a xenograft or risk factors for SARS, Mad Cow - Disease or smallpox. Note: if parent has Mad Cow Disease risk factors (but not active disease), parent(s) may give permission for transplantation.

• CMV positive urine

• Positive CMV IgM antibodies

• Positive IgM anti-EBV VCA

• On blood thinners and cannot stop for the parathyroid donation

• Elevated PT or PTT (> ULN)

• Platelets < 100,000

• Positive Toxoplasma IgM

• The donor will receive a history and physical; may be excluded based on PI's medical judgment

• Hemoglobin < 9 g/dl

• Infectious lesion on head or neck

• Goiter on ultrasound

• Abnormal fiberoptic laryngoscopy of vocal cords

• Pregnancy

• Positive HSV IgG is not an exclusion; however, post transplantation prophylaxis is needed

• Positive VZV IgG is not an exclusion; however, post transplantation prophylaxis is needed

• Medical concern of otolaryngologist

• Concern by medical psychologist or social worker. Parents are interviewed together and separately regarding following areas: medical history; health habits; substance use; relationships and support; education/work history; mental status/psychological history; readiness for donation.

• Questionnaire (safety screening) responses can lead to exclusion.

Biological Mother of DiGeorge Subject Inclusion Criteria:

• Competent to provide consent

• Willing to provide blood for testing (No other inclusion/exclusion for mother)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Enzyvant Therapeutics GmBH
• National Institutes of Health (NIH)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: M. Louise Markert, MD, PhD, Duke University Medical Center, Pediatrics, Allergy & Immunology

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chinn IK, Devlin BH, Li YJ, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008 Mar;126(3):277-81. Epub 2007 Dec 26.
• Chinn IK, Milner JD, Scheinberg P, Douek DC, Markert ML. Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3- T cells in complete DiGeorge anomaly. Clin Exp Immunol. 2013 Jul;173(1):140-9. doi: 10.1111/cei.12088.
• Chinn IK, Olson JA, Skinner MA, McCarthy EA, Gupton SE, Chen DF, Bonilla FA, Roberts RL, Kanariou MG, Devlin BH, Markert ML. Mechanisms of tolerance to parental parathyroid tissue when combined with human allogeneic thymus transplantation. J Allergy Clin Immunol. 2010 Oct;126(4):814-820.e8. doi: 10.1016/j.jaci.2010.07.016. Epub 2010 Sep 15.
• Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-30. Epub 2003 Apr 17.

• Responsible Party: Enzyvant Therapeutics GmBH
• ClinicalTrials.gov Identifier: NCT00576836
• Other Study ID Numbers: Pro00016144; FDA-FD-R-002606; 2R01AI047040-11A2; R56 Bridge R01AI4704011A1; 5K12HD043494-09; R01AI054843; R01AI047040; 3R56AI047040-11A1S1; 932
• First Posted: Dec 19, 2007
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Enzyvant Therapeutics GmBH: Thymus Transplantation; DiGeorge Syndrome; DiGeorge Anomaly; Athymia; Parathyroid Transplantation; Hypocalcemia; Hypoparathyroidism; Low T cell numbers; Immunoreconstitution; Immunodeficiency; Complete DiGeorge; Complete DiGeorge Anomaly; Typical DiGeorge; Cultured Thymus Tissue Implantation (CTTI)
• Additional relevant MeSH terms: DiGeorge Syndrome; Congenital Abnormalities; Syndrome; Parathyroid Hormone

Study Results

Participant Flow

Pre-assignment Detail	The goal of this study is survival of subjects after cultured thymus tissue implantation (CTTI) regardless of parathyroid co-transplantation. No subject underwent CTTI with parathyroid transplant.

