search
Back to results

CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis (CAMB)

Primary Purpose

Candidiasis, Chronic Mucocutaneous

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Amphotericin B
Sponsored by
Matinas BioPharma Nanotechnologies, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Candidiasis, Chronic Mucocutaneous focused on measuring 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)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Institute of Allergy and Infectious Disease (NIAID)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAMB (Encochleated Amphotericin B)

Arm Description

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

Outcomes

Primary Outcome Measures

Symptoms of mucocutaneous candidiasis
dysphagia, odynophagia, retrosternal pain, oral pain, burning of mouth or vaginal erythema, vulvovaginal pruritus, vaginal discharge

Secondary Outcome Measures

Area under the plasma concentration versus time curve (AUC)
Drug concentrations in plasma, urine and saliva
Peak Plasma Concentration (Cmax)
Adverse events, changes in laboratory parameters

Full Information

First Posted
November 16, 2015
Last Updated
August 17, 2022
Sponsor
Matinas BioPharma Nanotechnologies, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02629419
Brief Title
CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis
Acronym
CAMB
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
November 9, 2021 (Actual)
Study Completion Date
August 6, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Matinas BioPharma Nanotechnologies, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CAMB (Encochleated Amphotericin B)
Arm Type
Experimental
Arm Description
Encochleated Amphotericin B (200 mg, 400 mg, 800 mg)
Intervention Type
Drug
Intervention Name(s)
Amphotericin B
Other Intervention Name(s)
Encochleated Amphotericin B, CAMB, MAT2203
Intervention Description
Lipid crystal nano-particle formulation of amphotericin B
Primary Outcome Measure Information:
Title
Symptoms of mucocutaneous candidiasis
Description
dysphagia, odynophagia, retrosternal pain, oral pain, burning of mouth or vaginal erythema, vulvovaginal pruritus, vaginal discharge
Time Frame
14-days at highest titrated dose
Secondary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC)
Description
Drug concentrations in plasma, urine and saliva
Time Frame
Single and Multiple Dose (14-days)
Title
Peak Plasma Concentration (Cmax)
Time Frame
Single and Multiple Dose (14-days)
Title
Adverse events, changes in laboratory parameters
Time Frame
up to 54 days
Other Pre-specified Outcome Measures:
Title
Long-term adverse events, changes in laboratory parameters
Time Frame
up to 6-months
Title
Long-term symptoms of mucocutaneous candidiasis
Description
dysphagia, odynophagia, retrosternal pain, oral pain, burning of mouth or vaginal erythema, vulvovaginal pruritus, vaginal discharge
Time Frame
up to 6-months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandra Freeman, MD
Organizational Affiliation
National Institute of Allergy and Infectious Diseases (NIAID)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institute of Allergy and Infectious Disease (NIAID)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35699443
Citation
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.
Results Reference
derived

Learn more about this trial

CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis

We'll reach out to this number within 24 hrs