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Study to Assess Amphotericin B Cystetic for Inhalation (ABCI) Doses in Healthy Volunteers & People With Cystic Fibrosis (ABCI)

Primary Purpose

Cystic Fibrosis

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ABCI
Placebo
Sponsored by
Cystetic Medicines, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Part A and Part B: Each subject must meet the following criteria to be enrolled in Part A and Part B of this study. Subject has signed, dated, and received a copy of the IRB/IEC-approved written ICF. Subject is male or female aged ≥18 to ≤55 years. Subject has a BMI between 18 and 32 kg/m2 Subject has an FEV1 of >90% of predicted normal value Subject has normal or clinically acceptable physical examination, vital signs, clinical laboratory values, and ECG at Screening. Female subjects must be of non-childbearing potential or male/female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures Part C: Each subject must meet the following criteria to be enrolled in Part C of this study. Subject has signed, dated, and received a copy of the IRB/IEC-approved written ICF. Age 16 years or older Confirmed diagnosis of CF, including sweat chloride >60 mM. Subject is either: Being treated with an approved CFTR modulator for at least 28 days prior to Screening, or Not being treated with a CFTR modulator FEV1 ≥40% and ≤90% of predicted normal value Stable CF disease and treatment regiment Female subjects must be of non-childbearing potential or male/female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures Exclusion Criteria: Part A and Part B: Any subject who meets any of these criteria must be excluded from Part A and Part B of this study: Subject has history or evidence of any clinically significant pulmonary condition Subject has history or evidence of any clinically significant diseases or conditions Subject has history of malignancy of any type Subject has an active COVID-19 infection within 4 weeks Subject is positive for human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies, or has a positive QuantiFERON®-tuberculosis Gold (QFT-G) test for tuberculosis at Screening Subject has a self-reported lower respiratory tract infection within 6 weeks Subject has evidence of any active or suspected bacterial, viral, fungal or parasitic infections within the past 4 weeks A subject who is an active smoker or a former smoker Subject has history of alcohol or drug abuse in the past year Subject has tested positive for drugs (including cannabis), nicotine/cotinine, and/or alcohol use at Screening, subject has consumed alcohol within 24 hours prior to Visit 3 Subject has participated in any clinical study or had been treated with any investigational drugs within 28 days or 5 half-lives Female subject who is pregnant or breastfeeding. Subject has any episode of paradoxical bronchospasm in the past 12 months. Subject has pacemaker; is not in sinus rhythm; has a corrected QT interval (QTc; using Fridericia's [QTcF] formula) of >450 ms (for males) and >470 ms (for females); or has a left bundle branch block or bifascicular block. Subject has a pulse <40 or >100 bpm; systolic blood pressure >140 mmHg, or diastolic blood pressure >90 mmHg at Screening Subject has Type I or II diabetes requiring medication. Subject has received any vaccine within 30 days prior to Day 1. Subject has received any of the following immunosuppressant therapies within 6 months prior to Screening: imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, or methotrexate. Subject has received any antibody or therapeutic biologic product during the 6 months prior to Screening. Subject has received any oral, intravenous, or intramuscular steroid within 4 weeks prior to Screening. Intrathecal or intraarticular steroids are permitted. A subject who is not vaccinated with the COVID-19 vaccine with appropriate window from last dose of vaccine to Screening per local guidelines, policies, and availability within 30 days prior to Day 1. Part C: Any subject who meets any of these criteria must be excluded from Part C of this study: History of any illness or any clinical condition that might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. Any of the following abnormal laboratory tests: Hemoglobin, Total bilirubin, liver enzymes or creatine clearance An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for sinopulmonary disease within 28 days before the screening visit. An acute illness not related to CF within 14 days before the first dose of study drug. Subject has an active COVID-19 infection within 4 weeks prior to screening. Ongoing or prior participation in a study of an investigational treatment within 28 days or 5 terminal half-lives (whichever is longer) before screening. Female subject who is pregnant or breastfeeding. Please refer to study protocol for the complete inclusion/exclusion criteria list.

Sites / Locations

  • Monash Medical CentreRecruiting
  • New Zealand Clinical ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part A Healthy Volunteer

Part B Healthy Volunteer

Part C People with Cystic Fibrosis

Arm Description

Subjects will be assigned to one of six planned dose cohorts and receive single doses of ABCI (0.5mg, 1.0mg, 2.0mg, 4.0mg, 6.0mg, 10.0mg). In each cohort, six subjects will receive ABCI and 2 will receive placebo

Subjects will be assigned to one of three planned dose cohorts and receive a loading dose and multiple ascending doses of ABCI (loading dose 1.5mg/0.5mg daily, loading dose 6.0mg/2.0 daily, loading dose 10.0mg/4.0mg daily). In each cohort, six subjects will receive ABCI and 2 will receive placebo.

Subjects will be assigned to one of two planned dose cohorts of ABCI (loading dose 6.0mg/2.0mg daily, loading dose 10.0mg/4.0mg daily) for a total of 28 days of open-label study drug administration. Up to 12 subjects with CF, 6 subjects on cystic fibrosis transmembrane conductance regulator (CFTR) modulators and 6 subjects not on CFTR modulators.

