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Crohn's Disease RelapsePhase 2AZITRATIMNCT05599347

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

A Phase 2 study testing Azithromycin Pill in people with Crohn's Disease Relapse and Biological Substance; Adverse Effect, run by Rambam Health Care Campus at 9 sites in Israel.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azithromycin Pill
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
180 participants
Where
9 sitesIsrael
Study dates
24 Apr 2023to 10 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Diagnosis of CD with an onset of symptoms for a minimum of 3 months prior to Screening as determined by the investigator based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings.
  • Prior decision of starting infliximab or adalimumab therapy (including biosimilar drugs).
  • Thiopurine and corticosteroid co-therapy will be permitted.
  • Patients who cannot provide informed consent and do not have a legal guardian
Show all 21Show fewer
  • 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
  • Patients who are on chronic therapy which cannot be withheld in one of these medications: colchicine, phenytoin, and digoxin

Who cannot join

None listed.

Trial locations and contacts

9 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Haggai Bar-Yosef, MD contact

050-2064878

h_bar-yoseph@rmc.gov.il

Anastasia Weis, MD contact

A_WEIS@rambam.health.gov.il

9 sites in 1 country

Israel9 sites, 9 recruiting

  • Soroka University Medical Center

    Beersheba

    Doron Schwartz, MD

    Recruiting

  • Rambam Health Care Campus

    Haifa, Haifa District

    Haggai Bar-Yoseph, MD

    Recruiting

  • Bnei Zion

    Haifa

    Tova Rainis, MD

    Recruiting

  • Carmel Medical Center

    Haifa

    Ori Segol, MD

    Recruiting

  • Wolfson Medical Center

    Holon

    Eran Israeli, MD

    Recruiting

  • Hadassah Medical Center

    Jerusalem

    Lior Katz, MD

    Recruiting

  • Shaare Zedek

    Jerusalem

    Ariella Shitrit, MD

    Recruiting

  • Zvulun

    Kiryat Bialik

    Reut Lutski, MD

    Recruiting

  • Rabin Medical Center

    Petah Tikva

    Iris Dotan

    Recruiting

Other trials in Israel

About this study

Official title: Pre-treatment With Azithromycin to Reduce Immunogenicity to Anti-Tumor Necrosis Factor-α Agents in Patients With Crohn's Disease

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

Read the detailed description

Anti-TNF agents are considered the mainstay of therapy for patients with inflammatory bowel diseases (IBD). Still, its efficacy is hampered by the development of anti-drug antibodies (ADA), which lead to non-responsiveness to this medication. A combination with immunosuppressive agents is currently utilized to reduce ADA development but is accompanied by an increased risk of side effects (i.e. malignancy and infections). The investigators have recently found an epidemiologic link between prior antibiotic use and the development of ADA, and shown an antibiotic-specific effect on ADA development in a mouse model. Macrolide antibiotics were specifically associated with ADA prevention and led to increased durability of the treatment. Since the microbiome has been associated with the response to anti-TNF therapy, the investigators hypothesize that microbial manipulation with azithromycin prior to the initiation of anti-TNF therapy will lower ADA development. the investigators propose a randomized controlled study to test our hypothesis and compare it to matched historical cohorts with available clinical and serological data. The primary outcome will be ADA development at 1 year of therapy.

Being tested
Azithromycin Pill, Placebo
Keywords
Crohn's disease, infliximab, adalimumab, azithromycin, immunogenicity
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Azithromycin PillDrug

    Tablet - 500 mg azithromycin (as dihydrate)

  • PlaceboOther

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

Study groups in NCT05599347
Study groupRoleWhat they receive
AzithromycinExperimental5-day consecutive treatment with oral azithromycin 500 mg once daily
Receives: Drug: Azithromycin Pill
ControlPlacebo comparator5-day consecutive oral placebo once daily
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Anti-drug antibody development

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

    Measured: 1 year after the initiation of therapy

Secondary outcomes (12)

  1. Sustained corticosteroid-free clinical remission

    Crohn's Disease Activity Index (CDAI) ≤150 without systemic corticosteroid therapy

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

  2. Clinical response

    A reduction in CDAI of at least 100 points from baseline.

    Measured: 1 year after the initiation of therapy

  3. Sustained corticosteroid-free biochemical remission

    C-reactive protein (CRP) ≤1.5 upper limit of normal, or fecal calprotectin ≤ 250 mg/kg

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

  4. Treatment durability

    Persistent administration of infliximab or adalimumab for 1 year. A 16-week or more interval between infliximab injections, or an 8-week or more interval between adalimumab injections will be considered as treatment cessation. Change in anti-TNF regimen at 26 and 52 weeks defined as increased dosing or decreased dosing interval

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

  5. Anti-TNF drug levels

    Levels at various timepoints

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

  6. Early anti-drug antibody development

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

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

  7. PRO-2 remission at Week 52

    • Patient reported outcome (PRO-2) remission at Week 52 (defined as an abdominal pain [AP] mean daily score at or below 1 [AP≤1] AND a stool frequency [SF] mean daily score at or below 3 [SF≤3], and no worsening of AP or SF from baseline).

    Measured: 1 year after the initiation of therapy

  8. Sustained corticosteroid-free PRO-2 clinical remission

    The rate of sustained corticosteroid-free PRO-2 clinical remission at both 14 and 52 weeks, defined as AP≤1 and SF≤3. The rate of clinical response at 14 weeks, defined as a reduction in CDAI of at least 100 points from baseline

    Measured: At both 14 and a 1 year after the initiation of therapy

  9. Addition of immunomodulator treatment

    The rate of addition of immunomodulator treatment defined as at least one dose of thiopurines or methotrexate

    Measured: At any time during the study

  10. Immunomodulator treatment termination

    The rate of immunomodulator treatment termination. Termination will be defined in patient treated with azathioprine or 6MP at randomization, as being stopped after at least 14 weeks and not restarting by 52 weeks

    Measured: At 14 weeks and not restarting by 1 year after the initiation of therapy

  11. Endoscopic improvement

    Endoscopic improvement defined as a reduction of ≥50% decrement from baseline in SES-CD score

    Measured: At 26 weeks

  12. Endoscopic remission

    Endoscopic remission defined as SES-CD ≤4

    Measured: At 26 and 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2022
  2. Study start24 Apr 2023
  3. Primary completion10 Sep 2026 (estimated)
  4. Study completion10 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
All consenting adults that fulfil the inclusion criteria will be randomized in a 1:1 ratio and allocated to the azithromycin or placebo arms
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
180 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05599347
Sponsor's protocol ID
0432-22-RMB
Acronym
AZITRATIM
Status last verified
Jul 2026
First submitted
14 Sep 2022
Last updated
29 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 34344783

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azithromycin Pill in people with Crohn's Disease Relapse and Biological Substance; Adverse Effect, run by Rambam Health Care Campus at 9 sites in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Haggai Bar-Yosef, MD (050-2064878, h_bar-yoseph@rmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Anti-drug antibody development (time frame: 1 year after the initiation of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05599347, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.

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