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    Summary
    EudraCT Number:2019-001730-34
    Sponsor's Protocol Code Number:TX200-KT02
    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:2019-11-25
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2019-001730-34
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A 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
    A.4.1Sponsor's protocol code numberTX200-KT02
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSangamo Therapeutics France SAS
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSangamo Therapeutics France SAS
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSangamo Therapeutics France SAS
    B.5.2Functional name of contact pointTX200-KT02 Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressLes Cardoulines HT1, Allée de la Nertière
    B.5.3.2Town/ cityValbonne
    B.5.3.3Post code06560
    B.5.3.4CountryFrance
    B.5.6E-mailclinicaltrials@sangamo.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAutologous HLA-A2 Chimeric Antigen Receptor T regulatory cells
    D.3.2Product code TX200-TR101
    D.3.4Pharmaceutical form Dispersion for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot yet assigned
    D.3.9.2Current sponsor codeTX200-TR101-DS
    D.3.9.3Other descriptive nameAutologous HLA-A2 CAR T regulatory cells
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25E+06
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
    D.3.11.3.5.1CAT classification and reference numberGene therapy medicinal product, EMA/399634/2020
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another 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.1.1Medical 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.1.1.1Medical condition in easily understood language
    Prevention of kidney graft rejection in patients who have received a kidney transplant due to chronic renal insufficiency.
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10050436
    E.1.2Term Prophylaxis against renal transplant rejection
    E.1.2System Organ Class 100000004865
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    • 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 biopsy-confirmed acute rejection (BCAR).
    • 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 treatment emergent adverse events(TEAEs).
    • To evaluate the reduction of immunosuppression over time through to Week 84.
    • To evaluate TX200-TR101 localisation in the graft at Week 16.
    • To evaluate the effect of TX200-TR101 on chronic graft-related outcomes from the day of TX200-TR101 infusion through to Week 84.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria (All Transplant Recipients)
    1. 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.
    2. Male or female aged between 18 and 70 (inclusive) years.
    3. Have diagnosis of ESRD and currently waiting for a new kidney from an identified live donor.
    4. Subjects who will be single organ recipients (kidney).
    5. Normal or non-clinically significant abnormality in the electrocardiogram (ECG), at investigator’s discretion.
    6. Women who are of childbearing potential must have a negative serum pregnancy test at screening and before transplantation.
    7. Able and willing to use a highly effective method of contraception (see Appendix 2) from the signing of the informed consent through the last study visit, for male and female subjects with reproductive potential.

    Additional Inclusion Criteria (Transplant Recipients to be Administered TX200 TR101 Only)
    The following additional criteria must be met for transplant recipients to be administered TX200 TR101:
    1. HLA-A*02 negative typing (the kidney graft needs to be HLA A*02 positive).
    2. HLA-A*69 negative typing.
    3. Adequate venous access for leukapheresis, and no other contraindications for leukapheresis.

    Inclusion Criteria (All Transplant Donors)
    1. Willing and able to provide written IC in accordance with local regulations and governing IEC/IRB requirements prior to any procedure or evaluation performed specifically for the sole purpose of the study.
    2. Aged at least 18 years on the day of signing the IC form.
    3. ABO blood type compatible with the organ recipient.
    4. Negative serology for HIV and syphilis.
    5. Willing to provide personal and medical/biological data and samples for the study analysis.

