Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova (TSO)

• Register: EUCTR
• Last refreshed on: 14 March 2022
• Main ID: EUCTR2017-004772-65-DK
• Date of registration: 04/12/2017
• Prospective Registration: Yes
• Primary sponsor: ParaTech A/S
• Public title: Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova (TSO)
• Scientific title: Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova (TSO) - PROCTO
• Date of first enrolment: 05/02/2018
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004772-65
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Denmark

Contacts

• Name: CEO, Professor, PhD
• Affiliation: ParaTech A/S

• Name: CEO, Professor, PhD
• Affiliation: ParaTech A/S

Key inclusion & exclusion criteria

Inclusion criteria:
Patients who meet all of the following criteria can be enrolled into the trial:
1. Signed informed consent
2. Between 18 and 75 years of age
3. Established diagnosis of UC confirmed by endoscopic (sigmoidoscopy) and histological criteria, within 3 months prior to screening
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 birth control
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Patients who meet one of the following criteria, are not allowed to be enrolled into the trial:
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 (e.g. 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-a 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. facal transplantation) medication within the last 4 weeks prior to baseline, except for probiotic lactobacillus or bifidobacteria within 2 weeks 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 (the Corona vaccines are not per se live vaccine)
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Code: TSO
Pharmaceutical Form: Suspension for oral suspension
INN or Proposed INN: TSO
Other descriptive name: SUSPENSION CONTAINING 7500 EMBRYONATED VIABLE TRICHURIS SUIS OVA/15ML
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: range
Concentration number: 450-550
Pharmaceutical form of the placebo: Suspension for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Full Mayo: Measurements at week -2 to -1 at the screenings visit and at 24 week as sigmoidoscopy will be performed to be able to calculate full Mayo score

Secondary Objective: The patients should achieve a clinically meaningful response defined as reduction in full Mayo disease score, complete steroid free clinical remission, endoscopic remission, symptomatic remission, time to achieve disease remission (as defined by pMayo score), time to achieve disease response (as defined by pMayo score) and decrease in disease severity over time assessed by pMayo scores (secondary endpoints). Further, the PROCTO trial aims to evaluate steroid use, patient withdrawals due to worsening of disease, mucosal healing, and a reduction in the inflammatory biomarker calprotectin and to explore 1) a local and systemic immune therapeutic effect through antibody stimulation and cytokine regulation, and 2) a shift in the gut microbiota profile to down regulate pro-inflammatory bacteria in UC patients and 3) the patient-reported outcome.

Primary end point(s): Primary endpoint
• To achieve clinical remission defined as full Mayo score = 2 at 24 weeks (long-term efficacy) (ITT, PP)

Main Objective: The objectives of the present “PROCTO” trial is to demonstrate that administration of 7500 TSO every second week over 24 weeks will reduce the intestinal inflammation in moderate UC by achieving clinical remission by full Mayo disease score (primary endpoint).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Full Mayo: Measurements at week -2 to -1 at the screenings visit and at 24 week as sigmoidoscopy will be performed to be able to calculate full Mayo score
pMayo: Measurements at week -2 to -1, 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and at the follow visit week 30

Secondary end point(s): Secondary endpoints
• To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (ITT, PP, complete steroid-free)
• To achieve complete steroid free clinical remission defined as full Mayo score = 2 at 24 weeks (long-term efficacy) (complete steroid-free)
• 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)
• 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)
• 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)
• 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)
• To decrease disease severity assessed by pMayo scores at visit 7 to 13.

Secondary ID(s)

PROCTO

Source(s) of Monetary Support

ParaTech A/S

Ethics review

Status: Approved
Approval date: 05/02/2018
Contact: