The clinical study to evaluate the safety of the regenerative medicine and the gene therapy by the autologous transplantation of human LCAT gene transduced human pre-adipocyte

JRCT ID: jRCT2033200096

Registered date:25/08/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Familial LCAT deficiency
• Date of first enrollment: 25/08/2020
• Target sample size: 3
• Study type: Interventional
• Intervention(s): Adipose tissue is extirpated from patient with familial LCAT deficiency syndrome, and subjected to primary culture by ceiling culture. Normal LCAT gene is transduced into the obtained preadipocytes by retroviral vector-mediated gene transduction. Propagated LCAT-secreting preadipocytes are then subcutaneously transplanted into the patient.

Outcome(s)

Primary Outcome

Occurrence of adverse events which cannot be ruled out in relation to the characteristics of this clinical trial product (human preadipocytes which the LCAT gene has been introduced by ex vivo retroviral vector)
(1) Appearance of RCR after administration of clinical trial products
(2) Tumorigenesis of the administration site after administration of the clinical trial product (complementarily evaluated by the following 3 items)
(A) Malignant tumor test (TK activity)
(B) MRI examination
(C) Tumorigenicity test of the clinical trial product in immunodeficient (NSG) mice
(3) Appearance of anti-LCAT antibody after administration of clinical trial products
(4) Occurrence of unexpected serious adverse events other than (1) to (3)

Secondary Outcome

Secondary evaluation items related to safety:
(1) Type, frequency and severity of adverse events other than the main endpoints that occurred after obtaining consent
(2) Anti-FBS antibody

Secondary evaluation items related to efficacy:
Changes in blood biochemical test values are evaluated during the observation period.
(1) LCAT activity (artificial substrate method, self-substrate method, high-sensitivity activity measurement method)
(2) Blood LCAT concentration (ELISA)
(3) Cholesterylester/Total cholesterol ratio
(4) HDL-cholesterol
(5) Total-cholesterol
(6) LDL-cholesterol

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all of the following conditions.
1)Patients with a definitive diagnosis of familial LCAT deficiency based on the following diagnostic criteria
(1) LCAT gene mutation has been confirmed in genetic diagnosis (having amino acid residue substitution in LCAT protein)
(2) Low HDL-cholesterol (less than 25 mg/dL) is observed, and one or some of following complications typical for this disease is detected; corneal opacification, renal dysfunction (proteinuria), hemolytic anemia
(3) Blood LCAT activity (artificial substrate method) is below the detection limit (reference standard value 382-512U)
2)Patients older than 16.
3)Patient who provides written informed consent. If the patient is a minor, written consent must be obtained from the patient as well as a parent or guardian.

Exclude criteria

Patients who meet any of the following conditions are not included.
1)Patients who are not expected to express full-length LCAT protein due to frameshift or the appearance of stop codon by insertion/deletion mutation in LCAT gene
2)Patients whose mutant LCAT protein cannot be detected in blood by immunological method (ELISA or immunoprecipitation western blot)
3)Patients with advanced liver disease (fulminant hepatitis, cirrhosis, etc.) that affects lipid metabolism
4)Patients with advanced renal disease (transferred or planned to transfer to dialysis)
5)Patients who received LCAT protein replacement therapy by whole blood or plasma transfusion within 1 month before obtaining written consent.
6)Patients who are considered to be difficult to perform subcutaneous liposuction
7)Pregnant and lactating women. In the case of female patients who can become pregnant (all women except those who have undergone permanent contraception or those who have been postmenopausal*), those who do not agree to contraception during the clinical trial period (up to 24 weeks after administration). In addition, in the case of male patients, patients who do not agree to contraception during the clinical trial period (up to 24 weeks after administration).
8)Patients with other similar diseases that are not caused by LCAT deficiency and have low HDL-cholesterol (Apo A-1 abnormality/Tangier disease)
9)Patients with a history of hypersensitivity to the components of this clinical trial product or the components (fetal bovine serum and human albumin) used in the manufacturing process of this clinical trial product.
10)Other patients who are deemed unsuitable by the investigator or the sub-investigator

Related Information

• Primary Sponsor: Yokote Koutaro
• Secondary Sponsor: CellGenTech, Inc.
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development