Kidney Transplant
Conditions
Keywords
immunosuppression, polyclonal IgG, allograft transplantation, induction treatment, acute graft rejection
Brief summary
This first in human study aims at evaluating LIS1, a stabilized solution of purified anti-T lymphocytes polyclonal glyco-humanized swine IgG with immunosuppressive activity, in regards of safety, T cell depletion, and pharmacokinetics / pharmacodynamics in 10 kidney transplant recipients.
Interventions
BIOLOGICALLIS1
LIS1 is an induction treatment on top of maintenance immunosuppressive regimen. All patients from AD and TD cohort will receive the conventional immunosuppressive regimen: tacrolimus (0.2 mg/kg) / mycophenolic acid (MMF, 2x1000 mg) / prednisone (20 mg from day 2). This conventional treatment should be started and monitored for all patients independently of their participation in the clinical trial. Methylprednisolone 500 mg / 100 mL saline / 30 minutes will be administered before reperfusion during the surgery and on post operation day 1 just before LIS1 administration.
Sponsors
Xenothera SAS
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase I/II interventional, uncontrolled, single center, open-label study with an adaptive design conducted in two cohorts: Ascending Dose (AD) cohort and Therapeutic Dose (TD) cohort.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants must be listed for kidney transplantation, * AD cohort participants: First transplantation, Panel Reactive Antibody (PRA) \< 20%, negative Donor Specific Antibody (DSA), no anti-HLA antibodies, Epstein-Barr Virus positive (EBV+) serology, * TD cohort participants: First transplantation, 0-50 % PRA, negative DSA, negative flow cytometry crossmatch (FCXM) for any patients with anti-HLA antibodies on screening is mandatory, Epstein-Barr Virus positive (EBV+) serology * Participants must weigh at least 50 kg and have a Body Mass Index (BMI) 18.0 ≤ BMI \< 35.0 kg/m2, * White Blood Cells \> 3000/mm3, platelets \> 75000/mm3, * Female participants (WOCBP) must have a negative pregnancy test at screening and use a highly effective birth control until 90 days after the last administration of study drug, * Non-vasectomized male subjects having a female partner of childbearing potential must agree to the use of a highly effective method of contraception until 90 days after the last administration of study drug, * Participants must be capable of giving signed informed consent.
Exclusion criteria
* Patients with an active cancer or a history of kidney cancer, * Patients who have previously been exposed to other anti-lymphocyte globulins, * Patients with previous organ transplantation, * Patients with a history of specific viral infection that would contraindicate depleting antibody therapy (Hepatitis B and C, HIV), * Patients with a positive HIV and/or Hepatitis B and C tests * Patients who have uncontrolled concomitant bacterial or viral infections (unresolved during screening), mycosis and/or parasitosis, * Patients with a significant liver function impairment: enzyme (AST and/or ALT) values must not exceed 1.5 times upper limit of normal, * Patients with positive testing for tuberculosis (using QuantiFERON-TB test), Patients with CMV D+/R- constellation at transplant, * Patients with seronegative EBV prior to transplantation, * Patients who have previously been exposed to antibodies of swine origin, * Expanded Criteria Donor (ECD) defined as donor older than 60 years, * Participants who have participated in another research study involving an investigational product in the previous 3 months, * Patients with cardiovascular or severe respiratory comorbidities (severe chronic respiratory failure, severe pulmonary fibrosis, obesity-ventilation syndrome, severe idiopathic pulmonary arterial hypertension) not allowing general anesthesia, * Patients with type 1 diabetes, * Participants who are pregnant, breast feeding or planning pregnancy during the study, * Participants who have any form of substance abuse (drug, alcohol…), any other health abnormalities (psychiatric disorders) or condition that according to the investigator's opinion might endanger patient during his/her participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of the treatment with LIS1: Blood pressure | up to 3 months after the transplant | Clinical safety parameters (1): Systolic and diastolic blood pressure (mm Hg). |
| Safety of the treatment with LIS1: Pulse rate | up to 3 months after the transplant | Clinical safety parameters (2): Pulse rate (beats per minute \[bpm\]) . |
| Safety of the treatment with LIS1: Body temperature | up to 3 months after the transplant | Clinical safety parameters (3): Body temperature (Celsius degrees). |
| Safety of the treatment with LIS1: Graft rejection | up to 3 months after the transplant | Clinical safety parameters (4): Graft rejection (yes/no). |
| Safety of the treatment with LIS1: Infection | up to 3 months after the transplant | Clinical safety parameters (5): Viral infections (namely Cytomegalovirus \[CMV\], BK virus) (yes/no). |
| Safety of the treatment with LIS1: Re-admission | up to 3 months after the transplant | Clinical safety parameters (6): Re-admission after patient discharge (yes/no). |
| Safety of the treatment with LIS1: Hospitalization | up to 3 months after the transplant | Clinical safety parameters (7): Prolonged stay in hospital for \>4 weeks (days). |
| Safety of the treatment with LIS1: CRP | up to 3 months after the transplant | Laboratory parameters (1): C-Reactive Protein (CRP, mg/L). |
| Safety of the treatment with LIS1: LDH | up to 3 months after the transplant | Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L). |
| Safety of the treatment with LIS1: aPTT | up to 3 months after the transplant | Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds). |
| Safety of the treatment with LIS1: Complete Blood Count (CBC) | up to 3 months after the transplant | Laboratory parameters (4): Platelets (10\^9/L), white blood cells (10\^9/L), absolute neutrophil count (10\^9/L), absolute lymphocyte count (10\^9/L), absolute monocyte count (10\^9/L), absolute eosinophil count (10\^9/L), absolute basophil count (10\^9/L). |
| Pharmacodynamics (depletion of T lymphocytes) of LIS1 | up to 3 months after the transplant | Absolute T lymphocyte counts (10\^9/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of LIS1 (1): swine IgG | up to 3 months after the transplant | Serum concentration of swine IgG |
| Pharmacodynamics of LIS1 (2): cytokines | up to 3 months after the transplant | Cytokine concentration (IL6, TNFα) (ng/mL). |
| Biology of LIS1 (1): electrolytes plasma concentration | up to 3 months after the transplant | Plasma biochemistry: electrolytes (Na+, K+, Cl-, Ca++, Mg++, bicarbonates plasma concentrations mmol/L) |
| Biology of LIS1 (2): urea and creatinine | up to 3 months after the transplant | Plasma biochemistry: urea and creatinine plasma concentration (mmol/L) |
| Biology of LIS1 (3): total plasma proteins | up to 3 months after the transplant | Plasma biochemistry: Total protein plasma concentration (g/L) |
| Biology of LIS1 (4): plasmatic proteins | up to 3 months after the transplant | Plasma biochemistry: electrophoresis of plasmatic proteins (percentages of albumin, alpha-1-globulin, alpha-2-globulin, beta-globulin, gamma-globulin) |
| Immunogenicity of LIS1 | up to 3 months after the transplant | Detection of antidrug antibodies in serum |
Countries
Czechia
Outcome results
None listed