Dose-Evaluation Study of the Efficacy and Safety of TLA Gut™ Leukapheresis Treatment in Patients With Ulcerative Colitis
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| 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.
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| 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.
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Outcome Measures
Primary Outcome Measures
- Evaluate whether the intervention of TLA Gut™ reduces Human Leukocyte Antigen DR isotype (HLADRhi) [baseline, during treatment (after 4 treatment sessions at week 2)]
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 [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 [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 [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 [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 [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 [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 [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
Eligibility Criteria
Criteria
Inclusion Criteria:
Female or male patients 18 to 80 years of age
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Active UC without Ileorectal anastomosis (IRA)
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Active UC is defined as:
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Total Mayo score of ≥ 6 to 11 points
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Flexible rectosigmoidoscopy findings of 2 or 3 (0 inactive disease, 1; mild disease, 2; moderate disease or 3; severe disease)
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Minimum extension of inflammation 10 cm from anus.
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Active disease with no medical treatment OR Active disease despite receiving concomitant therapy with one or more of the following agents:
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≤20 mg prednisolone daily. Stable dose ≥1 week prior to the start of the investigation.
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5-Aminosalicylate (5-ASA) agents for ≥4 weeks and stable dose for ≥2 weeks (local or systemic administration)
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Rectal administration of corticosteroids in a stable dose for ≥2 weeks
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Azathioprine or 6-mercaptopurine for ≥8 weeks or stable dose ≥2 weeks
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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
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Patients with peripheral veins suitable for extracorporeal treatment - must be examined by the treating apheresis specialist
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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
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Patients with peripheral veins not suitable for extracorporeal treatment
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Fever, defined as a temperature of >38,5 Celsius degrees (ºC), at the Screening Visit
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Heart failure
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Coronary artery disease
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Cardiomyopathy
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Valvular heart disease
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Cardiac arrythmia class IV
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Underweight person (BMI < 19)
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Hypotension (< 90/55 mmHG)
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Hypoproteinemia
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Evidence of toxic megacolon
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History of hypersensitivity to heparin
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Heparin-induced thrombocytopenia
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History of cerebrovascular incident
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Known clinically significant bleeding disorder
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Colectomy planned within 6 months
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Concomitant anticoagulant therapy
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History of hypercoagulable disorders
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Severe anaemia or Leukopenia
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Patients with active viral hepatitis and/or human immunodeficiency virus (HIV) infections
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A positive urine pregnancy test at the screening visit
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Patients that are nursing Local intestinal treatments with suppositories, enemas, creams, ointments or foams during the last 2 weeks
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Current daily smoking habits
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Patients unwilling to meet the requirements of the clinical investigational plan
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Other medical or social reasons for exclusion at the discretion of the investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ersta Sjukhus, Medicinkliniken | Stockholm | Sweden | 116 91 |
Sponsors and Collaborators
- TLA, Targeted Immunotherapies AB
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TLA002