Personalized AZithromycin/metronidAZole Therapy in Pediatric Crohn's Disease (CD)

• Status: Not yet recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Crohn's and Colitis Foundation; University of Amsterdam
• Treatments: Azithromycin; Metronidazole

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. 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.