Efficacy of optimized thiopurine therapy in ulcerative colitis.

• Register: EUCTR
• Last refreshed on: 31 October 2016
• Main ID: EUCTR2015-005260-41-NL
• Date of registration: 15/02/2016
• Prospective Registration: Yes
• Primary sponsor: Academic Medical Centre
• Public title: Efficacy of optimized thiopurine therapy in ulcerative colitis.
• Scientific title: Efficacy of optimized thiopurine therapy in ulcerative colitis. - OPTIC
• Date of first enrolment: 13/10/2016
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005260-41
• 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): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Mark Löwenberg
• Affiliation: Academic Medical Centre

• Name: Mark Löwenberg
• Affiliation: Academic Medical Centre

Key inclusion & exclusion criteria

Inclusion criteria:
1. Confirmed diagnosis of UC by endoscopy and histopathology
2. Patients between 18 and 80 years of age
3. Active disease, despite oral treatment with at least 2g/day 5-ASA
4. Treatment with oral corticosteroids is required
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 26

Exclusion criteria:
1. Prior treatment with thiopurines
2. Prior treatment with biologics (e.g. anti-TNF agents and vedolizumab)
3. Current pregnancy (a pregnancy test will be performed if necessary according to the treating physician.)
4. Chronic Obstructive Pulmonary Disease (COPD)
5. Acute coronary heart disease
6. (Bacterial) gastroenteritis has to be treated first
7. Coagulation disorders
8. Active malignancy
9. History of colonic dysplasia/cancer
10. Extensive colonic resection, i.e. subtotal colectomy with less than 15 cm colon in situ
11. Concomitant therapy with drugs interfering with MP metabolism, like allopurinol, ribavirin or anti-epileptics.
12. Known systemic fungal infections or parasitic infections have to be treated first
13. Known duodenal or ventricular ulcus
14. Substance abuse, such as alcohol (at least 80 gram/day – one standard glass contains 10 gram of alcohol), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded
15. Positive tuberculosis screen (when a screening is performed at the discretion of the treating physician)
16. Active hepatitis B virus or hepatitis C virus infection defined as a positive anti-HCV, HBsAg and/or anti-HBcore screening.
17. Leucopenia (Neutrophil count below 1,8x10^9/L)
18. Thrombopenia (Platelets below 90x10^9/L)
19. Elevated liver enzymes (over 2x ULN)
20. Abnormal renal function (eGFR below 30 mL/min)
21. Other conditions which in the opinion of the investigator may interfere with the subject’s ability to comply with the study procedure


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: 19.0 Level: SOC Classification code 10017947 Term: Gastrointestinal disorders System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Trade Name: Mercaptopurine (Puri-Nethol)
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The main endpoint of this study is clinical and endoscopic remission, which we defined as a SCCAI-score of maximum 4, a UCEIS-score of maximum 3 and a total Mayo-score of maximum 2, with no individual subscore above 1.

Secondary Objective: Secondary objectives are to conduct a cost-utility and budget impact analysis of optimized thiopurine therapy and to identify biomarkers as potential predictors of thiopurine response in mucosal biopsies, feces and blood.

Main Objective: The primary objective of the proposed this study is to evaluate the efficacy of optimized thiopurine therapy. Therapeutic drug monitoring (TDM) will be applied in order to optimize treatment outcomes and objective endoscopic endpoints will be used. Optimized use of thiopurines may lead to prolonged and better disease outcome and avoidance of costly biological therapy or surgery.

Timepoint(s) of evaluation of this end point: One year after start of the treatment (week 52)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Different time-points during one year of treatment.

Secondary end point(s): - Occurrence of (serious) adverse events ((S)AE)
- Leukocyte counts
- Liver function tests
- Occurrence of subjective thiopurine intolerance
- 6-TGN levels
- 6-MMP levels
- Occurrence of treatment failure
- Occurrence of flares and upscaling treatment / escape medication
- Treatment costs
- Quality of life
- Biomarkers, cell types and microbiome in colon biopsies
- Fecal Volatile Organic Compounds (VOC's)
- Fecal microbiome sequencing
- RAC genotypes in blood samples

Secondary ID(s)

NCT02910245

SA652012

Source(s) of Monetary Support

ZonMw