First in Human Study: LIS1, an Induction Treatment in Kidney Transplanted Patients

Kidney Transplant Clinical Trial

Official title:

First in Human Study for the Assessment of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Multiple Ascending Intravenous Doses of LIS1 in Kidney Transplanted Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04431219
• Other study ID #: XT-1901
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 26, 2019
• Est. completion date: March 28, 2022

Study information

• Verified date: August 2022
• Source: Xenothera SAS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 28, 2022
• Est. primary completion date: March 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Biological:
• LIS1
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.

Locations

Country	Name	City	State
Czechia	Institut klinické a experimentální medicíny	Praha 4

Sponsors (1)

Lead Sponsor	Collaborator
Xenothera SAS

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of the treatment with LIS1: Blood pressure	Clinical safety parameters (1): Systolic and diastolic blood pressure (mm Hg).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Pulse rate	Clinical safety parameters (2): Pulse rate (beats per minute [bpm]) .	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Body temperature	Clinical safety parameters (3): Body temperature (Celsius degrees).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Graft rejection	Clinical safety parameters (4): Graft rejection (yes/no).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Infection	Clinical safety parameters (5): Viral infections (namely Cytomegalovirus [CMV], BK virus) (yes/no).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Re-admission	Clinical safety parameters (6): Re-admission after patient discharge (yes/no).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Hospitalization	Clinical safety parameters (7): Prolonged stay in hospital for >4 weeks (days).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: CRP	Laboratory parameters (1): C-Reactive Protein (CRP, mg/L).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: LDH	Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: aPTT	Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds).	up to 3 months after the transplant
Primary	Safety of the treatment with LIS1: Complete Blood Count (CBC)	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).	up to 3 months after the transplant
Primary	Pharmacodynamics (depletion of T lymphocytes) of LIS1	Absolute T lymphocyte counts (10^9/L).	up to 3 months after the transplant
Secondary	Pharmacokinetics of LIS1 (1): swine IgG	Serum concentration of swine IgG	up to 3 months after the transplant
Secondary	Pharmacodynamics of LIS1 (2): cytokines	Cytokine concentration (IL6, TNFa) (ng/mL).	up to 3 months after the transplant
Secondary	Biology of LIS1 (1): electrolytes plasma concentration	Plasma biochemistry: electrolytes (Na+, K+, Cl-, Ca++, Mg++, bicarbonates plasma concentrations mmol/L)	up to 3 months after the transplant
Secondary	Biology of LIS1 (2): urea and creatinine	Plasma biochemistry: urea and creatinine plasma concentration (mmol/L)	up to 3 months after the transplant
Secondary	Biology of LIS1 (3): total plasma proteins	Plasma biochemistry: Total protein plasma concentration (g/L)	up to 3 months after the transplant
Secondary	Biology of LIS1 (4): plasmatic proteins	Plasma biochemistry: electrophoresis of plasmatic proteins (percentages of albumin, alpha-1-globulin, alpha-2-globulin, beta-globulin, gamma-globulin)	up to 3 months after the transplant
Secondary	Immunogenicity of LIS1	Detection of antidrug antibodies in serum	up to 3 months after the transplant