Evaluation of the Response of Itraconazole and Terbinafine Therapy in Subjects With Crohn's Disease

Crohn's Disease Clinical Trial

— CD-IT  

Official title:

Evaluation of the Response of Itraconazole and Terbinafine Therapy in Subjects With Crohn's Disease Not Responding Adequately to Current Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05049525
• Other study ID #: MHICC-2019-001
• Status: Terminated
• Phase: Phase 2
• Start date: February 22, 2022
• Est. completion date: February 28, 2024

Study information

• Verified date: May 2024
• Source: Montreal Heart Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the response of itraconazole and terbinafine therapy compared to placebo in patients with mild to moderate Crohn's disease (CD).

Description:

This multicenter, randomized, double-blind, placebocontrolled, phase II, proof of concept study will randomize 68 subjects at 2 to 5 clinical sites in Canada. Following signature of informed consent, subjects who meet entry criteria will be randomized in a 1:1 ratio to receive either itraconazole and terbinafine, or matching placebos. During the first 4 weeks subjects will receive itraconazole 200 mg twice daily or matching placebo, followed by itraconazole 200 mg twice daily and terbinafine 250 mg twice daily or matching placebos for the remaining 16 weeks. The 2 drugs will be administered orally.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: February 28, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subjects with endoscopy/radiology confirmation of active disease within 6 months prior to enrolment;
• Mild to moderate active CD defined by the HBI score of = 5 to = 16 at baseline;
• Female of childbearing potential must have a negative urine pregnancy test at screening and at randomization baseline Visit 2. Women are considered not of

childbearing potential if they either:

• Have had a hysterectomy or tubal ligation prior to baseline visit or;
• Are postmenopausal defined as no menses for 12 months or a FSH level (if available) in the menopausal range.
• Women of childbearing potential must agree to use an effective double method of birth control throughout the study: barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, and diaphragm) in combination with other methods of contraception including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, abstinence, or a sterile sexual partner.
• Subjects with the capacity to provide informed consent.

Exclusion Criteria:

• Subject with a current diagnosis of ulcerative colitis (UC);
• Contraindication to the use of itraconazole including congestive heart failure, ventricular dysfunction, ventricular arrhythmia, or negative inotropic state;
• Subjects with elevated or abnormal liver enzymes (ALT/AST>3 ULN) or patients with pre-existing chronic or active liver disease at screening;
• Female subject who is pregnant, planning to become pregnant during the study, or breastfeeding;
• Subject with renal impairment (creatinine clearance = 50 mL/min using Cockcroft-Gault equation);
• Subject with a known hypersensitivity to itraconazole, terbinafine, or any of their excipients;
• Subjects on medications which interact with itraconazole: methadone, pimozide, quinidine or other CYP3A4 inhibitors;
• Positive C. difficile toxin test at screening;
• Use of steroid greater than 20 mg/day;
• Change of steroid dosage in the 2 weeks prior to enrolment;
• Change in CD therapy:
• The Anti-TNFs, anti-integrins, anti-IL12/23 in the 4 months prior to enrolment;
• Thiopurines or methotrexate (MTX), in the 2 months prior to enrolment;
• Participation in other clinical trial within 30 days of signing the Information and Consent Form (ICF).

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Inflammatory Bowel Diseases

Intervention

Drug:
• Itraconazole 400 mg/day and terbinafine 500 mg/day administered orally.
Itraconazole capsules of 100 mg, antifungal agent. Terbinafine tablets 250 mg (as terbinafine hydrochloride), antifungal agent.
• Itraconazole's matching placebo 400 mg/day and terbinafine's matching placebo 500 mg/day administered orally.
Matching placebo of itraconazole capsules of 100 mg, antifungal agent. Matching placebo of terbinafine tablets 250 mg, antifungal agent.

Locations

Country	Name	City	State
Canada	Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)	Montréal	Quebec
Canada	CIUSSS de l'Est-de-l'Île-de-Montréal, Hôpital Maisonneuve-Rosemont	Montréal	Quebec
Canada	McGill University Health Center	Montréal	Quebec
Canada	Centre intégré universitaire de santé et de services sociaux de l'Estrie - CHUS	Sherbrooke	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Montreal Heart Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory analyses using genetic data (pharmacogenomic and metagenomics) as well as microbiotic testing will be described at a later time point and in a separate document.	To determine the link between genetics and the response to therapy and inflammation. The microbiote genes will also be evaluated.	28 Weeks
Other	To evaluate steroid use between active and placebo groups at study completion.	Steroid Use in Subjects with Crohn's Disease will be reported as the proportion of subjects who's steroid use was decreased. increased, changed or stopped.	28 Weeks
Primary	To evaluate the response of itraconazole and terbinafine therapy compared to placebo in subjects with CD, assessed by the Modified Harvey Bradshaw Index (HBI).	Clinical response defined as a decrease from baseline to end of treatment in HBI = 3 points	20 Weeks
Secondary	To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on clinical remission assessed by the HBI.	Persistence of clinical response defined as a decrease from baseline to 8 weeks post end of treatment in HBI = 3 points; Clinical remission defined as an HBI at end of treatment = 4 points; Persistence of clinical remission defined as an HBI at 8 weeks post end of treatment = 4 points; Change from baseline to end of treatment in HBI	20 Weeks
Secondary	To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on endoscopic response assessed by the Simplified Endoscopic Score for Crohn's disease (SES-CD).	Endoscopic response defined a decrease from baseline to end of treatment in SES-CD = 50% of the baseline SES-CD; Change from baseline to end of treatment in SES-CD	20 Weeks
Secondary	To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on fecal and serologic markers.	Change from baseline to end of treatment in FC levels; Change from baseline to end of treatment in CRP levels	20 Weeks
Secondary	To evaluate the effect of study treatment on the primary endpoint in the subgroup of patients with positive ASCA (as measured on frozen plasma samples at end of the study).	Change from baseline to end of treatment in ASCA levels; Change from baseline to 8 weeks post end of treatment in ASCA levels	20 weeks