This study has been transitioned to CTIS with ID 2024-512580-31-00 check the CTIS register for the current data. PrimaryTo evaluate the long-term safety and tolerability of TX200-TR101 up to 15 years post-TX200-TR101 infusion/baseline.SecondaryTo…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
From the day of TX200-TR101 infusion through to 15 years post-TX200-TR101
infusion/baseline:
• Overall survival
• Incidence and grade of Serious Adverse Events (SAEs).
Secondary outcome
Secondary
From the day of TX200-TR101 infusion through to 15 years post-TX200-TR101
infusion/baseline:
• Incidence of immune-mediated rejection in terms of BCAR episodes according to
the Banff criteria (including type, severity and timing)
• Incidence of graft loss due to rejection
• Incidence and severity of chronic graft dysfunction, as measured by eGFR
• Incidence and (semi-quantitative) intensity of de novo donor-specific
anti-HLA antibodies (DSA).
Exploratory
From the day of TX200-TR101 infusion through to 15 years post-TX200-TR101
infusion/baseline:
• Number of in-patient days in hospital
• Incidence of any Adverse Events (AE) considered related to TX200-TR101
according to the investigator
• Incidence of Adverse Events of Special Interest (AESI), including
(irrespective of grade):
o Any infection requiring medical intervention; any infection that is suspected
or confirmed opportunistic in nature; new-onset diabetes mellitus (NODM), new
incidence or exacerbation of a pre-existing neurological disorder; new
incidence or exacerbation of a prior rheumatological or other autoimmune
disorder; new incidence of a haematological disorder; new incidence or
exacerbation of hypertension, new malignancy, or new (up-to 8 years
post-infusion) dyslipidaemia requiring medical intervention
• Change in immunosuppression regimen to include:
o Target levels in blood for each immunosuppressant.
o Number and name of drugs given to achieve intended level of immunosuppression.
o Any incidence of rescue medication given to avoid potential imminent
rejection episode.
• Incidence of anti-drug antibodies against HLA-A2 CAR-Tregs.
• From the day of TX200-TR101 infusion/baseline through to 15 years
post-TX200-TR101 infusion/baseline, any of the following:
o Death, or;
o Incidence of immune-mediated rejection in terms of BCAR episodes according to
the Banff criteria (including type, severity and timing), or;
o Incidence of graft loss due to rejection, or;
o Incidence and severity of chronic graft dysfunction, as measured by eGFR
Absolute value and change from baseline in SF-36v2 from the day of TX200-TR101
infusion through to 15 years post-TX200-TR101 infusion/baseline.
Levels (absolute values) of HLA-A2 CAR-Tregs from the day of infusion through
to 5 years post-TX200-TR101 infusion/baseline.
Background summary
TX200-TR101, the study drug that subjects received in the previous study
(TX200-KT02) through infusion, is being investigated further in this study for
long-term effects and safety when it is administered to subjects with End-Stage
Renal Disease (ESRD). The study drug is made from their own cells, which are
modified and designed to modulate the immune system after they have received a
donated kidney. The safety and effects of the study drug are being compared by
utilising a control group of subjects.
Please refer to protocol section 1 (p17-19) for more information.
Study objective
This study has been transitioned to CTIS with ID 2024-512580-31-00 check the CTIS register for the current data.
Primary
To evaluate the long-term safety and tolerability of TX200-TR101 up to 15 years
post-TX200-TR101 infusion/baseline.
Secondary
To evaluate the effect of TX200-TR101 on long-term graft-related outcomes up to
15 years post-TX200-TR101 infusion/baseline.
Exploratory
To evaluate the effect of TX200-TR101 on long-term safety outcomes up to 15
years post-TX200-TR101 infusion/baseline.
To evaluate the composite efficacy profile of TX200-TR101 up to 15 years
post-TX200-TR101 infusion/baseline.
To evaluate quality of life over time up to 15 years post-TX200-TR101
infusion/baseline.
To evaluate the long-term persistence of CAR-Tregs up to 5 years
post-TX200-TR101 infusion/baseline (if available).
