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Kidney TransplantPhase 1/2NCT04431219

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

A Phase 1/2 study testing LIS1 in people with Kidney Transplant, run by Xenothera SAS at 1 site in Czechia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Kidney Transplant
What is being tested?
LIS1
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteCzechia
Study dates
26 Nov 2019to 28 Mar 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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,
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  • 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.

Trial locations and contacts

1 site in 1 country.

Czechia1 site

  • Institut klinické a experimentální medicíny

    Prague, 140 21

Other trials in Czechia

About this study

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

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.

Being tested
LIS1
Keywords
immunosuppression, polyclonal IgG, allograft transplantation, induction treatment, acute graft rejection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LIS1Biological

    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.

Study groups in NCT04431219
Study groupRoleWhat they receive
Ascending Dose CohortExperimentalThe 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.
Receives: Biological: LIS1
Therapeutic Dose CohortExperimentalThe 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: * To continue at the same dose and recruit the next 3 patients of Subgroup 2 * To recruit the next 3 patients with a lower dose, estimated from AD as bringing efficient depletion * To recruit the next patient with a higher dose (+2 mg/kg), if the depletion is not considered satisfactory and if the safety profile is considered acceptable * To end the trial if LIS1 toxicity is too important vs its efficacy in CD3+ depletion. 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
Receives: Biological: LIS1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of the treatment with LIS1: Blood pressure

    Clinical safety parameters (1): Systolic and diastolic blood pressure (mm Hg).

    Measured: 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]) .

    Measured: up to 3 months after the transplant

  3. Safety of the treatment with LIS1: Body temperature

    Clinical safety parameters (3): Body temperature (Celsius degrees).

    Measured: up to 3 months after the transplant

  4. Safety of the treatment with LIS1: Graft rejection

    Clinical safety parameters (4): Graft rejection (yes/no).

    Measured: 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).

    Measured: 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).

    Measured: 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).

    Measured: up to 3 months after the transplant

  8. Safety of the treatment with LIS1: CRP

    Laboratory parameters (1): C-Reactive Protein (CRP, mg/L).

    Measured: up to 3 months after the transplant

  9. Safety of the treatment with LIS1: LDH

    Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L).

    Measured: up to 3 months after the transplant

  10. Safety of the treatment with LIS1: aPTT

    Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds).

    Measured: 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).

    Measured: up to 3 months after the transplant

  12. Pharmacodynamics (depletion of T lymphocytes) of LIS1

    Absolute T lymphocyte counts (10^9/L).

    Measured: up to 3 months after the transplant

Secondary outcomes (7)

  1. Pharmacokinetics of LIS1 (1): swine IgG

    Serum concentration of swine IgG

    Measured: up to 3 months after the transplant

  2. Pharmacodynamics of LIS1 (2): cytokines

    Cytokine concentration (IL6, TNFα) (ng/mL).

    Measured: up to 3 months after the transplant

  3. Biology of LIS1 (1): electrolytes plasma concentration

    Plasma biochemistry: electrolytes (Na+, K+, Cl-, Ca++, Mg++, bicarbonates plasma concentrations mmol/L)

    Measured: up to 3 months after the transplant

  4. Biology of LIS1 (2): urea and creatinine

    Plasma biochemistry: urea and creatinine plasma concentration (mmol/L)

    Measured: up to 3 months after the transplant

  5. Biology of LIS1 (3): total plasma proteins

    Plasma biochemistry: Total protein plasma concentration (g/L)

    Measured: up to 3 months after the transplant

  6. 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)

    Measured: up to 3 months after the transplant

  7. Immunogenicity of LIS1

    Detection of antidrug antibodies in serum

    Measured: up to 3 months after the transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2020
  2. Study start26 Nov 2019
  3. Primary completion28 Mar 2022
  4. Study completion28 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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.
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04431219
Sponsor's protocol ID
XT-1901
Status last verified
Aug 2022
First submitted
28 May 2020
Last updated
17 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Viklicky O, Slatinska J, Janousek L, Rousse J, Royer PJ, Toutain PL, Cozzi E, Galli C, Evanno G, Duvaux O, Bach JM, Soulillou JP, Giral M, Vanhove B, Blancho G. First-in-human Study With LIS1, a Next-generation Porcine Low Immunogenicity Antilymphocyte Immunoglobulin in Kidney Transplantation. Transplantation. 2024 Jul 1;108(7):e139-e147. doi: 10.1097/TP.0000000000004967. Epub 2024 Feb 29.

    PubMed 38421879

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LIS1 in people with Kidney Transplant, run by Xenothera SAS at 1 site in Czechia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of the treatment with LIS1: Blood pressure (time frame: up to 3 months after the transplant). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04431219, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2022.

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