Pilot Study of Posaconazole in Crohn's Disease

NCT ID: NCT04966585

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-17
• Study Completion Date: 2025-01-22

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Posaconazole

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

Group Type: EXPERIMENTAL

Posaconazole Delayed Release Oral Tablet

Intervention Type: 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.

Placebo

Subjects administered three matching placebo tablets twice daily for 1 day followed by three tablets daily for 12 weeks

Group Type: PLACEBO_COMPARATOR

Matching Placebo Tablet

Intervention Type: 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.

Interventions

Posaconazole Delayed Release Oral Tablet

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.

Intervention Type: DRUG

Matching Placebo Tablet

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.

Intervention Type: DRUG

Other Intervention Names

Noxafil

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Gil Melmed

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gil Y Melmed, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center (CSMC)

Los Angeles, California, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01DK125495-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MOD03104

Identifier Type: -

Identifier Source: org_study_id