Liver Cell Transplant for Phenylketonuria

• Register: ClinicalTrials.gov
• Last refreshed on: 21 August 2023
• Main ID: NCT01465100
• Date of registration: 20/10/2011
• Prospective Registration: No
• Primary sponsor: Ira Fox
• Public title: Liver Cell Transplant for Phenylketonuria
• Scientific title: Hepatocyte Transplantation for Phenylketonuria
• Date of first enrolment: October 12, 2011
• Target sample size: 1
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT01465100
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Ira J Fox, MD
• Affiliation: University of Pittsburgh

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Previous diagnosis of classical PKU, as determined by a PAH mutation known to cause
classical PKU, or a Phe >20 mg/dL at any time.

2. Patients must have poor control on standard therapy (i.e. Kuvan or diet alone) as
defined by two consecutive Phe levels of > 12 mg/dL in the past six months. This is
two times the recommended level. If the patient is being treated with Palynziq, they
must discontinue treatment for at least two months before participating in this trial.

3. Baseline I.Q. =70 as assessed by Wechsler Abbreviated Scale of Intelligence (4-subtest
IQ)

4. Must have a complete evaluation, including dietary records, in a PKU clinic in the
past twelve months

5. Age between 14 and 55 years

6. Stated willingness to comply with all study procedures and availability for the
duration of the study

7. Sexually active female subjects must agree to use two highly effective forms of
contraception for the duration of the study

Exclusion Criteria:

1. I.Q. <70

2. Known biopterin synthesis defects

3. Subject has active malignancy

4. Subject has known allergy or other contraindication to immune suppression medications
(and their alternatives) required post transplant for the prevention of rejection

5. Subject has sepsis, pneumonia, other active infection, or other secondary
life-threatening organ dysfunction at Screening or Baseline Visits. Subject may be
re-screened once infection has cleared.

6. Subject is pregnant or breastfeeding

7. Subject has positive HIV serostatus

8. Liver biopsy shows significant fibrosis, defined by the Ishak Stage 5: bridges with
occasional nodules, or higher. Liver biopsy will be performed if, in the clinical
judgment of the investigators, subject has clinical signs of liver failure, or
increased risk of liver fibrosis.

9. Any condition that, in the view of the investigator, places the subject at high risk
of poor treatment compliance or not completing the required study follow-up

10. Concurrent disease or condition that would interfere with study participation or
safety



Age minimum: 14 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Phenylketonuria

Intervention(s)

Radiation: Preparative Radiation Therapy

Procedure: Liver Biopsy

Diagnostic Test: Whole body Phe oxidation testing

Procedure: Hepatocyte Transplant

Drug: Immunosuppression

Other: Liver Evaluation

Behavioral: Neuro-psychological Assessment

Primary Outcome(s)

Improvement/reversal of characteristics of PKU [Time Frame: 24 months post hepatocyte transplant]

Secondary Outcome(s)

Adaptive Behavior Assessment System-third edition (ABAS-III) [Time Frame: 6 months]

Behavior Rating Inventory of Executive Function (BRIEF-parent version) [Time Frame: 12 months]

Engraftment of Hepatocytes [Time Frame: 12 months]

Wechsler Abbreviated Scale of Intelligence-third edition (WASI-III) [Time Frame: 12 months]

Child Health Questionnaire (CHQ) [Time Frame: 12 months]

Child Health Questionnaire (CHQ) [Time Frame: 6 months]

Behavior Assessment System for Children-second edition (BASC-II) [Time Frame: 24 months]

Wechsler Abbreviated Scale of Intelligence-third edition (WASI-III) [Time Frame: 24 months]

Behavior Rating Inventory of Executive Function (BRIEF-parent version) [Time Frame: 24 months]

Child Health Questionnaire (CHQ) [Time Frame: 24 months]

Adaptive Behavior Assessment System-third edition (ABAS-III) [Time Frame: 24 months]

Behavior Assessment System for Children-second edition (BASC-II) [Time Frame: 12 months]

Beck Depression Inventory [Time Frame: 24 months]

Delis Kaplan Executive Functioning System (D-KEFS) [Time Frame: 12 months]

Behavior Assessment System for Children-second edition (BASC-II) [Time Frame: 6 months]

Behavior Rating Inventory of Executive Function (BRIEF-parent version) [Time Frame: 6 months]

Delis Kaplan Executive Functioning System (D-KEFS) [Time Frame: 6 months]

Wechsler Abbreviated Scale of Intelligence-third edition (WASI-III) [Time Frame: 6 months]

SF-36 Health Survey [Time Frame: 12 months]

SF-36 Health Survey [Time Frame: 6 months]

Connors Continuous Performance Test-third edition (CPT-III) [Time Frame: 12 months]

Engraftment of Hepatocytes [Time Frame: up to 24 months]

Beck Depression Inventory [Time Frame: 12 months]

Beck Depression Inventory [Time Frame: 6 months]

Connors Continuous Performance Test-third edition (CPT-III) [Time Frame: 24 months]

Connors Continuous Performance Test-third edition (CPT-III) [Time Frame: 6 months]

Adaptive Behavior Assessment System-third edition (ABAS-III) [Time Frame: 12 months]

Engraftment of Hepatocytes [Time Frame: 3 months]

Delis Kaplan Executive Functioning System (D-KEFS) [Time Frame: 24 months]

SF-36 Health Survey [Time Frame: 24 months]

Secondary ID(s)

STUDY19030291

Source(s) of Monetary Support

Please refer to primary and secondary sponsors