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

NCT05049525 | Terminated Phase 2

• 1 other identifier: MHICC-2019-001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Crohn's Disease; Inflammatory Bowel Diseases

Keywords

Endoscopy; Radiology; Itraconazole; Terbinafine; Chronic Inflammatory Disorder; Malassezia Restricta

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on clinical remission assessed by the HBI.

  20 Weeks

• 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).

  20 Weeks

• To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on fecal and serologic markers.

  20 Weeks

• 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).

  20 weeks

Other Outcomes (2)

• 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.

  28 Weeks

• To evaluate steroid use between active and placebo groups at study completion.

  28 Weeks

Study Arms (2)

Itraconazole and Terbinafine

ACTIVE COMPARATOR

During the first 4 weeks itraconazole will be administered alone at 200 mg twice daily, followed by itraconazole 200 mg twice daily and terbinafine 250 mg twice daily for the remaining 16 weeks. Both drugs will be administered orally.

Drug: Itraconazole 400 mg/day and terbinafine 500 mg/day administered orally.

Placebo

PLACEBO COMPARATOR

During the first 4 weeks a placebo will be administered alone at 200 mg twice daily, followed by placebo 200 mg twice daily and another placebo 250 mg twice daily for the remaining 16 weeks. Both placebos will be administered orally.

Drug: Itraconazole's matching placebo 400 mg/day and terbinafine's matching placebo 500 mg/day administered orally.

Interventions

Itraconazole 400 mg/day and terbinafine 500 mg/day administered orally. DRUG

Itraconazole capsules of 100 mg, antifungal agent. Terbinafine tablets 250 mg (as terbinafine hydrochloride), antifungal agent.

Itraconazole and Terbinafine

Itraconazole's matching placebo 400 mg/day and terbinafine's matching placebo 500 mg/day administered orally. DRUG

Matching placebo of itraconazole capsules of 100 mg, antifungal agent. Matching placebo of terbinafine tablets 250 mg, antifungal agent.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Montreal Heart Institute: lead

Study Sites (4)

CIUSSS de l'Est-de-l'Île-de-Montréal, Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)

Montreal, Quebec, H2X0A9, Canada

Location

McGill University Health Center

Montreal, Quebec, H3G1A4, Canada

Location

Centre intégré universitaire de santé et de services sociaux de l'Estrie - CHUS

Sherbrooke, Quebec, J1G 2E8, Canada

Location

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

Itraconazole; Terbinafine

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Jean-Claude Tardif, MD

  Montreal Heart Institute (MHI)

  PRINCIPAL INVESTIGATOR

• Edmond-Jean Bernard, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 20, 2021
• Study Start: February 22, 2022
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2024
• Last Updated: May 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)