Arm/Group Title	Cultured Thymus Tissue Implantation w Parathyroid Transplant	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI): Thymus tissue (from unrelated donor), thymus donor and thymus donor's birth mother screened for safety. CTTI done under general anesthesia. Cultured thymus tissue is implanted into quadriceps. Thymus dose at least 4grams/m2 body surface area (0.2 grams/kg body weight) and not >18 grams/m2 body surface area (1.0 grams/kg body weight). At time of CTTI, skin biopsy is obtained to look for preexisting T cells. 2-3 months post-CTTI allograft biopsy done to evaluate for thymopoiesis & graft rejection. At time of biopsy, skin biopsy done to look for T cell clonal populations. Allograft biopsy not done if subject medically unstable. Post-CTTI, subjects followed by immune evaluations, using blood samples. Parathyroid Tissue for Transplantation: If both parents meet eligibility criteria, the parent chosen for donation will be the one sharing the parental HLA (Human Leukocyte Antigen)-DR allele that is not in the recipient but is in the thymus donor.	Cultured Thymus Tissue Implantation (CTTI): Thymus tissue (from unrelated donor), thymus donor, and thymus donor's birth mother screened for safety. CTTI is done under general anesthesia. Cultured thymus tissue is implanted into quadriceps. Cultured thymus tissue dose at least 4grams/m2 body surface area (0.2 grams/kg body weight) and not >18 grams/m2 body surface area (1.0 grams/kg body weight). At time of CTTI, skin biopsy obtained to look for preexisting T cells. 2-3 months post-CTTI allograft biopsy done to evaluate for thymopoiesis & graft rejection. At time of biopsy, skin biopsy is done to look for T cell clonal populations. (Allograft biopsy not done if subject medically unstable.) Post-CTTI, subjects followed by immune evaluations, using blood samples.
Period Title: Overall Study
STARTED	0	7
COMPLETED	0	5
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Overall Participants	7
Age (Count of Participants)
<=18 years	7 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	316 (182)
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 28.6%
Not Hispanic or Latino	5 71.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 14.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 14.3%
White	5 71.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Survival at 1 Year Post-CTTI
Description	Survival at 1 year post CTTI was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Analysis includes cDGA participants. After CTTI, 1 subject was determined to have SCID and not cDGA. Efficacy analysis as reported is on cDGA, without the SCID subject as CTTI cannot lead to T cell development in SCID. No subjects were enrolled into Arm 1. No subjects received parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	6
Number (95% Confidence Interval) [% of participants who survive to 1 year]	83 1185.7%

2. Secondary Outcome

Title	Survival at 2 Years Post-CTTI
Description	Survival at 2 years post CTTI was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.
Time Frame	2 years post-CTTI

Outcome Measure Data

Analysis Population Description

Analysis includes cDGA participants. After CTTI, 1 subject was determined to have SCID and not cDGA. Efficacy analysis as reported is on cDGA, without the SCID subject as CTTI cannot lead to T cell development in SCID. No subjects were enrolled into Arm 1. No subjects received parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	6
Number (97.5% Confidence Interval) [% of participants who survive to 2 years]	83 1185.7%

3. Secondary Outcome

Title	Immune Reconstitution Efficacy - CD3 T Cells
Description	The development of total CD3 T cells at one year as measured using flow cytometry
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Data were only included on cDGA participants for the 1 year time point if a CD3 T cell count was performed in the relevant time period. The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	4
Median (Inter-Quartile Range) [cells/mm3]	635

4. Secondary Outcome

Title	Immune Reconstitution Efficacy - CD4 T Cells
Description	The development of total CD4 T cells at one year as measured using flow cytometry
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Data were only included on cDGA participants for the 1 year time point if a CD4 T cell count was performed in the relevant time period. The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	4
Median (Inter-Quartile Range) [cells/mm3]	499

5. Secondary Outcome

Title	Immune Reconstitution Efficacy - CD8 T Cells
Description	The development of total CD8 T cells at one year as measured using flow cytometry
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Data were only included on cDGA participants for the 1 year time point if a CD8 T cell count was performed in the relevant time period. The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	4
Median (Inter-Quartile Range) [cells/mm3]	116

6. Secondary Outcome

Title	Immune Reconstitution Efficacy - Naive CD4 T Cells
Description	The development of naive CD4 T cells at one year as measured using flow cytometry
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Data were only included on cDGA participants for the 1 year time point if a T cell count was performed in the relevant time period. The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	4
Median (Inter-Quartile Range) [cells/mm3]	279

