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Autologous Ex Vivo Expanded Regulatory T Cells in Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT04691232
Recruitment Status : Recruiting
First Posted : December 31, 2020
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

Brief Summary:

Together with Crohn's disease (CD), ulcerative colitis (UC) is one of the major forms of inflammatory bowel diseases (IBD).Currently, no causative therapy is available, since the pathophysiology of this disease is incompletely understood (1-3) and clinical practice demonstrates that current therapies induce remission in subgroups of patients only. Scientific evidence suggests that colitogenic immune responses can be controlled by increasing the number of circulating regulatory T cells (Treg) (4). The production of large numbers of autologous Treg is possible by isolation of CD25+ cells from the whole blood of a patient and subsequent ex vivo expansion in the presence of the immunomodulatory drug rapamycin, Interleukin-2 (IL-2) and CD3/CD28 expander beads (5).

ER-TREG 01 is a single-center, open-label, fast-track phase I dose-escalation study designed to assess the safety profile and maximal tolerated dose (MTD) of a single infusion of ex vivo expanded autologous Treg in patients with active ulcerative colitis.


Condition or disease Intervention/treatment Phase
Ulcerative Colitis Autoimmune Diseases Biological: Regulatory T cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open-label, Fast-track Dose-escalation Clinical Trial Exploring the Safety and the Tolerability of Autologous ex Vivo Expanded Regulatory T Cells in Adults With Ulcerative Colitis
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : August 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Regulatory T cells
Intravenous infusion of a single dose of 0.5x10e6, 1x10e6, 2x10e6, 5x10e6 or 10x10e6 Treg/kg body weight
Biological: Regulatory T cells
Autologous, ex vivo expanded, regulatory T cells




Primary Outcome Measures :
  1. Dose-finding [ Time Frame: Visit 5 (4 weeks after adoptive Treg transfer) ]
    To define the maximum tolerable dose (MTD) of one single infusion of autologous ex vivo expanded regulatory T cells in patients with ulcerative colitis


Secondary Outcome Measures :
  1. Assessment of safety of one single Infusion of regulatory T cells [ Time Frame: Visit 5 (4 weeks after adoptive Treg transfer) ]
    To define the number of patients with treatment-related adverse events as assessed by CTCAE v. 5.0



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Ages Eligible for Study:   18 Years to 18 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have an established diagnosis of UC, with minimum time from diagnosis of ≥3 months
  • Patients must suffer from moderate to severe disease activity (disease should extend 15 cm or more above the anal verge) determined by a modified Mayo score (excluding the friability at grade 1 for the endoscopic sub score) of 6 to 12 with an endoscopic subscore ≥ 2 and no other individual subscore < 1.
  • Patients must have a WHO performance status of 0, 1 or 2 and must be in stable medical condition.
  • Patients must be between 18 and 75 years old and must be able and willing to give informed consent.
  • Women of child-bearing age must have a negative pregnancy test at enrollment in the study, must be willing to undergo monthly pregnancy tests until at least 3 months after adoptive Treg transfer and must oblige to use effective contraception until at least 3 months after adoptive Treg transfer. A highly effective method of birth control is defined as one that results in a low failure rate (ie, less than 1 percent per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner. For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on the contraceptive should be addressed.
  • Male study patients, who are partners of women of child-bearing age must be willing to use effective contraception until at least 3 months after adoptive Treg transfer. A highly effective method of birth control is defined as one that results in a low failure rate (ie, less than 1 percent per year) when used consistently and correctly, such as sexual abstinence, or a vasectomy. The solely use of condoms is not considered as an effective method of birth control. Therefore, partners of child-bearing age from male study patients should be willing to use implants, injectables, combined oral contraceptives or intrauterine devices (IUDs) a highly effective method of birth control. Information regarding the product under evaluation and its potential effect on the contraceptive should be addressed.
  • Patients must be willing to undergo a leukapheresis.
  • Patients must be willing to get hospitalized for at least 24 hours following adoptive Treg transfer, and to cooperate for the whole period of the trial.
  • Patients have to be either in remission under the allowed concomitant therapy described under the last inclusion criterion; or patients have to have received all beneficial pharmacological treatment lines before enrolment in this clinical trial.
  • Accomplishment of a washout phase for biological therapy of at least 4 weeks or no detectable serum trough levels
  • Concomitant therapy with oral corticosteroids (prednisone or equivalent up to 20 mg/day, stable for 2 weeks at inclusion), budesonide (9 mg/day, stable for 8 weeks at inclusion), 5-ASA (stable for 2 weeks at inclusion) and azathioprine (stable for 8 weeks, initiated at least 3 months ago) is permitted. Concomitant oral corticosteroids can be reduced at the investigator's discretion from visit 5 onwards (e.g. 5 mg reduction per week).≤

