Phase I/II Study to Evaluate the Safety and Efficacy of JB-101(Induced T Cell With Suppressing Functions), to Induce Operational Tolerance in Living Donor Liver Transplantation.

JRCT ID: jRCT2073200067

Registered date:17/12/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Patients with end-stage liver failure undergoing living-donor liver transplantation.
• Date of first enrollment: 20/01/2020
• Target sample size: 10
• Study type: Interventional

Intervention(s)

(1) Recipient
- Lymphapheresis to collect peripheral blood mononuclear cells
- Infusion of JB-101
- Infusion of JB-CPA
- Weaning of immunosuppressive agents; Corticosteroid, Antimetabolite, Calcineurin inhibitor
(2) Donor
- Lymphapheresis to collect peripheral blood mononuclear cells

Outcome(s)

Primary Outcome

Achievement of operational tolerance
Definition of operational tolerance.
Patients who wean off immunosuppressive agents with stable liver function test by 78 (upto 91) weeks post-LDLT after JB-101 infusion are classified as operationally tolerant as long as immunosuppressive drug cessation was maintained for at least 12 months and no histopathologic evidences of acute and/or chronic rejection were observed.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

(1) Recipient
1) Patients who have given written informed consent to participate in the clinical trial.
2) Male or Female patients aged between 20 and 80 years old at the time of obtaining informed consent.
3) Patients who have been approved or will be approved for living-donor liver transplantation at the Medical Ethics Committee or equivalent organization established by the institution.
(2) Donor
1) Patients who are healthy physically and psychologically and willing to donate organs voluntarily.
2) Patients who have given written informed consent to participate in the clinical trial.
3) Relative within the second degree of relationship or partner. (Acceptable degree conforms eligibility criteria of the institution.)
4) Male or Female patients aged between 20 and 65 years old at the time of obtaining informed consent.
5) Patients who match or adapt to recipients blood type.
6) Patients who have been approved or will be approved for living-donor liver transplantation at the Medical Ethics Committee or equivalent organization established by the institution.
7) Patients who are tolerable to vessel blood access for apheresis or will be obtained informed consent for catheter insertion (Neck or Groin).

Exclude criteria

(1) Recipient
1) Patients who have clinical findings of active infection at the time of screening.
2) Patients who meet the following criteria at the time of screening.
SBP 90 or >=180 mmHg
DBP <50 or >= 100 mmHg
3) Patients who have following complications at the time of screening. (Previous medical history is acceptable.)
- Severe cardiac disease; Heart failure, Myocardial infarction, Myocarditis
- The hepatitis fulminant of the hepatic failure state.
- Renal disease; Nephrotic syndrome, Renal failure (acute and chronic), Uremia, Hydronephrosis
- Malignant neoplasm(Hepatocellular carcinoma is acceptable.)
- Immunodeficiency
4)Female who are pregnant (patients with a positive pregnancy test at screening) or are lactating during the study period. Female and male who do not agree to adequate contraception during the study period.
5) Patients who have used unapproved drugs, medical device or regenerative medical product in other clinical trial within 3 months before informed consent of the study.
6)Patients who have previous medical history of the risk factor for Torsades de pointes as follows.
- Heart failure, Hypokalemia, Family medical history of long QT syndrome; Parent, sibling, child
7) Patients who have hypersensitivity to the ingredients of Cyclophosphamide.
8) Patients who have hypersensitivity to the biological materials of investigational products; Fetal bovine serum, Ingredient derived from a rodent and human serum albumin.
9) Patients who have hypersensitivity to the ingredients of G-CSF.
10) Patients who are judged not to be appropriate in the study by principal investigators or sub-investigators.

(2) Donor
1) Patients who have following disease or state.
1.HIV antibody positive 2.HBs antigen positive 3.Creutzfeldt-Jakob disease
2) Patients who have clinical findings of active infection at the time of screening.
3) Patients who meet the following laboratory values at the time of screening.
1.Platelet < 100*10^3/uL 2.Hemoglobin < 12.0 g/dL
4) Patients who meet the following criteria at the time of screening.
SBP <90 or >=180 mmHg
DBP <50 or >= 100 mmHg
5) Patients who have following complications at the time of screening. (Previous medical history is acceptable)
- Severe cardiac disease; Heart failure, Myocardial infarction, Myocarditis
- The hepatitis fulminant of the hepatic failure state.
- Renal disease; Nephrotic syndrome, Renal failure (acute and chronic), Uremia, Hydronephrosis
6) Female who are pregnant (patients with a positive pregnancy test at screening) or are lactating during the study period.
7) Patients who have used unapproved drugs, medical device or regenerative medical product in other clinical trial within 3 months before informed consent of the study.
8) Patients who have previous medical history of the risk factor for Torsades de pointes as follows.
- Heart failure, Hypokalemia, Family medical history of long QT syndrome; Parent, sibling, child
9) Patients who are judged not to be appropriate in the study by principal investigators or sub-investigators.

Related Information

• Primary Sponsor: Uchida Koichiro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,JUNTEN BIO Co.,Ltd.
• Secondary ID(s): NCT04950842