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

Primary Purpose

Ulcerative Colitis (UC)

Status

Recruiting

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

TLA Gut™

About this trial

This is an interventional treatment trial for Ulcerative Colitis (UC)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Ersta Sjukhus, MedicinklinikenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

low dose (1.8 L)

high dose (3.6 L)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Evaluate whether the intervention of TLA Gut™ reduces Human Leukocyte Antigen DR isotype (HLADRhi)

Mean percentage change in HLA-DRhi expressing monocytes

Secondary Outcome Measures

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

Mean change in HLA-DRhi expressing monocytes

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

Mean change and mean percentage change in Mayo Score Index

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

Mean percentage change in faecal calprotectin levels

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

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

Proportion of patients in each dosing group classified as responders

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

Mean change and mean percentage change in Mayo Endoscopic Sub-Score Index

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

Full Information

NCT ID

NCT04550130

First Posted

April 9, 2020

Last Updated

November 7, 2022

Sponsor

TLA, Targeted Immunotherapies AB

1. Study Identification

Unique Protocol Identification Number

NCT04550130

Brief Title

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

Official Title

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

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 2022 (Anticipated)

Primary Completion Date

April 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

TLA, Targeted Immunotherapies AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ulcerative Colitis (UC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

low dose (1.8 L)

Arm Type

Experimental

Arm Description

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

Arm Title

high dose (3.6 L)

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

TLA Gut™

Intervention Description

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.

Primary Outcome Measure Information:

Title

Evaluate whether the intervention of TLA Gut™ reduces Human Leukocyte Antigen DR isotype (HLADRhi)

Description

Mean percentage change in HLA-DRhi expressing monocytes

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Mean change in HLA-DRhi expressing monocytes

Time Frame

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

Title

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

Description

Mean change and mean percentage change in Mayo Score Index

Time Frame

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

Title

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

Description

Mean percentage change in faecal calprotectin levels

Time Frame

baseline, during treatment (at week 6), immediately after treatment completion

Title

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

Description

Proportion of patients in each dosing group achieving laboratory remission, clinical remission or both laboratory and clinical remission

Time Frame

immediately after treatment completion

Title

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

Description

Proportion of patients in each dosing group classified as responders

Time Frame

immediately after treatment completion

Title

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

Description

Mean change and mean percentage change in Mayo Endoscopic Sub-Score Index

Time Frame

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

Title

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

Description

Mean change and mean percentage change in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Ersta Sjukhus, Medicinkliniken

City

Stockholm

ZIP/Postal Code

116 91

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

TLA

Phone

TLA

purchasing@ithgroup.se

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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