Crohn's Disease
Conditions
Interventions
Trade Name: Azithromycin
Product Name: Azithromycin
Pharmaceutical Form: Tablet
INN or Proposed INN: Azithromycin
Other descriptive name: AZITHROMYCIN
Trade Name: Metronidazole
Product Name: Metronid
Sponsors
Amsterdam UMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated informed consent form (and assent form, as applicable) 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, aged 3 to 17 years 4. Diagnosed with CD according to standard clinical and histological criteria, within 36 months of week 0 5. Exhibiting mild to moderate symptoms of active disease, as determined by a PCDAI score >10 (or >7.5 excluding the height item) and =37.5 6. Evidence of active inflammation based on either: fecal calprotectin level >=250 microgram/g (local laboratory or pre-arranged sponsor testing) within 30 days prior to week 0 visit; or according to accepted endoscopic and histologic evidence obtained during an endoscopy procedure completed within 30 days prior to Week 0 Visit. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1.Current or previous use of anti-TNF or other biologic therapy 2.Presence of stricturing, penetrating (intestinal or perianal) and/or fistulizing CD. 3.Pregnancy or lactation 4.Have undergone intestinal resection 5.Laboratory diagnosis of Clostridium Difficile Infection (CDI), if performed for clinical indication 6.Treatment with another investigational drug or other intervention within 30 days before week 0 7.Risk factors for arrhythmia including history of prolonged QTc, hypokalemia or hypomagnesemia, resting bradycardia, or concurrent treatment with other drugs with potential for QT prolongation. 8.History of Cockayne syndrome 9.Prior diagnosis of any hematologic condition/blood dyscrasia which may result in leukopenia (even if leukocyte count is normal at screening) 10.Known allergy or intolerance to azithromycin or metronidazole 11.Subjects who received IV anti-infective within 35 days prior to week 0 visit or oral anti-infectives within 14 days prior to the week 0 visit. 12.Subject on oral aminosalicylates who has not been on stable doses for greater than, or discontinued within, at least 14 days prior to week 0. 13.Subject on cyclosporine, tacrolimus or mycophenolate mofetil. Stable doses (no change within 14 days prior to week 0) of Azathioprine, 6-mercaptopurine or MTX are not a reason for exclusion. 14.Subject who received fecal microbial transplantation within 35 days prior to week 0 visit. 15.Screening laboratory and other analyses show any of the following abnormal results: o AST, ALT > 2 X upper limit of the reference range (as determined locally at each site) o Urea, Creatinine > 1.5X upper limit of the reference range (as determined locally at each site) o White blood cell (WBC) count = 20 micromol/liter (1.17mg/dl); except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome o Hemoglobin < 80 gram/liter o Platelets < 100,000/µL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the potential efficacy of personalized adjunctive antibiotic therapy in maintaining clinical remission in pediatric subjects undergoing SOC induction therapy for mild to moderate Crohn’s disease who have a relapse-associated microbiome profile ;Secondary Objective: The secondary objectives are to evaluate the potential efficacy of personalized adjunctive antibiotic therapy in improving PRO, components of established disease activity measures in remission, as well as ‘biochemical’ remission in pediatric subjects undergoing SOC induction therapy for mild to moderate Crohn’s disease who have a relapse-associated microbiome profile. The exploratory objective is to investigate relationship between changes in subject microbiome composition and changes in disease activity over time.;Primary end point(s): Primary Outcome variable: Sustained remission defined as no need of re-induction for clinical flare (new course of nutritional therapy, need to start steroids), steroid dependence, biologic (anti-TNF) use, and/or intestinal surgery by 12 months.;Timepoint(s) of evaluation of this end point: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Outcome variables: Longitudinal (clustered and with respect to baseline) changes in disease activity indices (PCDAI: 0-100) components and inflammatory markers in stool and blood at each study visit up to 12 months. Longitudinal (clustered and with respect to baseline) changes in patient-reported outcomes (PRO) by 12 months. Exploratory Outcome variable: Longitudinal (clustered and with respect to baseline) changes in fecal microbiome taxonomic composition or in total gene (metagenome) content. The changes will be analyzed for association with changes in disease activity (e.g. relapse or sustained remission) over time up to 12 months.;Timepoint(s) of evaluation of this end point: 52 weeks | — |
Countries
Canada, Israel, Netherlands, United States
Contacts
Public ContactCharlotte Verburgt
Amsterdam UMC
Outcome results
None listed