Exclusion Criteria:

  • Any of the above mentioned inclusion criteria are not met.
  • Impaired hematological function (on repeated testing) as indicated by Leukocyte Count ≤ 2,500 /mm3, or Neutrophils ≤ 1,000 / mm3, or Lymphocytes ≤ 700 / mm3, or Platelets ≤ 75,000 / mm3, or Hemoglobin ≤ 9 g / dl22
  • Impaired hepatic or renal function as indicated by Serum creatinine ≥ 2.5 mg/100 ml, or Serum Bilirubin ≥ 2.0 mg/100 ml
  • Any other major serious illness [e.g. active systemic infections, immunodeficiency disease, clinically significant heart disease, respiratory disease, bleeding disorders, etc.] or a contraindication to leukapheresis.
  • Evidence for HIV-1, HIV -2, HTLV-1, TPHA, HBV, or HCV infection.
  • Patients who have spent a cumulative period of 1 year or more in the UK between the beginning of 1980 and the end of 1996
  • Patients who have a family history, which places them at risk of developing Creutzfeldt-Jacob disease
  • Patients who have received a corneal or dura mater graft, or who have been treated in the past with medicines made from human pituitary glands
  • Other active autoimmune diseases (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis).
  • Previous splenectomy or radiation therapy to the spleen.
  • Patients with organ allografts.
  • Concomitant treatment with chemotherapy, immunotherapy, any investigational drug and paramedical substances.
  • Existence or prior history of a malignant neoplasm.
  • Organic brain syndrome or significant psychiatric abnormality which would preclude participation in the full protocol and follow up.
  • Positive pregnancy test / Pregnancy or lactation. If pregnancy occurs during the course of the trial to female patients, the patient has to be excluded (not valid for partners of male patients treated).
  • Known hypersensitivities to human serum albumin and/or DMSO

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04691232


Contacts
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Contact: PD Dr. Caroline Bosch-Voskens, MD, PhD +49 9131 85 35000 caroline.bosch-voskens@uk-erlangen.de
Contact: Prof. Dr. med. Raja Atreya, MD +49 9131 85 35000 raja.atreya@uk-erlangen.de

Locations
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Germany
University of Erlangen-Nürnberg Medical School Recruiting
Erlangen, Bayern, Germany, 91054
Contact: PD Dr. Caroline Bosch-Voskens, MD, PhD    +49 9131 85 35000    caroline.bosch-voskens@uk-erlangen.de   
Contact: Prof. Dr. med. Raja Atreya, MD    +49 9131 85 35000    raja.atreya@uk-erlangen.de   
Principal Investigator: Prof. Dr. med. Markus Neurath, MD         
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
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Principal Investigator: Prof. Dr. med. Markus Neurath, MD University of Erlangen-Nürnberg Medical School
Publications:

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Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT04691232    
Other Study ID Numbers: ER-TREG 01
First Posted: December 31, 2020    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Erlangen-Nürnberg Medical School:
Ulcerative colitis
Regulatory T cells
Adoptive cell therapy
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Autoimmune Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Immune System Diseases