Study design
Subjects will be invited to enrol in this LTFU study after they have either
completed the week 84 visit or have withdrawn from the Phase I/IIa study
(TX200-KT02). Subjects will be invited to read and sign the informed consent.
Transplant recipients who were administered TX200 TR101 in the TX200-KT02 study
will then proceed to have an additional 13.5 years of follow-up after
completion of the end of the TX200-KT02 study with administration of
TX200-TR101. Since these subjects will have completed the 1.5 years of
follow-up post-dosing with TX200 TR101 in the TX200-KT02 study, this LTFU will
thus enable the subjects to have a total of 15 years of observation
post-treatment with TX200-TR101.
Control transplant recipients will undergo the same amount of follow up, which
will equate to approximately 13.75 years of follow-up post-end-of-study
(control transplant recipients were not administered TX200-TR101 in the
TX200-KT02 study).
Subjects will undergo a combination of study visits and phone calls/Home Health
visits to gather information on their overall health, including information on
any SAEs, any new or change in existing concomitant medications (excluding
over-the-counter medications and any vaccinations), any hospitalisations
(including for rejection episodes, new or worsening comorbidities, or for any
other reason), and information on any new diagnoses or any other events of
relevance (e.g., pregnancy). Information on AESI (including infections
requiring medical intervention, where severity is Grade 2 or greater; any
infection that is suspected or confirmed opportunistic in nature, NODM, new or
aggravation of hypertension, new malignancies or new (up-to 8 years)
dyslipidemia requiring medical intervention) as well as any AEs considered
related to the TX200-TR101 according to the investigator will also be
collected.
Subjects will be asked during informed consent whether they give permission for
the study doctor to approach the subject*s treating physician (if different)
for more information on any health events, where applicable. Subjects will also
be asked during informed consent whether, in case any type of biopsy has been
obtained (e.g. for suspected malignancy and/or other reason, regardless of
relationship to renal disease), they give permission for a copy of the
histopathological assessment report to be shared with the study doctor, where
applicable.
Study visits are to be combined with standard of care visits where possible, to
minimise the burden on the subjects of additional in-clinic visits.
A subject is considered to have completed the study if he/she has completed the
end of study visit at Year 15 post-dosing with TX200-TR101/baseline. A
premature discontinuation will occur if a subject who signs the Informed
Consent Form (ICF) and is enrolled in the study ceases participation in the
study, regardless of circumstances, before the completion of the Year 15
protocol-defined study procedures. Subjects who discontinue from the study
prematurely, or are withdrawn from the study for any reason, will be asked to
return to the study site for an early termination visit.
In case of death of any TX200-TR101 subject, attempts should be made by the
investigator to collect renal allograft biopsy material for histopathological
analysis to understand the health of the kidney at the time of the subject*s
death. In addition, the investigator should attempt to obtain a report of
findings from any autopsy performed.
Study burden and risks
Since there will be no study-related treatment in this long-term follow-up
study, there are no new potential risks introduced by participating in this
study. There is a general minimal risk associated with conducting blood sample
collection/blood draws.
The burden for subjects is minimal during their participation in this LTFU
study. Their study visits and procedures are combined with SoC visits and
procedures as much as possible. What we learn during the LTFU can help
developing treatments for post-transplant care and/or (ESRD related) renal
transplants.
Allée de la Nertière, Les Cardoulines HT1 HT1
Valbonne 06560
FR
Allée de la Nertière, Les Cardoulines HT1 HT1
Valbonne 06560
FR
Listed location countries
Age
Inclusion criteria
1. Subjects who enrolled in the Phase I/IIa study TX200-KT02, received a
transplanted kidney and have either completed or withdrawn from that study.
2. Willing and able to provide written informed consent (IC) in accordance with
local regulations and governing Independent Ethics Committee
(IEC)/Institutional Review Board (IRB) requirements prior to any procedure or
evaluation performed specifically for the sole purpose of the study.
Exclusion criteria
1. Subjects/persons committed to an institution following an administrative or
judicial order.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512580-31-00 |
| EudraCT | EUCTR2022-002440-40-NL |
| CCMO | NL82794.000.22 |