Personalized AZithromycin/metronidAZole, in Combination With Standard Induction Therapy, to Achieve a Fecal Microbiome Community Structure and Metagenome Changes Associated With Sustained Remission in Pediatric Crohn's Disease (CD): a Pilot Study

19-3100

This is a multi-center, randomized, controlled open-label add-on design trial pilot study to evaluate the efficacy of personalized adjunctive antibiotic (azithromycin + metronidazole) therapy in pediatric subjects with mild to moderate Crohn's disease (CD) who have a microbiome profile associated with increased risk of early relapse. This an add-on design trial for subjects already receiving standard of care therapy to induce remission; there will be no placebos.

2021-08-13

2023-12-01

2023-12-01

Recruiting

Early phase I

20

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. Fecal calprotectin level \>=250 µg/g within 30 days prior to week 0 visit based on local measurement, if available, or to be arranged with lead site if an endoscopy is not performed within 30 days prior to week 0 visit. Exclusion Criteria: 1. Current or previous use of biologic therapy; 2. Presence of stricturing, penetrating (intestinal or perianal) and/or fistulizing CD; 3. Pregnancy or lactation; 4. Have undergone intestinal resection; 5. Positive Clostridium Difficile toxin; 6. Treatment with another investigational drug or other intervention within 30 days before week 0; 7. Risk factors for arrhythmia including history of prolonged corrected QT interval (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 intravenous anti-infective within 35 days prior to week 0 visit or 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 methotrexate (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: * aspartate transaminase (AST), alanine transaminase (ALT) \> 2 X upper limit of the reference range, * White blood cell (WBC) count \< 3.0 X 109/L, * Total bilirubin \>= 20 micromol/liter (1.17 mg/dL); except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome, * Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula of \< 30 mL/min/1.73 m², * Hemoglobin \< 80 gram/liter, * Platelets \< 100,000/µL.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2023-10-04