Pre-treatment With Azithromycin to Reduce Immunogenicity to to Anti-TNF Agents in Patients With Crohn's Disease

NCT05599347 | Recruiting Phase 2 DMC

• 1 other identifier: 0432-22-RMB
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 9

Brief Summary

This is a randomized placebo-controlled trial in Crohn's disease patients before initiation of anti-tumor necrosis factor-α (anti-TNF) therapy that aims to test the effect of a pre-treatment short course of azithromycin therapy on immunogenicity

Conditions

Crohn's Disease Relapse; Biological Substance; Adverse Effect

Keywords

Crohn's disease; infliximab; adalimumab; azithromycin; immunogenicity

Outcome Measures

Primary Outcomes (1)

• Anti-drug antibody development

  Percent of patients developing anti-drug antibodies defined as measurable antibodies using an anti-lambda ELISA assay

  1 year after the initiation of therapy

Secondary Outcomes (12)

• Sustained corticosteroid-free clinical remission

  At both 3 months and a 1 year after the initiation of therapy

• Clinical response

  1 year after the initiation of therapy

• Sustained corticosteroid-free biochemical remission

  at both 6 months and a 1 year after the initiation of therapy

• Treatment durability

  at both 6 months and a 1 year after the initiation of therapy

• Anti-TNF drug levels

  At 6 weeks, 26 weeks and a 1 year after the initiation of therapy

Study Arms (2)

Azithromycin

EXPERIMENTAL

5-day consecutive treatment with oral azithromycin 500 mg once daily

Drug: Azithromycin Pill

Control

PLACEBO COMPARATOR

5-day consecutive oral placebo once daily

Other: Placebo

Interventions

Azithromycin Pill DRUG

Tablet - 500 mg azithromycin (as dihydrate)

Azithromycin

Placebo OTHER

Placebo tablet identical in shape and appearance to the azithromycin tablet used in the treatment arm

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent prior to any study procedures and willing and able to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study period.
• Aged 18 to 80 years of age, inclusive, at the time of signing the informed consent.
• Prior decision of starting infliximab or adalimumab therapy (including biosimilar drugs).
• Thiopurine and corticosteroid co-therapy will be permitted.

You may not qualify if:

• Patients who cannot provide informed consent and do not have a legal guardian
• Patients with perianal involvement who are expected to require antibiotic therapy for their disease
• Patients on chronic antibiotic therapy due to any cause
• Patients with ongoing fluid collection/abscess either internal or perianal
• Known history of allergy to the study intervention formulation or any of its excipients or components of the delivery device
• Prolonged QTc interval or conditions leading to additional risk for QT prolongation
• Chronic kidney disease stage 5 (GFR \< 10)
• Crohn's Disease complication requiring surgical treatment
• Planned/ongoing methotrexate co-therapy
• Fecal microbiota transplantation within 8 weeks prior to randomization
• Participant has any disorder that, in the opinion of the investigator, may compromise the ability to participate in the study
• Pregnancy
• Patients who received azithromycin therapy in the previous year (we will not exclude prior use of other antibiotic therapy)
• Patients who received any antibiotic treatment within 4 weeks prior to randomization
• Re-induction of the same anti-TNF medication

Sponsors & Collaborators

• Rambam Health Care Campus: lead

Study Sites (9)

Soroka University Medical Center

Beersheba, Israel

RECRUITING

Bnei Zion

Haifa, Israel

RECRUITING

Carmel Medical Center

Haifa, Israel

RECRUITING

Rambam Health Care Campus

Haifa, Israel

RECRUITING

Wolfson Medical Center

Holon, Israel

RECRUITING

Hadassah Medical Center

Jerusalem, Israel

RECRUITING

Shaare Zedek

Jerusalem, Israel

RECRUITING

Zvulun

Kiryat Bialik, Israel

RECRUITING

Rabin Medical Center

Petah Tikva, Israel

RECRUITING

Related Publications (1)

• Gorelik Y, Freilich S, Gerassy-Vainberg S, Pressman S, Friss C, Blatt A, Focht G, Weisband YL, Greenfeld S, Kariv R, Lederman N, Dotan I, Geva-Zatorsky N, Shen-Orr SS, Kashi Y, Chowers Y; IIRN. Antibiotic use differentially affects the risk of anti-drug antibody formation during anti-TNFalpha therapy in inflammatory bowel disease patients: a report from the epi-IIRN. Gut. 2022 Feb;71(2):287-295. doi: 10.1136/gutjnl-2021-325185. Epub 2021 Aug 3.

  PMID: 34344783 RESULT

MeSH Terms

Conditions

Crohn Disease

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Central Study Contacts

Haggai Bar-Yosef, MD

CONTACT

050-2064878; h_bar-yoseph@rmc.gov.il

Anastasia Weis, MD

CONTACT

A_WEIS@rambam.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind masking
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: All consenting adults that fulfil the inclusion criteria will be randomized in a 1:1 ratio and allocated to the azithromycin or placebo arms

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: October 31, 2022
• Study Start: April 24, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-04

Locations

IL (9)