A Multicentre, Open-Label, Single Ascending Dose, Dose-Ranging, Phase I/IIa Study to Evaluate the Safety and Tolerability of an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (TX200-TR101) in Living Donor Renal Transplant Recipients (STEADFAST)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sangamo Therapeutics France

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

17 Mar 2021 → 17 Oct 2025

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sangamo Therapeutics France SAS

External identifiers

EU CT number

2024-512579-11-00

EudraCT number

2019-001730-34

WHO UTN

U1111-1305-2706

ClinicalTrials.gov

NCT04817774

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response, Safety, Pharmacodynamic, Efficacy

To evaluate the short-term safety and tolerability of TX200-TR101 from the day of TX200-TR101 infusion within 28 days post TX200-TR101 infusion.

Secondary objectives 5

1. 1 To evaluate the effect of TX200-TR101 on acute graft-related outcomes from the day of TX200-TR101 infusion through to Week 84 in terms of BCAR (including type severity and timing).
2. 2 To evaluate the effect of TX200-TR101 on long-term safety outcomes from the day of TX200-TR101 infusion through to Week 84 in terms of TEAEs.
3. 3 To evaluate the reduction of immunosuppression over time through to Week 84.
4. 4 To evaluate TX200-TR101 localization in the graft at Week 16.
5. 5 To evaluate the effect of TX200-TR101 on chronic graft-related outcomes from the day of TX200-TR101 infusion through to Week 84.

Conditions and MedDRA coding

Prophylaxis against renal transplant rejection

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Paul-Ehrlich-Institut, Federal Agency For Medicines And Health Products, Medicines Evaluation Board

Plan to share IPD

No

IPD plan description

Undecided

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Willing and able to provide written informed consent (IC) in accordance with local regulations and governing Independent Ethics Committee (IEC) or Institutional Review Board (IRB) requirements prior to any procedure or evaluation performed specifically for the sole purpose of the study.
2. 2. Male or female aged between 18 and 70 (inclusive) years.
3. 3. Have diagnosis of ESRD and currently waiting for a new kidney from an identified live donor.
4. 4. Subjects who will be single organ recipients (kidney).
5. 5. Normal or non-clinically significant abnormality in the electrocardiogram (ECG), at investigator’s discretion.
6. 6. Women who are of childbearing potential must have a negative serum pregnancy test at screening and before transplantation.
7. 7. Able and willing to use a highly effective method of contraception from the signing of the informed consent through the last study visit, for male and female subjects with reproductive potential.

Exclusion criteria 8

1. 1.HLA identical to the prospective organ donor.
2. 2.Subjects with prior organ transplant.
3. 3.Positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
4. 4.Subjects with panel-reactive antibody (PRA) greater than 20% within 6 months prior to enrolment.
5. 5. Subjects with current or recent (within 6 months) donor-specific antibodies.
6. 6. Subjects with underlying renal disease with a high risk of disease reoccurrence in the transplanted kidney including primary focal segmental glomerulosclerosis, types I or II membranoproliferative glomerulonephritis, C3 glomerulopathy, or haemolytic-uraemic syndrome (HUS), including atypical HUS.
7. 7. Concomitant clinically active local or systemic infection.
8. 8. Clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, haematologic, gastrointestinal, hepatic, neurological, malignancy or infectious diseases) or laboratory abnormality (except ESRD) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and grade of TEAEs, including SAEs, within 28 days post TX200-TR101 infusion.

Secondary endpoints 5

1. 1. From the day of TX200-TR101 infusion through to Week 84 - Incidence of BCAR according to the Banff criteria, Time to first BCAR episode, Type and severity of any BCAR episodes according to the Banff criteria.
2. 2. From the day of TX200-TR101 infusion through to Week 84: Incidence and grade of TEAEs, including SAEs. Incidence of opportunistic infections, specifically BKV, EBV and CMV reactivation. Incidence of neoplasia.
3. 3. Proportion of subjects who are receiving tacrolimus monotherapy at Week 84., Cumulative dose of immunosuppression, including but not limited to MPA/MMF and tacrolimus through to Week 84.
4. 4. Presence of CD4 positive cells that are also positive for HLA-A2 CAR RNA transcripts in the renal transplant biopsy at Week 16 (4 weeks following TX200-TR101 infusion).
5. 5. From the day of TX200-TR101 infusion through to Week 84. Incidence and severity of chronic graft dysfunction, as measured by eGFR. Incidence and severity of chronic graft dysfunction, as measured by the Banff criteria for chronic rejection including the Banff lesion score i-IFTA. Incidence of graft loss due to rejection. Incidence and (semi-quantitative) intensity of de novo DSA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sangamo Therapeutics France

Sponsor organisation

Sangamo Therapeutics France

Address

Les Cardoulines Ht1 Allee De La Nertiere, Sophia Antipolis Sophia Antipolis

City

Valbonne

Postcode

06560

Country

France

Scientific contact point

Organisation

Sangamo Therapeutics France

Contact name

Sangamo Patient Advocacy

Public contact point

Organisation

Sangamo Therapeutics France

Contact name

Sangamo Patient Advocacy

Third parties 17

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications