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

Phase 1

Completed

• Conditions: Kidney Transplant

• Registration Number: NCT04431219
• Lead Sponsor: Xenothera SAS

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-26
• Study First Submitted: 2020-05-28
• Study First Submitted QC: 2020-06-10
• Study First Posted: 2020-06-16
• Primary Completion: 2022-03-28
• Study Completion: 2022-03-28
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-16
• Last Update Posted: 2022-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Safety of the treatment with LIS1: CRP	up to 3 months after the transplant	Laboratory parameters (1): C-Reactive Protein (CRP, mg/L).
Pharmacodynamics (depletion of T lymphocytes) of LIS1	up to 3 months after the transplant	Absolute T lymphocyte counts (10\^9/L).
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: 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: aPTT	up to 3 months after the transplant	Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds).
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: 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).
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: LDH	up to 3 months after the transplant	Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L).
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: Hospitalization	up to 3 months after the transplant	Clinical safety parameters (7): Prolonged stay in hospital for \>4 weeks (days).

Secondary Outcome Measures

Name	Time	Method
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)
Pharmacodynamics of LIS1 (2): cytokines	up to 3 months after the transplant	Cytokine concentration (IL6, TNFα) (ng/mL).
Biology of LIS1 (3): total plasma proteins	up to 3 months after the transplant	Plasma biochemistry: Total protein plasma concentration (g/L)
Immunogenicity of LIS1	up to 3 months after the transplant	Detection of antidrug antibodies in serum
Pharmacokinetics of LIS1 (1): swine IgG	up to 3 months after the transplant	Serum concentration of swine IgG
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 (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)

Trial Locations

Locations (1)

Institut klinické a experimentální medicíny; 🇨🇿 Praha 4, Czechia