CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis

Study Overview
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Brief Summary
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This is an open-label, dose-titration trial to study the efficacy, safety, and pharmacokinetics of oral cochleate amphotericin B (CAMB) in the treatment of mucocutaneous candidiasis infections in patients who are refractory or intolerant to standard non intravenous therapies.

Detailed Description
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Patients aged 18 to 75 years with mucocutaneous candidiasis (esophageal, oropharyngeal, or vulvovaginal) who are refractory or intolerant to standard non-intravenous therapies will be enrolled. Patients will initially be treated in a short-term dose titration period, where the dose may be increased in patients that do not respond clinically. Patients who do not respond clinically to the highest dose of drug will discontinue the protocol. Patients that respond to treatment and tolerate the study medication will be eligible to enter a long-term extension (up to 36-months).

Official Title
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A Phase 2a Efficacy, Safety, Tolerability, and PK Study of Encochleated Amphotericin B (CAMB/MAT2203) in Patients With Mucocutaneous Candidiasis Who Are Refractory or Intolerant to Standard Non-Intravenous Therapies

Conditions
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Candidiasis, Chronic Mucocutaneous

Intervention / Treatment
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* Drug: Amphotericin B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a clinical diagnosis of at least one of the following: Persistent OPC for greater than 2 weeks documented on at least one occasion by KOH or fungal stain and confirmed by mycological culture to be azole resistant within the previous 6 months and/or intolerance to standard non intravenous therapies. EC associated with clinical symptoms of retrosternal pain, odynophagia, and/or pain with swallowing and documented by esophageal biopsy or visualization with culture documenting azole resistance within the previous 6 months and/or intolerance to standard non-intravenous therapies. Persistent VVC for greater than 2 weeks as documented by presence of vaginal symptoms and a positive wet mount showing Candida structures and confirmed by a vaginal culture positive for Candida with azole resistance within the previous 6 months and/or intolerance to standard non intravenous therapies. Patient is expected to survive for > = 6 months. Willing to have samples stored for future research. Agree to use highly effective contraception. Contraception: Because the effects of CAMB on the developing human fetus are unknown, sexually active patients of childbearing potential must agree to use highly effective contraception as outlined below before study entry and for the duration of study participation. Females of childbearing potential must have a negative pregnancy test result before receiving CAMB. During the course of the study, if a patient becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are: Intrauterine device (IUD) or equivalent. Hormonal contraceptives (eg, consistent, timely and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the patient uses contraceptive pill, patch, or ring, then a barrier method (eg, male/female condom, cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity. Be in a stable, long-term monogamous relationship, per PI assessment, with a partner that does not pose any potential pregnancy risk, eg, has undergone a vasectomy at least 6 months prior to first dose of study agent or is of the same sex as the patient. Have had a hysterectomy and/or a bilateral tubal ligation or both ovaries removed. Exclusion Criteria: Allergy to any AMB product or any component of CAMB (eg, phosphatidylserine) Have evidence of systemic fungal infections requiring intravenous antifungal therapy Pregnant or nursing women, and women intending to become pregnant during the study period Had a concomitant medical condition that could interfere with study drug evaluation or that is a contraindication to the proposed investigational treatment based upon known agent safety profile or toxicities. Had any of the following laboratory abnormalities at the screening visit: Alanine Transaminase (ALT), Aspartate Transaminase (AST) and Alkaline phosphatase (ALP) > 2.5 times the upper limit of normal (ULN). Total bilirubin level > 2.5 times the ULN Serum creatinine level > 2 times the ULN Absolute neutrophil count less than 500 cells/microliter Potassium level less than or equal to 3.5 mmol/L Exposure to any investigational agent within 4 weeks prior to Day 0 (Baseline). Current or recent history (past 12 months) of drug or alcohol abuse. Use of intravenous AMB products within 1-week of start of study drug administration Use of non-intravenous AMB products (such as oral AMB swishes) within 72 hours prior to start of study drug administration Subjects receiving potassium supplements. Any other condition the investigator believes would interfere with the patient s ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAMB (Encochleated Amphotericin B)<br>Encochleated Amphotericin B (200 mg, 400 mg, 800 mg) | Drug: Amphotericin B<br>* Lipid crystal nano-particle formulation of amphotericin B<br>* Other names: MAT2203;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms of mucocutaneous candidiasis | dysphagia, odynophagia, retrosternal pain, oral pain, burning of mouth or vaginal erythema, vulvovaginal pruritus, vaginal discharge | 14-days at highest titrated dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | Drug concentrations in plasma, urine and saliva | Single and Multiple Dose (14-days) | 
| Peak Plasma Concentration (Cmax) |  | Single and Multiple Dose (14-days) | 
| Adverse events, changes in laboratory parameters |  | up to 54 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STAT3 deficient Hyper IgE syndrome, Gain of function STAT1 defects, Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), IL-17/IL-22 autoantibodies from thymoma, Job's Syndrome (Hyperimmunoglobulin E Syndrome, Buckley Syndrome)