Posaconazole in Genetically Defined Patients with CD

What is the Purpose of this Study?

This study focuses on individuals who have been diagnosed with Crohn's disease and are at risk for fungal infection based on genetic determination. The purpose of the study is to evaluate the effects of oral posaconazole for the treatment of active Crohn's disease in a genetically defined population. Posaconazole is approved by the U.S. Food and Drug Administration (FDA) for the treatment of fungal infections, but its use in this study is experimental. The main procedures of the study include physical exams, laboratory tests, colonoscopy with biopsies, EKG, chest X-rays, questionnaires, and a daily diary. Participants will be randomly assigned to one of two groups: one group will receive the treatment (posaconazole), and the other will receive placebo (inactive substance). Samples will also be obtained throughout the study for biomarker testing. A biomarker is a biological molecule found in blood, other body fluids, or tissues that may be a sign of a condition or disease; biomarkers are good indicators of treatment response.

Eligibility

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

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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Multicenter Randomized, Double-Blinded, Placebo-Controlled Study of Posaconazole in Genetically-Defined Patients with Active Crohn's Disease.

Study Details

Disease Type/Condition

Inflammatory Bowel Disease

Principal Investigator

Melmed, Gil

Co-Investigators

David Underhill

Age Group

Adult

Phase

I/II

IRB Number

STUDY00000256

ClinicalTrials.gov ID

NCT04966585

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org