Kidney TransplantationPRE-TREGNCT04661254
Treg Cell Therapy in Liver and Kidney Transplantation - Preclinical Validation of Batches of Treg Cells Amplified in Vitro
A study testing Lymphapheresis in people with Kidney Transplantation and Liver Transplantation, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
Kidney and liver transplantation requires a fine tuning of immune responses in order to achieve long term operational tolerance with immunosuppressants or immune modulators. Numerous experimental findings indicate that CD4+ FOXP3 expressing regulatory T (Treg) cells play a central role in the induction of tolerance to… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Transplantation, Liver Transplantation
- What is being tested?
- Lymphapheresis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesFrance
- Study dates
- 15 Apr 2023to 30 Apr 2024
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For liver transplant patients:
- Liver transplantation carried out for 1 to 3 months for alcoholic cirrhosis;
- Normal liver biological test;
- Normal hepatic morphological assessment;
- For kidney transplant patients:
- Renal transplantation carried out for 3 to 6 months for any disease requiring renal transplantation;
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- Normal renal biological assessment;
- Normal renal morphological assessment;
- DSA <1500 MFI at inclusion
- Common criteria:
- Age ≥ 18 years and ≤ 70 years
- GB ≥1500 / mm3
- Hemoglobin level> 10g / 100ml
- Platelets> 50,000 / μl
- Weight> 40Kg
- Informed and signed consent;
- Patient affiliated to a social security scheme
Who cannot join
- For liver transplant patients:
- Hepatocellular carcinoma or history of another cancer;
- For kidney transplant patients:
- Kidney cancer or a history of another cancer
- Common criteria:
- Active infectious diseases: positive serology for hepatitis A, B or C, HIV, HTLV, CMV and EBV;
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- Associated autoimmune disease, including type 1 diabetes;
- GB <1500 / mm3;
- Any contraindication to citrate and calcium gluconate.
- Pregnancy or lactating woman
- Patient under guardianship or curatorship
- Patient deprived of liberty or under administrative security measure
Trial locations and contacts
2 sites in 1 country.
France2 sites
Pitié Salpêtrière hospital
Paris, 75013
CONTI Filomena, MD, PhD, +33 1 84 82 74 21, filomena.conti@aphp.fr
Pitié Salpêtrière hospital
Paris, 75013
BARROU Benoit, MD, PhD, +33 1 42 17 71 62, benoit.barrrou@aphp.fr
About this study
Kidney and liver transplantation requires a fine tuning of immune responses in order to achieve long term operational tolerance with immunosuppressants or immune modulators. Numerous experimental findings indicate that CD4+ FOXP3 expressing regulatory T (Treg) cells play a central role in the induction of tolerance to the grafts indicating that the use of Treg cells may be an innovative therapeutic strategy in kidney transplantation that would enable the diminution of immunosuppressive drugs or even their discontinuation, thus decreasing their risk of adverse events.
As human Treg cells represent less than 10% of CD4+ T cells, and because it has been shown in mice that a dose of 2*104 polyclonal Tregs/g was necessary to induce tolerance in animal models of solid organ transplantation, it is mandatory to expand human Treg cells ex vivo, after isolating them from peripheral blood. The investigators previously defined a protocol for Treg cell isolation and expansion in clinical grade conditions (cGMP) that enabled us to obtain the expected number of expanded cells maintaining high levels of FOXP3 (3).
Read more
The investigators therefore hypothesize in humans, as it has been already shown in mice, that the infusion of autologous expanded polyclonal Treg cells would lead to the obtaining of operational tolerance in kidney and liver graft in association with classical immunosuppressants and an expectable diminution of those.
To this end, it is necessary to have pre-clinical batches of expanded Treg cells validated by the National Agency for Medicines and Health Products Safety validate (ANSM). The investigators therefore plan to have 4 batches from 2 liver transplant patients and 2 kidney transplant patients validated.
- Conditions
- Kidney Transplantation, Liver Transplantation
- Being tested
- Lymphapheresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LymphapheresisOther
- From the blood product of lymphapheresis: Autologous naïve regulatory CD45RA+CD4+CD25+FoxP3+ T lymphocytes (Tregs) selected and amplified ex vivo; obtained by selection and sorting of CD4+CD25 +CD127lowCD45RA+ cells, derived from lymphapheresis and amplified ex vivo for 10 +/- 1 days, under cGMP condition in the presence of IL2 and Rapamycin
| Study group | Role | What they receive |
|---|---|---|
| Lymphapheresis | Other | Blood is drawn from one of the patient's two arms and passes through a separation circuit. After removing the white blood cells, it is reinjected into the other arm. Receives: Other: Lymphapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Validate 4 preclinical batches of Treg cells from 2 liver transplant patients and 2 kidney transplant patients
Treg cells produced according to the expansion protocol defined by verifying the compliance of the batches according to the requirements of the guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Product) by respecting the validation and batch release criteria defined in this protocol.