    Additional Inclusion Criterion (Transplant Donors for Transplant Recipients to be Administered TX200-TR101 Only)
    The following additional inclusion criterion must be met for transplant donors for transplant recipients to be administered TX200 TR101:
    1. HLA-A*02 positive typing.
    E.4Principal exclusion criteria
    Exclusion Criteria (All Transplant Recipients)
    1. HLA identical to the prospective organ donor.
    2. Subjects with prior organ transplant.
    3. Known hypersensitivity to study medication ingredients or a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalisation.
    4. Known hypersensitivity or contraindications for anti-thymocyte globulin (ATG), tacrolimus or mycophenolic acid (MPA)/ mycophenolate mofetil (MMF).
    5. Positive serology for human immunodeficiency virus (HIV) or syphilis.
    6. Evidence of active or occult hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
    7. Subjects who are Epstein-Barr Virus (EBV) seronegative.
    8. Positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
    9. Subjects with panel-reactive antibody (PRA) >20% within 6 months prior to enrolment.
    10. Subjects with current, recent or historical donor-specific antibodies.
    11. Previous treatment with any desensitisation procedure (with or without intravenous immunoglobulin).
    12. Subjects with underlying renal disease with a high risk of disease reoccurrence in the transplanted kidney.
    13. Concomitant clinically active local or systemic infection.
    14. Use of any experimental medicinal product within 3 months or 5 half-lives prior to the screening visit, whichever is longer, and agreement to not take any experimental medicinal product throughout the trial.
    15. Subjects who are currently receiving systemic immunosuppressive agents (e.g., methotrexate, infliximab, adalimumab, corticosteroids) for other indications such as autoimmune diseases, or subjects with comorbidities for which treatment with such agents are likely during the study, with the following exception:
    • Subjects who are receiving or may require short-term and/or low dose (e.g., prednisone or prednisone equivalent < 5 mg daily) courses of corticosteroids are not precluded from enrolment, at the discretion of the investigator in consultation with the Sponsor’s Medical Monitor.
    16. Clinical evidence of significant unstable or poorly controlled acute or chronic diseases (e.g., cardiovascular, pulmonary, haematologic, gastrointestinal, hepatic, neurological, 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.
    • Subjects who, at the discretion of the investigator, are deemed at high risk of a renal thrombotic event.
    17. Subjects with current or previous history of clinically relevant central nervous system pathology (including but not limited to seizures, stroke, severe brain injury, cerebellar disease or CNS vasculitis).
    18. Current or previous history within the last 5 years of malignancy, with the following exceptions:
    • Subjects with any previous history of haematological malignancy are precluded from enrolment.
    • Subjects who have had non-melanoma skin cancer or cervical carcinoma in situ that have been successfully treated with no evidence of recurrence are not precluded from enrolment.
    19. Subjects whose life expectancy is severely limited by disease state other than renal disease.
    20. Subjects with a history of substance abuse (drug or alcohol) within the past 2 years or that is considered not compatible with adequate study follow-up, or psychiatric disorder or other condition that is not compatible with adequate study follow-up.
    21. Subjects with laboratory values that meet the following criteria are to be excluded (retesting once during the screening period is permitted at the investigator’s discretion):
    • Haemoglobin < 10 g/L
    • Platelets < 80 x 109/L
    • White blood cells (WBC) < 3 x 109/L
    • Aspartate transaminase (AST) and or alanine transaminase (ALT) ≥ 3 x upper limit of normal (ULN)
    • Total bilirubin ≥ 2 x ULN (except for subjects with Gilbert’s disease)
    22. Subjects who have received a live attenuated vaccine (LAV) within 30 days prior to their transplantation surgery.
    23. Subjects who are currently pregnant, planning pregnancy or breast feeding/lactating while enrolled in the study.
    24. Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study.

    Exclusion Criteria (All Transplant Donors)
    1. Exposure to investigational agents at the time of kidney donation or within 28 days or 5 half-lives whichever is longer, prior to the donation.
    2. Any form of substance abuse considered not compatible with adequate study follow-up, psychiatric disorder or other condition that in the opinion of investigator may compromise study participation.
    3. Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study.
    4. Evidence of active or occult HBV or active HCV infection.
    E.5 End points
    E.5.1Primary end point(s)
    Incidence and grade of TEAEs, including serious adverse events (SAEs) throughout 28 days post TX200-TR101 infusion.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The timepoint of evaluation of the primary endpoint is given in the section above ( E.5.1)
    E.5.2Secondary end point(s)
    From the day of TX200-TR101 infusion through to Week 84 unless otherwise specified below:
    •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.
    •Incidence and grade of TEAEs, including SAEs.
    •Incidence of opportunistic infections, specifically BK virus (BKV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation
    •Incidence of neoplasia.
    •Proportion of subjects who are receiving tacrolimus monotherapy at Week 84.
    •Cumulative dose of immunosuppression, including but not limited to mycophenolic acid (MPA)/mycophenolate mofetil (MMF) and tacrolimus through to Week 84.
    •Presence of CD4 RNA transcript positive cells that are also positive for HLA-A2 CAR RNA transcripts in the renal transplant biopsy at Week 16.
    •Incidence and severity of chronic graft dysfunction, as measured by estimated glomerular filtration rate (eGFR).
    •Incidence and severity of chronic graft dysfunction, as measured by the Banff criteria for chronic rejection including the Banff lesion score inflammation in area of interstitial fibrosis and tubular atrophy (i-IFTA).
    •Incidence of graft loss due to rejection.
    •Incidence and (semi-quantitative) intensity of de novo DSA.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The timepoint of evaluation of each secondary endpoint is given in the section above (E.5.2).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    France
    Germany
    Netherlands
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    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 (Last visit of the last subject)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 36
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 6
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 42
    F.4.2.2In the whole clinical trial 42
    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)
    Upon completion of this study, Transplant recipients, including control subjects, will be asked if they will participate in an additional, optional long-term follow-up study (within a separate protocol) after Week 84.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-11-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-03
    P. End of Trial
    P.End of Trial StatusOngoing
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