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

Study Overview
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Brief Summary
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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.

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

Conditions
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Ulcerative Colitis (UC)

Intervention / Treatment
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* Device: TLA Gut™


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low dose (1.8 L)<br>Patients in this arm will be treated with one column (Leukapheresis) and 1.8 L blood will be filtered. | Device: TLA Gut™<br>* 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.<br>|
| Experimental: high dose (3.6 L)<br>Patients in this arm will be treated with Two column (Leukapheresis) and 3.6 L blood will be filtered. | Device: TLA Gut™<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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