Measured: At day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start15 Apr 2023 (estimated)
- Primary completion30 Apr 2024 (estimated)
- Study completion30 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MIYARA Makoto, MD, PhD, Principal investigator, AP-HP - Pitié Salpêtrière hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04661254
- Sponsor's protocol ID
- APHP200733
- Other IDs
- 2020-A01871-38
- Acronym
- PRE-TREG
- Status last verified
- Mar 2023
- First submitted
- 3 Dec 2020
- Last updated
- 28 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treg Cell Therapy in Liver and Kidney Transplantation - Preclinical Validation of Batches of Treg Cells Amplified in Vitro
- ClinicalTrials.gov ID
- NCT04661254
- Acronym / sponsor ID
- PRE-TREG / APHP200733
- Conditions
- Kidney Transplantation, Liver Transplantation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 15 Apr 2023 (estimated)
- Primary completion
- 30 Apr 2024 (estimated)
- Study completion
- 30 Apr 2024 (estimated)
- First posted
- 10 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Kidney and liver transplantation requires a fine tuning of immune responses in order to achieve long term operational tolerance with immunosuppressants or immune modulators. Numerous experimental findings indicate that CD4+ FOXP3 expressing regulatory T (Treg) cells play a central role in the induction of tolerance to the grafts indicating that the use of Treg cells may be an innovative therapeutic strategy in kidney transplantation that would enable the diminution of immunosuppressive drugs or even their discontinuation, thus decreasing their risk of adverse events.
As human Treg cells represent less than 10% of CD4+ T cells, and because it has been shown in mice that a dose of 2*104 polyclonal Tregs/g was necessary to induce tolerance in animal models of solid organ transplantation, it is mandatory to expand human Treg cells ex vivo, after isolating them from peripheral blood. The investigators previously defined a protocol for Treg cell isolation and expansion in clinical grade conditions (cGMP) that enabled us to obtain the expected number of expanded cells maintaining high levels of FOXP3 (3).
The investigators therefore hypothesize in humans, as it has been already shown in mice, that the infusion of autologous expanded polyclonal Treg cells would lead to the obtaining of operational tolerance in kidney and liver graft in association with classical immunosuppressants and an expectable diminution of those.
To this end, it is necessary to have pre-clinical batches of expanded Treg cells validated by the National Agency for Medicines and Health Products Safety validate (ANSM). The investigators therefore plan to have 4 batches from 2 liver transplant patients and 2 kidney transplant patients validated.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lymphapheresis | Other | Other: LymphapheresisBlood is drawn from one of the patient's two arms and passes through a separation circuit. After removing the white blood cells, it is reinjected into the other arm. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Liver transplantation carried out for 1 to 3 months for alcoholic cirrhosis;
- Normal liver biological test;
- Normal hepatic morphological assessment;
- Renal transplantation carried out for 3 to 6 months for any disease requiring renal transplantation;
- Normal renal biological assessment;
Key exclusion criteria (12 listed)
- Hepatocellular carcinoma or history of another cancer;
- Kidney cancer or a history of another cancer
- Active infectious diseases: positive serology for hepatitis A, B or C, HIV, HTLV, CMV and EBV;
- Associated autoimmune disease, including type 1 diabetes;
- GB <1500 / mm3;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lymphapheresis- From the blood product of lymphapheresis: Autologous naïve regulatory CD45RA+CD4+CD25+FoxP3+ T lymphocytes (Tregs) selected and amplified ex vivo; obtained by selection and sorting of CD4+CD25 +CD127lowCD45RA+ cells, derived from lymphapheresis and amplified ex vivo for 10 +/- 1 days, under cGMP condition in the presence of IL2 and Rapamycin | Other | Lymphapheresis |
Primary outcome
Validate 4 preclinical batches of Treg cells from 2 liver transplant patients and 2 kidney transplant patients
Time frame: At day 10
Treg cells produced according to the expansion protocol defined by verifying the compliance of the batches according to the requirements of the guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Product) by respecting the validation and batch release criteria defined in this protocol.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MIYARA Makoto, MD, PhD principal investigator
AP-HP - Pitié Salpêtrière hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lymphapheresis in people with Kidney Transplantation and Liver Transplantation, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
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 17 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MIYARA Makoto, MD, PhD (+33 1 42 17 84 91, makoto.miyara@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Validate 4 preclinical batches of Treg cells from 2 liver transplant patients and 2 kidney transplant patients (time frame: At day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Mar 2023.