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

NCT04550130 | Unknown

• 1 other identifier: TLA002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis (UC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Evaluate the effect of intervention of TLA Gut™ on clinical, histopathology and laboratory criteria and variables

  baseline, during treatment (after 4 treatment sessions at week 2)

• Evaluate the effect of intervention of TLA Gut™ on clinical variables

  baseline, after 4 treatment sessions at week 2 , immediately after treatment completion

• Evaluate the effect of intervention of TLA Gut™ on laboratory criteria

  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

  immediately after treatment completion

• Evaluate the effect of intervention of TLA Gut™ on clinical variables

  immediately after treatment completion

Study Arms (2)

low dose (1.8 L)

EXPERIMENTAL

Patients in this arm will be treated with one column (Leukapheresis) and 1.8 L blood will be filtered.

Device: TLA Gut™

high dose (3.6 L)

EXPERIMENTAL

Patients in this arm will be treated with Two column (Leukapheresis) and 3.6 L blood will be filtered.

Device: TLA Gut™

Interventions

TLA Gut™ DEVICE

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.

high dose (3.6 L); low dose (1.8 L)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• TLA, Targeted Immunotherapies AB: lead

Study Sites (1)

Ersta Sjukhus, Medicinkliniken

Stockholm, 116 91, Sweden

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: September 16, 2020
• Study Start: December 1, 2022
• Primary Completion: April 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)