7. Secondary Outcome

Title	Immune Reconstitution Efficacy - Naive CD8 T Cells
Description	The development of naïve CD8 T cells at one year as measured using flow cytometry.
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Data were only included on cDGA participants for the 1 year time point if a T cell count was performed in the relevant time period. The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	2
Median (Inter-Quartile Range) [cells/mm3]	214

8. Secondary Outcome

Title	Immune Reconstitution Efficacy - Response to Mitogens
Description	The development of a T cell proliferative response to the mitogen phytohemagglutinin.
Time Frame	1 year post-CTTI

Outcome Measure Data

Analysis Population Description

Data were only included on cDGA participants for the 1 year time point if testing was performed in the relevant time period. The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	4
Median (Inter-Quartile Range) [counts per minute (cpm)]	135016

9. Secondary Outcome

Title	Thymus Allograft Biopsy
Description	Evidence, on biopsy of the thymus tissue implanted in the recipient muscle, that shows the development of new T cells.
Time Frame	2 to 3 months post-CTTI

Outcome Measure Data

Analysis Population Description

cDGA participants who had a biopsy on the thymus tissue implanted.The study was designed to assess survival. No subjects were enrolled into Arm 1. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 2 only.

Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
Measure Participants	2
Evidence of thymopoiesis	1 14.3%
Evidence of rejection	0 0%
Inconclusive for thymopoiesis	1 14.3%

