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

NCT04186247 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-3100585718
• Study Type: interventional
• Target: 13
• Locations: 4 countries
• Sites: 5

Brief 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.

Conditions

Crohn Disease; Pediatric Crohns Disease

Keywords

Microbiome

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Sustained Remission

  Participants stratified based on carriage of an at-risk microbiome without need for re-induction for clinical flare (new course of nutritional therapy, need to restart steroids), steroid dependence, biologic (e.g. anti-TNF) use, and/or intestinal surgery.

  Week 52

• Feasibility of Multinational Microbiome-randomized Trial

  The number of participants with microbiome data available at Week 4/5.

  Week 4/5

Secondary Outcomes (4)

• Number of Participants With Normal Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52

  Week 52

• Number of Participants With Normal Fecal Calprotectin Levels in Stool at Week 52

  Week 52

• Number of Participants With Normal C-Reactive Protein (CRP) Levels in Blood at Week 52

  Week 52

• IMPACT-III Score at Week 52

  Week 52

Study Arms (2)

Standard of Care

OTHER

SOC induction (nutritional therapy) for up to 12 weeks, as assigned by the treating gastroenterologist prior to study entry.

Other: Standard of Care

Standard of Care + Antibiotics

EXPERIMENTAL

SOC induction (nutritional therapy) for up to 12 weeks, as assigned by the treating gastroenterologist prior to study entry. Azithromycin (weeks 4-12) Metronidazole (weeks 4-12)

Drug: Azithromycin; Drug: Metronidazole; Other: Standard of Care

Interventions

Azithromycin DRUG

Weeks 4-12: 7.5 mg/kg azithromycin once daily (500 mg/day maximum) for five consecutive days/ week for 4 weeks, and 3 times a week for the following 4 weeks

Also known as: Zithromax, Zmax

Standard of Care + Antibiotics

Metronidazole DRUG

Weeks 4-12: 20 mg/kg/day of metronidazole (10 mg/kg twice daily to a maximum of 1000 mg/day) for 8 weeks

Also known as: Flagyl

Standard of Care + Antibiotics

Standard of Care OTHER

SOC induction therapy is nutritional therapy (Crohn's disease exclusion diet + partial enteral nutrition) for up to 12 weeks. Induction therapy is as assigned by the treating gastroenterologist prior to study entry.

Standard of Care; Standard of Care + Antibiotics

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Provision of signed and dated informed consent form (and assent form, as applicable);
• Stated willingness to comply with all study procedures and availability for the duration of the study;
• Male or female, aged 3 to 17 years;
• Diagnosed with CD according to standard clinical and histological criteria, within 36 months of week 0;
• Exhibiting mild to moderate symptoms of active disease, as determined by a Pediatric Crohn's Disease Activity Index (PCDAI) score \>10 (or \> 7.5 excluding the height item) and ≤37.5;
• 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.

You may not qualify if:

• Current or previous use of biologic therapy;
• Presence of stricturing, penetrating (intestinal or perianal) and/or fistulizing CD;
• Pregnancy or lactation;
• Have undergone intestinal resection;
• Positive Clostridium Difficile toxin;
• Treatment with another investigational drug or other intervention within 30 days before week 0;
• 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;
• History of cockayne syndrome;
• Prior diagnosis of any hematologic condition/blood dyscrasia which may result in leukopenia (even if leukocyte count is normal at screening);
• Known allergy or intolerance to azithromycin or metronidazole;
• 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;
• 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;
• Subject who received fecal microbial transplantation within 35 days prior to week 0 visit;
• 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,

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Crohn's and Colitis Foundation: collaborator
• University of Amsterdam: collaborator
• OM Pharma SA: collaborator

Study Sites (5)

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

IWK Health Centre

Halifax, Canada

Location

Wolfson Medical Centre

Tel Aviv, Israel

Location

Amsterdam UMC

Amsterdam, Netherlands

Location

Related Publications (1)

• Verburgt CM, Dunn KA, Otley A, Heyman MB, Verstraete S, Sunseri W, Sylvester F, de Meij T, Comeau A, Langille M, de Jonge WJ, Benninga MA, Van Limbergen JE. Personalised azithromycin+metronidazole (PAZAZ), in combination with standard induction therapy, to achieve a faecal microbiome community structure and metagenome changes associated with sustained remission in paediatric Crohn's disease (CD): protocol of a pilot study. BMJ Open. 2023 Feb 1;13(2):e064944. doi: 10.1136/bmjopen-2022-064944.

  PMID: 36725090 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Azithromycin; Metronidazole; Standard of Care

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Johan Van Limbergen, MD, PhD
• Organization: Amsterdam University Medical Center

j.e.vanlimbergen@amsterdamumc.nl

+31-20 566 9111

Study Officials

• Johan E Van Limbergen, MD, PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

• Arie Levine, MD

  Edith Wolfson Medical Centre, Tel Aviv

  STUDY CHAIR

• Francisco Sylvester, MD

  University North Carolina

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 4, 2019
• Study Start: August 13, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: June 29, 2025
• Results First Posted: June 29, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning 9 to 36 months following publication
• Access Criteria: IRB, IEC, or REB approval, as applicable, and an executed data use/sharing agreement with University of North Carolina.

Locations

NL (1); IL (1); CA (1); US (2)