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History of Changes for Study: NCT04431219
First in Human Study: LIS1, an Induction Treatment in Kidney Transplanted Patients
Latest version (submitted April 29, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 10, 2020 None (earliest Version on record)
2 April 29, 2021 Study Status
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Study NCT04431219
Submitted Date:  June 10, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: XT-1901
Brief Title: 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
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2020
Overall Status: Recruiting
Study Start: November 26, 2019
Primary Completion: December 2020 [Anticipated]
Study Completion: December 2020 [Anticipated]
First Submitted: May 28, 2020
First Submitted that
Met QC Criteria:
June 10, 2020
First Posted: June 16, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 10, 2020
Last Update Posted: June 16, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Xenothera SAS
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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:
Open or close this module Conditions
Conditions: Kidney Transplant
Keywords: immunosuppression
polyclonal IgG
allograft transplantation
induction treatment
acute graft rejection
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
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.
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 10 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Ascending Dose Cohort

The AD cohort will be first recruited and will include 5 patients: 1 patient per dose, sequentially recruited, the recruitment of the next dose level patient will be assessed by Data Safety Monitoring Board :

  • Patient 1: 0.6 mg/Kg/day
  • Patient 2: 1 mg/Kg/day
  • Patient 3: 3 mg/Kg/day
  • Patient 4: 6 mg/Kg/day
  • Patient 5: 8 mg/Kg/day

Once the 5 AD patients complete LIS1 treatment, the sponsor and the DSMB will rule on the LIS1 dose to obtain an optimal CD3+ cells depletion, with a good safety profile and will determine the therapeutic dose.

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.
Experimental: Therapeutic Dose Cohort
The TD cohort will be recruited once the therapeutic dose is defined. This cohort will be divided in 2 subgroups of respectively 2 and 3 patients sequentially recruited. The DSMB will evaluate the accuracy of the chosen therapeutic dose safety profile after the first two patients' treatment completion and will allow the recruitment of the 3 patients of the second subgroup at the same dose, or adapt LIS1 dose for the next three patients.
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Safety of the treatment with LIS1: Blood pressure
Clinical safety parameters (1): Systolic and diastolic blood pressure (mm Hg).

[Time Frame: up to 3 months after the transplant]
2. Safety of the treatment with LIS1: Pulse rate
Clinical safety parameters (2): Pulse rate (beats per minute [bpm]) .

[Time Frame: up to 3 months after the transplant]
3. Safety of the treatment with LIS1: Body temperature
Clinical safety parameters (3): Body temperature (Celsius degrees).

[Time Frame: up to 3 months after the transplant]
4. Safety of the treatment with LIS1: Graft rejection
Clinical safety parameters (4): Graft rejection (yes/no).

[Time Frame: up to 3 months after the transplant]
5. Safety of the treatment with LIS1: Infection
Clinical safety parameters (5): Viral infections (namely Cytomegalovirus [CMV], BK virus) (yes/no).

[Time Frame: up to 3 months after the transplant]
6. Safety of the treatment with LIS1: Re-admission
Clinical safety parameters (6): Re-admission after patient discharge (yes/no).

[Time Frame: up to 3 months after the transplant]
7. Safety of the treatment with LIS1: Hospitalization
Clinical safety parameters (7): Prolonged stay in hospital for >4 weeks (days).

[Time Frame: up to 3 months after the transplant]
8. Safety of the treatment with LIS1: CRP
Laboratory parameters (1): C-Reactive Protein (CRP, mg/L).

[Time Frame: up to 3 months after the transplant]
9. Safety of the treatment with LIS1: LDH
Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L).

[Time Frame: up to 3 months after the transplant]
10. Safety of the treatment with LIS1: aPTT
Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds).

[Time Frame: up to 3 months after the transplant]
11. 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).

[Time Frame: up to 3 months after the transplant]
12. Pharmacodynamics (depletion of T lymphocytes) of LIS1
Absolute T lymphocyte counts (10^9/L).

[Time Frame: up to 3 months after the transplant]
Secondary Outcome Measures:
13. Pharmacokinetics of LIS1 (1): swine IgG
Serum concentration of swine IgG

[Time Frame: up to 3 months after the transplant]
14. Pharmacodynamics of LIS1 (2): cytokines
Cytokine concentration (IL6, TNFα) (ng/mL).

[Time Frame: up to 3 months after the transplant]
15. Biology of LIS1 (1): electrolytes plasma concentration
Plasma biochemistry: electrolytes (Na+, K+, Cl-, Ca++, Mg++, bicarbonates plasma concentrations mmol/L)

[Time Frame: up to 3 months after the transplant]
16. Biology of LIS1 (2): urea and creatinine
Plasma biochemistry: urea and creatinine plasma concentration (mmol/L)

[Time Frame: up to 3 months after the transplant]
17. Biology of LIS1 (3): total plasma proteins
Plasma biochemistry: Total protein plasma concentration (g/L)

[Time Frame: up to 3 months after the transplant]
18. 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)

[Time Frame: up to 3 months after the transplant]
19. Immunogenicity of LIS1
Detection of antidrug antibodies in serum

[Time Frame: up to 3 months after the transplant]
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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, 20-50 % 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.
Open or close this module Contacts/Locations
Central Contact Person: Bernard Vanhove, Dr
Telephone: +33(0)255 10 11 73
Email: bernard.vanhove@xenothera.com
Study Officials: Dr Ondrej Viklicky
Principal Investigator
Institut klinické a experimentální medicíny, Praha 4, Czech Republic
Locations: Czechia
Institut klinické a experimentální medicíny
[Recruiting]
Praha 4, Czechia, 140 21
Contact:Contact: Ondrej Viklicky, Prof. +420 261 365 390 ondrej.viklicky@ikem.cz
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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