Adverse Events

Time Frame	Two years post-CTTI
Adverse Event Reporting Description	AE reporting on all participants (cDGA and SCID) who received cultured thymus tissue Implantation (CTTI) (previously described as transplantation). No participants received CTTI with a Parathyroid Transplant.
Arm/Group Title	Cultured Thymus Tissue Implantation
Arm/Group Description	Cultured Thymus Tissue Implantation (CTTI) (previously described as transplantation) is done using allogenic cultured postnatal tissue from unrelated donors.
All Cause Mortality
	Cultured Thymus Tissue Implantation
	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)
Serious Adverse Events
	Cultured Thymus Tissue Implantation
	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia	1/7 (14.3%)	1
Haemolysis	1/7 (14.3%)	1
Neutropenia	1/7 (14.3%)	1
Thrombocytopenia	1/7 (14.3%)	1
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	1/7 (14.3%)	1
Gastrointestinal disorders
Abdominal distension	1/7 (14.3%)	1
Diarrhoea	1/7 (14.3%)	1
Gastrointestinal haemorrhage	1/7 (14.3%)	1
General disorders
Pyrexia	3/7 (42.9%)	5
Immune system disorders
Hypersensitivity	1/7 (14.3%)	2
Graft versus host disease	1/7 (14.3%)	1
Graft versus host disease in gastrointestinal tract	1/7 (14.3%)	1
Infections and infestations
Device related infection	4/7 (57.1%)	12
Pneumonia	2/7 (28.6%)	2
Respiratory tract infection bacterial	1/7 (14.3%)	2
Adenoviral upper respiratory infection	1/7 (14.3%)	1
Brain abscess	1/7 (14.3%)	1
Enterobacter bacteraemia	1/7 (14.3%)	1
Enterococcal bacteraemia	1/7 (14.3%)	1
Liver abscess	1/7 (14.3%)	1
Lower respiratory tract infection	1/7 (14.3%)	1
Lower respiratory tract infection bacterial	1/7 (14.3%)	1
Otitis media	1/7 (14.3%)	1
Pneumonia klebsiella	1/7 (14.3%)	1
Pneumonia pseudomonal	1/7 (14.3%)	1
Viral upper respiratory tract infection	1/7 (14.3%)	1
Injury, poisoning and procedural complications
Transfusion reaction	1/7 (14.3%)	1
Investigations
Lymphocyte count abnormal	1/7 (14.3%)	1
Metabolism and nutrition disorders
Electrolyte imbalance	1/7 (14.3%)	1
Nervous system disorders
Central nervous system haemorrhage	1/7 (14.3%)	1
Renal and urinary disorders
Renal failure	1/7 (14.3%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/7 (42.9%)	3
Respiratory failure	2/7 (28.6%)	2
Pulmonary oedema	1/7 (14.3%)	1
Wheezing	1/7 (14.3%)	1
Vascular disorders
Hypotension	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Cultured Thymus Tissue Implantation
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Blood and lymphatic system disorders
Anaemia	3/7 (42.9%)	4
Cardiac disorders
Sinus tachycardia	2/7 (28.6%)	3
Ventricular extrasystoles	1/7 (14.3%)	1
Ventricular tachycardia	1/7 (14.3%)	1
Ear and labyrinth disorders
Deafness	1/7 (14.3%)	1
Middle ear effusion	1/7 (14.3%)	1
Endocrine disorders
Cushingoid	1/7 (14.3%)	1
Eye disorders
Retinal haemorrhage	1/7 (14.3%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	2/7 (28.6%)	2
Gastrooesophageal reflux disease	2/7 (28.6%)	2
Diarrhoea	1/7 (14.3%)	2
Abdominal distension	1/7 (14.3%)	1
Retching	1/7 (14.3%)	1
Vomiting	1/7 (14.3%)	1
General disorders
Pyrexia	4/7 (57.1%)	10
Catheter site erosion	1/7 (14.3%)	1
Hepatobiliary disorders
Cholestasis	1/7 (14.3%)	1
Hepatic lesion	1/7 (14.3%)	1
Hepatitis	1/7 (14.3%)	1
Infections and infestations
Pneumonia pseudomonal	2/7 (28.6%)	3
Urinary tract infection enterococcal	2/7 (28.6%)	2
Lower respiratory tract infection bacterial	1/7 (14.3%)	4
Clostridium difficile colitis	1/7 (14.3%)	1
Cystitis escherichia	1/7 (14.3%)	1
Ear infection	1/7 (14.3%)	1
Enterobacter pneumonia	1/7 (14.3%)	1
Oropharyngeal candidiasis	1/7 (14.3%)	1
Parainfluenzae virus infection	1/7 (14.3%)	1
Pneumocystis jirovecii pneumonia	1/7 (14.3%)	1
Sinusitis bacterial	1/7 (14.3%)	1
Stoma site infection	1/7 (14.3%)	1
Upper respiratory tract infection bacterial	1/7 (14.3%)	1
Urinary tract infection bacterial	1/7 (14.3%)	1
Urinary tract infection fungal	1/7 (14.3%)	1
Urinary tract infection pseudomonal	1/7 (14.3%)	1
Viraemia	1/7 (14.3%)	1
Viral upper respiratory tract infection	1/7 (14.3%)	1
Injury, poisoning and procedural complications
Wound complication	1/7 (14.3%)	1
Investigations
Alanine aminotransferase increased	3/7 (42.9%)	3
Aspartate aminotransferase increased	3/7 (42.9%)	3
Blood bilirubin increased	2/7 (28.6%)	2
International normalised ratio increased	2/7 (28.6%)	2
Activated partial thromboplastin time prolonged	1/7 (14.3%)	1
Amylase increased	1/7 (14.3%)	1
Blood alkaline phosphatase increased	1/7 (14.3%)	1
Blood bicarbonate decreased	1/7 (14.3%)	1
Blood urea increased	1/7 (14.3%)	1
Urine electrolytes abnormal	1/7 (14.3%)	1
pH urine increased	1/7 (14.3%)	1
Metabolism and nutrition disorders
Feeding intolerance	2/7 (28.6%)	3
Hyperkalaemia	1/7 (14.3%)	1
Hypernatraemia	1/7 (14.3%)	1
Hypertriglyceridaemia	1/7 (14.3%)	1
Hypocalcaemia	1/7 (14.3%)	1
Hypokalaemia	1/7 (14.3%)	1
Hypomagnesaemia	1/7 (14.3%)	1
Lactase deficiency	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Osteoporosis	1/7 (14.3%)	1
Nervous system disorders
Seizure	2/7 (28.6%)	2
Tremor	2/7 (28.6%)	2
Peripheral motor neuropathy	1/7 (14.3%)	1
Vocal cord paralysis	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/7 (28.6%)	2
Respiratory failure	1/7 (14.3%)	1
Wheezing	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Drug eruption	1/7 (14.3%)	1
Eczema	1/7 (14.3%)	1
Skin disorder	1/7 (14.3%)	1
Vascular disorders
Hypertension	2/7 (28.6%)	2
Hypotension	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.