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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis (UC)
• Intervention / Treatment: Device: TLA Gut™

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 116 91
    • Recruiting
    • Ersta Sjukhus, Medicinkliniken
    • Contact: TLA; Phone Number: TLA; Email: purchasing@ithgroup.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
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.	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TLA, Targeted Immunotherapies AB

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: TLA002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No