Clinical trial NCT04431219: First in Human Study: LIS1, an Induction Treatment in Kidney Transplanted Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Kidney Transplant
Keywords: immunosuppression
polyclonal IgG
allograft transplantation
induction treatment
acute graft rejection
Lead sponsor: Xenothera SAS
Sponsor class: INDUSTRY
First posted: 2020-06-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety of the treatment with LIS1: Blood pressure
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Pulse rate
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Body temperature
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Graft rejection
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Infection
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Re-admission
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Hospitalization
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: CRP
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: LDH
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: aPTT
timeFrame: up to 3 months after the transplant
measure: Safety of the treatment with LIS1: Complete Blood Count (CBC)
timeFrame: up to 3 months after the transplant
measure: Pharmacodynamics (depletion of T lymphocytes) of LIS1
timeFrame: up to 3 months after the transplant
Secondary outcomes:
measure: Pharmacokinetics of LIS1 (1): swine IgG
timeFrame: up to 3 months after the transplant
measure: Pharmacodynamics of LIS1 (2): cytokines
timeFrame: up to 3 months after the transplant
measure: Biology of LIS1 (1): electrolytes plasma concentration
timeFrame: up to 3 months after the transplant
measure: Biology of LIS1 (2): urea and creatinine
timeFrame: up to 3 months after the transplant
measure: Biology of LIS1 (3): total plasma proteins
timeFrame: up to 3 months after the transplant
measure: Biology of LIS1 (4): plasmatic proteins
timeFrame: up to 3 months after the transplant
measure: Immunogenicity of LIS1
timeFrame: up to 3 months after the transplant
Other outcomes:
Locations:
city: Praha 4
country: Czechia
facility: Institut klinické a experimentální medicíny
Study officials:
affiliation: Institut klinické a experimentální medicíny, Praha 4, Czech Republic
name: Dr Ondrej Viklicky
role: PRINCIPAL_INVESTIGATOR
References: