Probiotic Treatment of Ulcerative Colitis With Trichuris Suis Ova (TSO)

Study Overview
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Brief Summary
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The PROCTO trial is a double-blind randomized, placebo-controlled, 24-week, comparative, exploratory phase II proof of concept trial. The trial will be conducted with 2 treatment groups as a parallel group comparison and will serve to compare a 7500 TSO regimen vs. placebo for achieving clinically meaningful responses in Ulcerative Colitis.

Official Title
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Probiotic Treatment of Ulcerative Colitis With Trichuris Suis Ova (TSO)

Conditions
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Ulcerative Colitis Chronic Moderate

Intervention / Treatment
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* Biological: Trichuris suis ova
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Between 18 and 75 years of age Established diagnosis of UC confirmed by endoscopic (sigmoidoscopy) and histological criteria, at least 3 months prior to inclusion Disease extension corresponding to E2 (left side colitis) or E3 (extensive colitis) according to the Montreal Classification, i.e. at least 15 cm from anal verge, confirmed by an index sigmoidoscopy Mayo-score between 6 and 10 and including 6 and 10 corresponding to moderately active disease Calprotectin ≥ 250 µg/g and an endoscopic Mayo score ≥ 2 Negative pregnancy test in females of childbearing potential and the use of an acceptable effective method of contraception No treatment or if treated with 5-Aminosalicyl acid (5-ASA): 5-ASA ≥ 8 weeks with a stable dose for at least 4 weeks both oral and rectal use Tapered down from last oral steroid ≥ 4 weeks ago Exclusion Criteria: Disease extension corresponding only to E1 (proctitis), i.e. less than 15 cm from the anal verge Bowel surgery, except appendectomy and removal of polyps Septic complications Evidence of infectious diarrhea (i.e. pathogenic bacteria or Clostridium difficile toxin in stool) Abscess, perforation, active fistula or perianal lesions Abnormal hepatic function (ALAT or ALP > 2.5 x ULN at screening), liver cirrhosis, or portal hypertension Abnormal renal function (Creatinine > ULN) at screening Any severe concomitant cardiovascular, renal, endocrine, or psychiatric disorder, which in the opinion of the investigator might have an influence on the patient's compliance or the interpretation of the results Any condition associated with significant immunosuppression Treatment with immunosuppressants or anti-cancer drugs, e.g., anti-TNF-α agents, anti-integrin agents, azathioprine or 6-MP, 6-thioguanine, methotrexate, tacrolimus, cyclophosphamide, or cyclosporine within the last 3 months prior to baseline Treatment with systemic broad-spectrum antibiotics (e.g. metronidazole or ciprofloxacin), anti-parasitic medications, or probiotic (e.g. fecal transplantation) medication within the last 4 weeks prior to baseline, except for probiotic lactobacillus or bifidobacteria within 2 week prior to baseline (and minimum 1 week before screening visit (sampling and biopsies)). Treatment with systemic glucocorticosteroid within the last 4 weeks or treatment with topical steroid within the last 2 weeks prior to baseline Application of systemic non-steroidal anti-inflammatory drugs (NSAIDs) within 2 weeks before baseline visit for more than 3 consecutive days, except acetylsalicylic acid ≤ 350 mg/d which is allowed Immunization with live vaccines within 12 weeks prior to baseline or during the trial Travelling to rural districts in countries outside of Europe, USA, Australia or Canada within the last 12 weeks prior to baseline or during trial participation. If patients travel outside of Europe, USA, Australia or Canada they must be tested negative in the standard stool tests (parasites, bacteria and virus) when they return, as at the screening visit. Well-founded doubt about the patient's cooperation, (e.g., addiction to alcohol or drugs). Existing or intended pregnancy or breast-feeding Participation in another clinical trial within the last 60 days, simultaneous participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Double-blind randomised, placebo-controlled, 24 weeks, comparative, exploratory phase II proof of concept trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Trichuris suis ova (TSO)<br>7500 TSO suspension, orally every second week for 24 weeks. | Biological: Trichuris suis ova<br>* Eggs from the pig whipworm<br>* Other names: TSO;|
| Placebo Comparator: Placebo<br>Solution without TSO orally every second week for 24 weeks | Biological: Placebo<br>* Solution without TSO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission (Full Mayo) | To achieve clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (ITT, PP). The full Mayo score (range 0-12) is the sum of 4 clinical scores (stool frequency, rectal bleeding, mucosal appearance at endoscopy, physician rating of disease activity) each scored with a value 0 (normal), 1, 2, or 3 (worst). | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response (Full Mayo) | To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (ITT, PP, complete steroid-free) | 24 weeks | 
| Steroid free remission (Full Mayo) | To achieve complete steroid free clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (complete steroid-free) | 24 weeks | 
| Endoscopic remission | To achieve endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (long-term efficacy) (ITT, PP, complete steroid-free) | 24 weeks | 
| Symptomatic remission | To achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks (short-term efficacy) and at 24 weeks (long-term efficacy) (ITT, PP, complete steroid-free) | 12 and 24 weeks | 
| Time to remission | To reduce time to achieve remission defined as time to achieve a pMayo score ≤ 1 and time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (ITT, PP, complete steroid-free) | 0-24 weeks | 
| Time to response | To reduce time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (ITT, PP, complete steroid-free) | 0-24 weeks | 
| Disease severity | To decrease disease severity assessed by pMayo scores at 12 to 24 weeks | 12-24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Trichuris suis, Trichuris suis ova, Probiotic, IBD, Inflammatory bowel diseases, Anti inflammatory, Hygiene Hypothesis, Helminths, Microbiome, MAYO