Dose-Evaluation Study of the Efficacy and Safety of TLA Gut™ Leukapheresis Treatment in Patients With Ulcerative Colitis

Overview

An open-label, randomised, multi-centre, dose evaluation study of the efficacy and safety of TLA Gut™ leukapheresis treatment in patients with UC. The aim of this trial is to evaluate the efficacy and safety of two different TLA Gut™ dose regimens in patients with acute exacerbation of UC. Enrolled patients will participate in a 6-week treatment phase and a 20- week follow-up phase. The treatment phase consists of two periods; 2 weeks in which patients will undergo two treatment sessions per week, followed by 4 weeks of a single treatment session per week. The follow-up phase consists of 2 visits, one visit at week 7 and the last visit at week 26. Telephone visits will be conducted between these visits. In all a patient will undergo 8 treatment visits and 2 follow-up visits. Only patients not having experienced an earlier recurrence will participate in the follow-up phase.

Full Title of Study: “An Open-label, Randomised, Multi-centre, Dose-Evaluation Study of the Efficacy and Safety of TLA Gut™ Leukapheresis Treatment in Patients With Ulcerative Colitis”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2020

Interventions

  • Device: TLA Gut™
    • The medical device to be investigated is named Tailored Leukapheresis (TLA) Gut™. The device comprises a column that has been designed for extracorporeal leukapheresis to specifically remove chemokine (C-C motif) receptor 9 (CCR9) expressing immunological cell populations including human leukocyte antigen DR isotype (HLA-DRhi ) monocytes from the circulation. This is achieved by integrating a strong affinity binding between the gut homing cell receptor, CCR9, and its cognate ligand, thymus-expressed chemokine (TECK) or chemokine ligand 25 (CCL25). Those blood cells that express CCR9 will bind to presented Biotinylated thymus-engineered chemokine (bTECK) on the matrix by a strong receptor ligand interaction, remaining bound to the matrix. Blood cells that do not express the receptor pass through the column unchanged and are returned to the patient.

Arms, Groups and Cohorts

  • Experimental: low dose (1.8 L)
    • Patients in this arm will be treated with one column (Leukapheresis) and 1.8 L blood will be filtered.
  • Experimental: high dose (3.6 L)
    • Patients in this arm will be treated with Two column (Leukapheresis) and 3.6 L blood will be filtered.

Clinical Trial Outcome Measures

Primary Measures

  • Evaluate whether the intervention of TLA Gut™ reduces Human Leukocyte Antigen DR isotype (HLADRhi)
    • Time Frame: baseline, during treatment (after 4 treatment sessions at week 2)
    • Mean percentage change in HLA-DRhi expressing monocytes

Secondary Measures

  • Evaluate the effect of intervention of TLA Gut™ on clinical, histopathology and laboratory criteria and variables
    • Time Frame: baseline, during treatment (after 4 treatment sessions at week 2)
    • Mean change in HLA-DRhi expressing monocytes
  • Evaluate the effect of intervention of TLA Gut™ on clinical variables
    • Time Frame: baseline, after 4 treatment sessions at week 2 , immediately after treatment completion
    • Mean change and mean percentage change in Mayo Score Index
  • Evaluate the effect of intervention of TLA Gut™ on laboratory criteria
    • Time Frame: baseline, during treatment (at week 6), immediately after treatment completion
    • Mean percentage change in faecal calprotectin levels
  • Evaluate the effect of intervention of TLA Gut™ on clinical, histopathology and laboratory criteria and variables
    • Time Frame: immediately after treatment completion
    • Proportion of patients in each dosing group achieving laboratory remission, clinical remission or both laboratory and clinical remission
  • Evaluate the effect of intervention of TLA Gut™ on clinical variables
    • Time Frame: immediately after treatment completion
    • Proportion of patients in each dosing group classified as responders
  • Evaluate the effect of intervention of TLA Gut™ on clinical variables
    • Time Frame: baseline, after 4 treatment sessions at week 2 , immediately after treatment completion
    • Mean change and mean percentage change in Mayo Endoscopic Sub-Score Index
  • Evaluate the effect of intervention of TLA Gut™ on clinical variables
    • Time Frame: baseline, after 4 treatment sessions at week 2 , immediately after treatment completion
    • Mean change and mean percentage change in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score

Participating in This Clinical Trial

Inclusion Criteria

Female or male patients 18 to 80 years of age

  • Active UC without Ileorectal anastomosis (IRA)
  • Active UC is defined as:
  • Total Mayo score of ≥ 6 to 11 points
  • Flexible rectosigmoidoscopy findings of 2 or 3 (0 inactive disease, 1; mild disease, 2; moderate disease or 3; severe disease)
  • Minimum extension of inflammation 10 cm from anus.
  • Active disease with no medical treatment OR Active disease despite receiving concomitant therapy with one or more of the following agents:
  • ≤20 mg prednisolone daily. Stable dose ≥1 week prior to the start of the investigation.
  • 5-Aminosalicylate (5-ASA) agents for ≥4 weeks and stable dose for ≥2 weeks (local or systemic administration)
  • Rectal administration of corticosteroids in a stable dose for ≥2 weeks
  • Azathioprine or 6-mercaptopurine for ≥8 weeks or stable dose ≥2 weeks
  • No anti-tumour necrosis factor (TNF) treatment (Adalimumab, Infliximab, Golimumab, Certolizumab), anti-integrin-treatment (vedolizumab), Interleukin (IL)-12/23 inhibitor (Ustekinumab) or Janus Kinase (JAK) treatment (Tofacitinib) during the last 4 weeks prior to entering the study
  • Patients with peripheral veins suitable for extracorporeal treatment – must be examined by the treating apheresis specialist
  • Willing and able to give written informed consent

Exclusion Criteria

Involvement in any investigational drug or device trial within 30 days prior to this investigation

  • Patients with peripheral veins not suitable for extracorporeal treatment
  • Fever, defined as a temperature of >38,5 Celsius degrees (ºC), at the Screening Visit
  • Heart failure
  • Coronary artery disease
  • Cardiomyopathy
  • Valvular heart disease
  • Cardiac arrythmia class IV
  • Underweight person (BMI < 19)
  • Hypotension (< 90/55 mmHG)
  • Hypoproteinemia
  • Evidence of toxic megacolon
  • History of hypersensitivity to heparin
  • Heparin-induced thrombocytopenia
  • History of cerebrovascular incident
  • Known clinically significant bleeding disorder
  • Colectomy planned within 6 months
  • Concomitant anticoagulant therapy
  • History of hypercoagulable disorders
  • Severe anaemia or Leukopenia
  • Patients with active viral hepatitis and/or human immunodeficiency virus (HIV) infections
  • A positive urine pregnancy test at the screening visit
  • Patients that are nursing Local intestinal treatments with suppositories, enemas, creams, ointments or foams during the last 2 weeks
  • Current daily smoking habits
  • Patients unwilling to meet the requirements of the clinical investigational plan
  • Other medical or social reasons for exclusion at the discretion of the investigator

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • TLA, Targeted Immunotherapies AB
  • Provider of Information About this Clinical Study
    • Sponsor

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