CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis

NCT02629419 | Completed Phase 2 Results DMC

• 2 other identifiers: MB-7000416-I-0002
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Candidiasis, Chronic Mucocutaneous

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• Clinical Response to Treatment of Mucocutaneous Candidiasis

  Number of subjects with a clinical response of clinical cure or improvement. Clinical cure was defined as absence of signs or symptoms of infection. Clinical improvement was defined as follows: * OPC or EC: partial resolution defined as greater than or equal to 50% of Baseline signs or symptoms * VVC: reduction of greater than or equal to 50% of clinical severity score from Baseline Severity of each symptom was graded on a scale from zero (absence of symptoms) to 3 (severe symptoms). The sum of all scores for all symptoms was used as the clinical severity score. Higher scores mean worse outcomes.

  14-days at highest titrated dose

Secondary Outcomes (4)

• Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Postdose

  Single and Multiple Doses (14-days)

• Maximum Plasma Concentration (Cmax)

  Single and Multiple Doses (14-days)

• Time to Reach Maximum Plasma Concentration (Tmax)

  Single and Multiple Doses (14-days)

• Long-term Adverse Events, Changes in Laboratory Parameters

  up to 60 months

Study Arms (1)

CAMB (Encochleated Amphotericin B)

EXPERIMENTAL

Encochleated Amphotericin B (200 mg, 400 mg, 800 mg)

Drug: Amphotericin B

Interventions

Amphotericin B DRUG

Oral lipid nanocrystal formulation of amphotericin B

Also known as: Encochleated Amphotericin B, CAMB, MAT2203

CAMB (Encochleated Amphotericin B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a clinical diagnosis of at least one of the following:
• Persistent oropharyngeal candidiasis (OPC) for greater than or equal to 5 days documented on at least one occasion by potassium hydroxide (KOH) test 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 or lack of improvement or worsening of OPC after receipt of appropriately dosed oral azole therapy.
• Esophageal candidiasis (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 or lack of improvement or worsening of EC after appropriately dosed azole therapy.
• Persistent vulvovaginal candidiasis (VVC) for greater than or equal to 5 days 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 or lack of improvement or worsening of VVC after appropriately dosed azole therapy.
• Patient is expected to survive for greater than or equal to 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 principal investigator (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.

You may not qualify if:

• Allergy to any amphotericin B (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 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
• 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.

Sponsors & Collaborators

• Matinas BioPharma Nanotechnologies, Inc.: lead

Study Sites (1)

National Institute of Allergy and Infectious Disease (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Desai JV, Urban A, Swaim DZ, Colton B, Kibathi LW, Ferre EMN, Stratton P, Merideth MA, Hunsberger S, Matkovits T, Mannino R, Holland SM, Tramont E, Lionakis MS, Freeman AF. Efficacy of Cochleated Amphotericin B in Mouse and Human Mucocutaneous Candidiasis. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0030822. doi: 10.1128/aac.00308-22. Epub 2022 Jun 14.

  PMID: 35699443 DERIVED

MeSH Terms

Conditions

Candidiasis, Chronic Mucocutaneous; Polyendocrinopathies, Autoimmune; Job Syndrome

Interventions

Amphotericin B

Condition Hierarchy (Ancestors)

Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Dermatomycoses; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

Did not reach target number of participants (small sample size). All participants were female and Caucasian.

Results Point of Contact

• Title: Theresa Matkovits, PhD
• Organization: Matinas BioPharma

tmatkovits@matinasbiopharma.com

862-812-1436

Study Officials

• Alexandra Freeman, MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: December 14, 2015
• Study Start: September 27, 2016
• Primary Completion: November 9, 2021
• Study Completion: August 6, 2022
• Last Updated: August 7, 2024
• Results First Posted: June 7, 2024

Record last verified: 2024-07

Locations

US (1)