Crohn DiseasePhase 4NCT04966585
Pilot Study of Posaconazole in Crohn's Disease
A Phase 4 study testing Posaconazole Delayed Release Oral Tablet in people with Crohn Disease and CARD9 S12N Risk Allele, run by Cedars-Sinai Medical Center at 2 sites in United States.
Trial summary
This trial is designed to evaluate the effects of oral antifungal treatment with posaconazole on active Crohn's disease (CD) activity and the burden of Malassezia spp. in CD patients with the caspase recruitment domain family member 9 (CARD9) S12N risk allele. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Crohn Disease, CARD9 S12N Risk Allele
- What is being tested?
- Posaconazole Delayed Release Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Aug 2022to 22 Jan 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female patients aged 18 years and older, inclusive based on the date of the screening visit.
- A diagnosis of CD with minimum disease duration of 6 months with involvement of the ileum and/or colon documented on colonoscopy
- Have an endoscopically-confirmed active Crohn's disease with active disease defined by SES-CD > 6 (>4 if ileal only), AND active symptoms of Crohn's disease (CDAI score >220)
- Homozygous for CARD9 S12N risk allele, without the protective exon 11 polymorphism
- Subjects receiving oral aminosalicylates (at a stable dose for 2 weeks prior to baseline), immunomodulators (at a stable dose for 4 weeks prior to baseline), anti-TNF, anti IL12/23, or anti-integrin therapy (at stable maintenance doses for > 8 weeks) may continue their use during the study.
- Subjects receiving oral corticosteroids may continue their use during the study provided the dose (prednisone up to 20 mg/day, budesonide up to 9 mg/day) has been stable for two weeks prior to screening.
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- Have had age-appropriate and disease-duration-appropriate colon cancer screening1 without unresected dysplasia.
- Women of childbearing age, excluding those with prior bilateral tubal ligation or at least one-year post-menopause, must not be pregnant, lactating, or planning to become pregnant. They must agree to use effective contraception throughout the study period.
- Subjects must be able to provide informed consent and understand, agree with, and be able to adhere to daily diary entries, all scheduled visits, tests, procedures, and protocol in English.
Who cannot join
- Known hypersensitivity or allergy to posaconazole or other azole antifungal agents
- Concomitant medications primarily metabolized by CY3PA4 including: a) Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, primarily metabolized by CY3PA4 (increases risk of rhabdomyolysis), b) Sirolimus, c) Ergot alkaloids, d) vincristine
- Proarrhythmic conditions
- Moderate or severe renal impairment (Cr Clearance <50)
- Current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, infectious colitis, or microscopic colitis.
- Fulminant colitis, toxic megacolon, peritonitis, ileostomy or colostomy.
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- Stool sample positive for pathogens including ova and parasites, Salmonella, Shigella, and C. difficile at screening.
- History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease or any other medical condition that, in the Investigators opinion, would prevent the subject from participation in the study.
- Treatment with antibiotics, antifungal agents, probiotics, or prebiotics within two weeks of screening.
- Alcohol or drug abuse (in the opinion of the Investigator) that would interfere with compliance.
- Any other investigational therapy or treatment within four weeks of screening.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cedars-Sinai Medical Center (CSMC)
Los Angeles, California, 90048
Mayo Clinic
Rochester, Minnesota, 55901
About this study
Official title: A Multicenter Randomized, Double-Blinded, Placebo-Controlled Study of Posaconazole in Genetically-Defined Patients With Active Crohn's Disease
This trial is designed to evaluate the effects of oral antifungal treatment with posaconazole on active Crohn's disease (CD) activity and the burden of Malassezia spp. in CD patients with the caspase recruitment domain family member 9 (CARD9) S12N risk allele. Further, this project will investigate the hypothesis that the microbial changes induced by antifungal treatment are associated with dampened downstream immune responses in those with a genetic predisposition to developing strong immune responses to Malassezia.
- Conditions
- Crohn Disease, CARD9 S12N Risk Allele
- Being tested
- Posaconazole Delayed Release Oral Tablet, Matching Placebo Tablet
- Keywords
- Crohn's, Malassezia, CARD9 S12N, Antifungal
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Posaconazole Delayed Release Oral TabletDrug
Also called Noxafil
Three 100mg delayed-release tablets twice a day on the first day, then three 100mg delayed-release tablets once a day, starting on the second day. Duration of therapy will be 12 weeks.
Matching Placebo TabletDrug
Three matching placebo tablets twice a day on the first day, then three tablets once a day, starting on the second day. Duration of therapy will be 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Posaconazole | Experimental | Subjects administered posaconazole (Noxafil®, Merck) 300mg twice daily for 1 day followed by 300mg daily for 12 weeks Receives: Drug: Posaconazole Delayed Release Oral Tablet |
| Placebo | Placebo comparator | Subjects administered three matching placebo tablets twice daily for 1 day followed by three tablets daily for 12 weeks Receives: Drug: Matching Placebo Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Medically Defined Endoscopic Response
Defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.
Measured: Week 12
Secondary outcomes (3)
Induction of Clinical Remission
Defined as Patient-Reported Outcome (PRO2) abdominal pain score ≤1 AND stool frequency ≤3, and Crohn's Disease Activity Index (CDAI) (<150).
PRO2 is the weighted average of the 2 variables of frequency of liquid or very soft stool and abdominal pain, based on 7-day participant diary data. The PRO2 score has a minimum score of 0 and has no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain.
The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.
Measured: Week 12
Change in Amount of Concomitant Medications
Measured: Week 12
Proportion of Subjects in Endoscopic Remission
Defined as a Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≤3. The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 56, with higher scores indicating more severe disease.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2021
- Study start17 Aug 2022
- Primary completion22 Jan 2025
- Study completion22 Jan 2025
Why it stopped: Recruitment challenges; changes in manufacturing
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomly assigned to receive posaconazole or placebo in 1:1 fashion.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gil Melmed, Cedars-Sinai Medical Center
- Investigators
- Gil Y Melmed, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04966585
- Sponsor's protocol ID
- MOD03104
- Other IDs
- 1R01DK125495-01A1
- Status last verified
- Feb 2026
- First submitted
- 8 Jul 2021
- Last updated
- 24 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized, Double-Blinded, Placebo-Controlled Study of Posaconazole in Genetically-Defined Patients With Active Crohn's Disease
- ClinicalTrials.gov ID
- NCT04966585
- Acronym / sponsor ID
- MOD03104
- Conditions
- Crohn Disease, CARD9 S12N Risk Allele
- Keywords
- Crohn's, Malassezia, CARD9 S12N, Antifungal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment challenges; changes in manufacturing
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 17 Aug 2022 (actual)
- Primary completion
- 22 Jan 2025 (actual)
- Study completion
- 22 Jan 2025 (actual)
- First posted
- 19 Jul 2021 (actual)
- Results
- Posted 24 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is designed to evaluate the effects of oral antifungal treatment with posaconazole on active Crohn's disease (CD) activity and the burden of Malassezia spp. in CD patients with the caspase recruitment domain family member 9 (CARD9) S12N risk allele. Further, this project will investigate the hypothesis that the microbial changes induced by antifungal treatment are associated with dampened downstream immune responses in those with a genetic predisposition to developing strong immune responses to Malassezia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomly assigned to receive posaconazole or placebo in 1:1 fashion.
| Arm | Type | Receives |
|---|---|---|
| Posaconazole | Experimental | Drug: Posaconazole Delayed Release Oral TabletSubjects administered posaconazole (Noxafil®, Merck) 300mg twice daily for 1 day followed by 300mg daily for 12 weeks |
| Placebo | Placebo comparator | Drug: Matching Placebo TabletSubjects administered three matching placebo tablets twice daily for 1 day followed by three tablets daily for 12 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male or female patients aged 18 years and older, inclusive based on the date of the screening visit.
- A diagnosis of CD with minimum disease duration of 6 months with involvement of the ileum and/or colon documented on colonoscopy
- Have an endoscopically-confirmed active Crohn's disease with active disease defined by SES-CD > 6 (>4 if ileal only), AND active symptoms of Crohn's disease (CDAI score >220)
- Homozygous for CARD9 S12N risk allele, without the protective exon 11 polymorphism
- Subjects receiving oral aminosalicylates (at a stable dose for 2 weeks prior to baseline), immunomodulators (at a stable dose for 4 weeks prior to baseline), anti-TNF, anti IL12/23, or anti-integrin therapy (at stable maintenance doses for > 8 weeks) may continue their use during the study.
Key exclusion criteria (11 listed)
- Known hypersensitivity or allergy to posaconazole or other azole antifungal agents
- Concomitant medications primarily metabolized by CY3PA4 including: a) Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, primarily metabolized by CY3PA4 (increases risk of rhabdomyolysis), b) Sirolimus, c) Ergot alkaloids, d) vincristine
- Proarrhythmic conditions
- Moderate or severe renal impairment (Cr Clearance <50)
- Current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, infectious colitis, or microscopic colitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Posaconazole Delayed Release Oral TabletAlso: NoxafilThree 100mg delayed-release tablets twice a day on the first day, then three 100mg delayed-release tablets once a day, starting on the second day. Duration of therapy will be 12 weeks. | Drug | Posaconazole |
| Matching Placebo TabletThree matching placebo tablets twice a day on the first day, then three tablets once a day, starting on the second day. Duration of therapy will be 12 weeks. | Drug | Placebo |
Primary outcome
Number of Subjects With Medically Defined Endoscopic Response
Time frame: Week 12
Defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.
3 secondary outcomes
Induction of Clinical Remission
Time frame: Week 12
Change in Amount of Concomitant Medications
Time frame: Week 12
Proportion of Subjects in Endoscopic Remission
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gil Y Melmed, MD principal investigator
Cedars-Sinai Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Posaconazole Delayed Release Oral Tablet in people with Crohn Disease and CARD9 S12N Risk Allele, run by Cedars-Sinai Medical Center at 2 sites in United States.
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 9 inclusion and 11 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: stopped early, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Medically Defined Endoscopic Response (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Feb 2026.