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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis Chronic Moderate
• Intervention / Treatment: Biological: Trichuris suis ova; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent
2. Between 18 and 75 years of age
3. Established diagnosis of UC confirmed by endoscopic (sigmoidoscopy) and histological criteria, at least 3 months prior to inclusion
4. 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
5. Mayo-score between 6 and 10 and including 6 and 10 corresponding to moderately active disease
6. Calprotectin ≥ 250 µg/g and an endoscopic Mayo score ≥ 2
7. Negative pregnancy test in females of childbearing potential and the use of an acceptable effective method of contraception
8. 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
9. Tapered down from last oral steroid ≥ 4 weeks ago

Exclusion Criteria:

1. Disease extension corresponding only to E1 (proctitis), i.e. less than 15 cm from the anal verge
2. Bowel surgery, except appendectomy and removal of polyps
3. Septic complications
4. Evidence of infectious diarrhea (i.e. pathogenic bacteria or Clostridium difficile toxin in stool)
5. Abscess, perforation, active fistula or perianal lesions
6. Abnormal hepatic function (ALAT or ALP > 2.5 x ULN at screening), liver cirrhosis, or portal hypertension
7. Abnormal renal function (Creatinine > ULN) at screening
8. 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
9. Any condition associated with significant immunosuppression
10. 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
11. 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)).
12. Treatment with systemic glucocorticosteroid within the last 4 weeks or treatment with topical steroid within the last 2 weeks prior to baseline
13. 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
14. Immunization with live vaccines within 12 weeks prior to baseline or during the trial
15. 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.
16. Well-founded doubt about the patient's cooperation, (e.g., addiction to alcohol or drugs).
17. Existing or intended pregnancy or breast-feeding
18. Participation in another clinical trial within the last 60 days, simultaneous participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ParaTech A/S
• Investigators: Principal Investigator: Andreas M Petersen, MD, Ph.D, Hvidovre University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2018
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Microbiome; Trichuris suis ova; Ulcerative Colitis; IBD; Probiotic; Trichuris suis; Inflammatory bowel diseases; Anti inflammatory; Hygiene Hypothesis; Helminths; MAYO
• 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: PROCTO; 2017-004772-65 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No