- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04431219
First in Human Study: LIS1, an Induction Treatment in Kidney Transplanted Patients
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 Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Praha 4, Czechia, 140 21
- Institut Klinicke A Experimentalni Mediciny
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 :
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. |
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.
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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. DSMB will review the safety and efficacy profile of the first 2 patients (Subgroup1) and decide:
If the decision to increase the dose after the first two TD patients is made, an additional DSMB review will be planned after patient 8. The DSMB will decide to maintain the dose for the last 2 patients or to get back to the previous dose |
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of the treatment with LIS1: Blood pressure
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (1): Systolic and diastolic blood pressure (mm Hg).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Pulse rate
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (2): Pulse rate (beats per minute [bpm]) .
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Body temperature
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (3): Body temperature (Celsius degrees).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Graft rejection
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (4): Graft rejection (yes/no).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Infection
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (5): Viral infections (namely Cytomegalovirus [CMV], BK virus) (yes/no).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Re-admission
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (6): Re-admission after patient discharge (yes/no).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Hospitalization
Time Frame: up to 3 months after the transplant
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Clinical safety parameters (7): Prolonged stay in hospital for >4 weeks (days).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: CRP
Time Frame: up to 3 months after the transplant
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Laboratory parameters (1): C-Reactive Protein (CRP, mg/L).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: LDH
Time Frame: up to 3 months after the transplant
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Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: aPTT
Time Frame: up to 3 months after the transplant
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Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds).
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up to 3 months after the transplant
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Safety of the treatment with LIS1: Complete Blood Count (CBC)
Time Frame: up to 3 months after the transplant
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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).
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up to 3 months after the transplant
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Pharmacodynamics (depletion of T lymphocytes) of LIS1
Time Frame: up to 3 months after the transplant
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Absolute T lymphocyte counts (10^9/L).
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up to 3 months after the transplant
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics of LIS1 (1): swine IgG
Time Frame: up to 3 months after the transplant
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Serum concentration of swine IgG
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up to 3 months after the transplant
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Pharmacodynamics of LIS1 (2): cytokines
Time Frame: up to 3 months after the transplant
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Cytokine concentration (IL6, TNFα) (ng/mL).
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up to 3 months after the transplant
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Biology of LIS1 (1): electrolytes plasma concentration
Time Frame: up to 3 months after the transplant
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Plasma biochemistry: electrolytes (Na+, K+, Cl-, Ca++, Mg++, bicarbonates plasma concentrations mmol/L)
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up to 3 months after the transplant
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Biology of LIS1 (2): urea and creatinine
Time Frame: up to 3 months after the transplant
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Plasma biochemistry: urea and creatinine plasma concentration (mmol/L)
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up to 3 months after the transplant
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Biology of LIS1 (3): total plasma proteins
Time Frame: up to 3 months after the transplant
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Plasma biochemistry: Total protein plasma concentration (g/L)
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up to 3 months after the transplant
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Biology of LIS1 (4): plasmatic proteins
Time Frame: up to 3 months after the transplant
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Plasma biochemistry: electrophoresis of plasmatic proteins (percentages of albumin, alpha-1-globulin, alpha-2-globulin, beta-globulin, gamma-globulin)
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up to 3 months after the transplant
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Immunogenicity of LIS1
Time Frame: up to 3 months after the transplant
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Detection of antidrug antibodies in serum
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up to 3 months after the transplant
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dr Ondrej Viklicky, Institut klinické a experimentální medicíny, Praha 4, Czech Republic
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- XT-1901
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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