ICH GCP - EU Clinical trials Registry - 2022-002440-40 (NL)

Kliniska prövningar Nct sida

Summary
EudraCT Number:	2022-002440-40
Sponsor's Protocol Code Number:	TX200-KT03
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2022-002440-40

A.3

Full title of the trial

Long-Term Follow-Up of Patients who have received an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (CAR- Treg therapy, TX200-TR101) in a prior clinical study.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Long-Term Follow-Up of Patients who have received an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (CAR- Treg therapy, TX200-TR101) in a prior clinical study.

A.3.2

Name or abbreviated title of the trial where available

Long-Term Follow-Up of TX200-TR101 (STEADFAST Long Term)

A.4.1

Sponsor's protocol code number

TX200-KT03

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sangamo Therapeutics France SAS
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sangamo Therapeutics France SAS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sangamo Therapeutics France SAS
B.5.2	Functional name of contact point	TX200-KT03 Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Les Cardoulines HT1, Allée de la Nertière
B.5.3.2	Town/ city	Valbonne
B.5.3.3	Post code	06560
B.5.3.4	Country	France
B.5.6	E-mail	smb-tx200-regulatory@sangamo.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/22/2647 EMA/0D/0000078610
D.3 Description of the IMP
D.3.1	Product name	Autologous HLA-A2 Chimeric Antigen Receptor T regulatory cells
D.3.2	Product code	TX200-TR101
D.3.4	Pharmaceutical form	Dispersion for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet assigned
D.3.9.2	Current sponsor code	TX200-TR101
D.3.9.3	Other descriptive name	Autologous naive regulatory T cells transduced with a lentiviral vector encoding for a chimeric antigen receptor to recognise the HLA-A*02 antigen
D.3.9.4	EV Substance Code	SUB201165
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25E+06
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of immune mediated allograft rejection in patients with end-stage renal disease (ESRD) who are tissue typed as HLA-A*02 negative
and have received a kidney transplant from an HLA-A*02 positive living donor.

E.1.1.1

Medical condition in easily understood language

Prevention of kidney graft rejection in patients who have received a kidney transplant due to chronic renal insufficiency.

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10050436
E.1.2	Term	Prophylaxis against renal transplant rejection
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the long-term safety and tolerability of TX200-TR101 up to 15 years post-TX200-TR101 infusion/baseline.

E.2.2

Secondary objectives of the trial

To evaluate the effect of TX200-TR101 on long-term graft-related outcomes up to 15 years post-TX200-TR101 infusion/baseline.

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 and impact in the periphery up to 15 years post-TX200-TR101 infusion/baseline (if available).

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal exclusion criteria

None.

E.5 End points

E.5.1

Primary end point(s)

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).

E.5.1.1

Timepoint(s) of evaluation of this end point

From the day of TX200-TR101 infusion through to 15 years post-TX200-TR101 infusion/baseline

E.5.2

Secondary end point(s)

• 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).

• Number of in-patient days in hospital
• Incidence of any Adverse Events (AEs)considered related to TX200-TR101 according to the investigator
• Incidence of Adverse Events of Special Interest (AESI), including:
o Infections requiring medical intervention, where severity is Grade 2 or greater. Any infection that is suspected or confirmed
opportunistic in nature; new-onset diabetes mellitus (NODM), new or aggravation of hypertension, new malignancies, 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.

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®

Levels (absolute values) and changes from baseline (i.e. Pre- TX200-TR101 infusion/baseline) in biomarkers in blood relating to the presence of HLA-A2 CAR-Tregs

E.5.2.1

Timepoint(s) of evaluation of this end point

From the day of TX200-TR101 infusion through to 15 years post-TX200-TR101 infusion/baseline

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Long-Term Follow--Up study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Netherlands

Germany

Belgium

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-12-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-10

P. End of Trial
P.	End of Trial Status	Ongoing

Kliniska prövningar Nct sida

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner