Pilot Study of Posaconazole in Crohn's Disease

NCT04966585 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: MOD031041R01DK125495-01A1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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. 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

Keywords

Crohn's; Malassezia; CARD9 S12N; Antifungal

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 12

Secondary Outcomes (3)

• Induction of Clinical Remission

  Week 12

• Change in Amount of Concomitant Medications

  Week 12

• Proportion of Subjects in Endoscopic Remission

  Week 12

Study Arms (2)

Posaconazole

EXPERIMENTAL

Subjects administered posaconazole (Noxafil®, Merck) 300mg twice daily for 1 day followed by 300mg daily for 12 weeks

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

Drug: Matching Placebo Tablet

Interventions

Posaconazole Delayed Release Oral Tablet DRUG

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.

Also known as: Noxafil

Posaconazole

Matching Placebo Tablet DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Cedars-Sinai Medical Center (CSMC)

Los Angeles, California, 90048, United States

Location

Mayo Clinic

Rochester, Minnesota, 55901, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

posaconazole

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Gil Y. Melmed, MD
• Organization: Cedars-Sinai

gil.melmed@cshs.org

310-423-4100

Study Officials

• Gil Y Melmed, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Both subject and clinical staff will be masked to treatment group assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects will be randomly assigned to receive posaconazole or placebo in 1:1 fashion.

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: August 17, 2022
• Primary Completion: January 22, 2025
• Study Completion: January 22, 2025
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)