Outcomes

Primary Outcome Measures

Adverse Events (AEs), and Serious Adverse Events (SAEs)
The safety and tolerability of ABCI following oral inhalation of single and multiple ascending doses in healthy subjects (Parts A and B), and in people with Cystic Fibrosis (Part C) will be assessed

Secondary Outcome Measures

Pharmacokinetics (PK) Profile - SAD Cmax
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
Pharmacokinetics (PK) Profile - SAD Tmax
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
Pharmacokinetics (PK) Profile - SAD AUC0-24
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
Pharmacokinetics (PK) Profile - SAD AUClast
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
Pharmacokinetics (PK) Profile - SAD AUCinf
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf)
Pharmacokinetics (PK) Profile - SAD AUCtau
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration- concentration-time curve over the dosing interval (AUCtau)
Pharmacokinetics (PK) Profile - MAD Cmax
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
Pharmacokinetics (PK) Profile - MAD Tmax
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
Pharmacokinetics (PK) Profile - MAD AUC0-24
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
Pharmacokinetics (PK) Profile - MAD Plasma AmB trough assessments
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB trough assessments
Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: AmB concentrations in BAL fluid after study drug administration
AmB concentrations - Subjects with CF
Cumulative effect on pre-dose AmB concentrations through Day 29 and assessment of washout through Day 42

Full Information

First Posted
February 28, 2023
Last Updated
September 26, 2023
Sponsor
Cystetic Medicines, Inc.
Collaborators
DevPro Biopharma
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1. Study Identification

Unique Protocol Identification Number
NCT05802264
Brief Title
Study to Assess Amphotericin B Cystetic for Inhalation (ABCI) Doses in Healthy Volunteers & People With Cystic Fibrosis
Acronym
ABCI
Official Title
A 3-part Study of ABCI: A Randomized, Double-blind, Placebo-controlled, Single-ascending Dose Phase 1a Study in Healthy Volunteers (Part A), a Randomized, Double-blind, Placebo-controlled, 14- and 28-day Multiple-ascending Dose Phase 1a Study in Healthy Volunteers (Part B), and a 28-day Open-Label Phase 1b Study in Subjects With Cystic Fibrosis (Part C)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cystetic Medicines, Inc.
Collaborators
DevPro Biopharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a 3-part, single-ascending dose Phase 1a randomized, double-blind, placebo-controlled study in healthy volunteers (Part A) and multiple-ascending dose Phase 1a randomized, double-blind, placebo-controlled study in healthy volunteers (Part B), and a Phase 1b open-label study in subjects with CF (Part C) to assess the safety, tolerability, PK, and preliminary efficacy of ABCI. Subjects will be evaluated for eligibility during Screening within 30 days prior to Day 1 (Randomization; Visit 3). In Parts A and B, eligible healthy volunteers may be enrolled in the study and randomly allocated to treatment with ABCI or placebo as described below. In Part C, eligible subjects with CF may be enrolled in the study and receive treatment with ABCI as described below. Approximately 72 healthy subjects total will be randomized to 9 cohorts (48 subjects in 6 cohorts in Part A, 24 subjects in 3 cohorts in Part B) and up to 12 subjects with CF will receive the medium dose (2 sentinel subjects) or high dose (up to 10 subjects) of ABCI in Part C.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A Healthy Volunteer
Arm Type
Experimental
Arm Description
Subjects will be assigned to one of six planned dose cohorts and receive single doses of ABCI (0.5mg, 1.0mg, 2.0mg, 4.0mg, 6.0mg, 10.0mg). In each cohort, six subjects will receive ABCI and 2 will receive placebo
Arm Title
Part B Healthy Volunteer
Arm Type
Experimental
Arm Description
Subjects will be assigned to one of three planned dose cohorts and receive a loading dose and multiple ascending doses of ABCI (loading dose 1.5mg/0.5mg daily, loading dose 6.0mg/2.0 daily, loading dose 10.0mg/4.0mg daily). In each cohort, six subjects will receive ABCI and 2 will receive placebo.
Arm Title
Part C People with Cystic Fibrosis
Arm Type
Experimental
Arm Description
Subjects will be assigned to one of two planned dose cohorts of ABCI (loading dose 6.0mg/2.0mg daily, loading dose 10.0mg/4.0mg daily) for a total of 28 days of open-label study drug administration. Up to 12 subjects with CF, 6 subjects on cystic fibrosis transmembrane conductance regulator (CFTR) modulators and 6 subjects not on CFTR modulators.
Intervention Type
Combination Product
Intervention Name(s)
ABCI
Other Intervention Name(s)
Amphotericin B Cystetic for Inhalation
Intervention Description
Subjects will receive ABCI via oral inhalation
Intervention Type
Combination Product
Intervention Name(s)
Placebo
Intervention Description
Subjects will receive ABCI via oral inhalation
Primary Outcome Measure Information:
Title
Adverse Events (AEs), and Serious Adverse Events (SAEs)
Description
The safety and tolerability of ABCI following oral inhalation of single and multiple ascending doses in healthy subjects (Parts A and B), and in people with Cystic Fibrosis (Part C) will be assessed
Time Frame
up to 10 weeks
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) Profile - SAD Cmax
Description
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
Time Frame
1 day
Title
Pharmacokinetics (PK) Profile - SAD Tmax
Description
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
Time Frame
1 day
Title
Pharmacokinetics (PK) Profile - SAD AUC0-24
Description
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
Time Frame
1 day
Title
Pharmacokinetics (PK) Profile - SAD AUClast
Description
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
Time Frame
1 day
Title
Pharmacokinetics (PK) Profile - SAD AUCinf
Description
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf)
Time Frame
1 day
Title
Pharmacokinetics (PK) Profile - SAD AUCtau
Description
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration- concentration-time curve over the dosing interval (AUCtau)
Time Frame
Up to 28 days
Title
Pharmacokinetics (PK) Profile - MAD Cmax
Description
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
Time Frame
Up to 28 days
Title
Pharmacokinetics (PK) Profile - MAD Tmax
Description
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
Time Frame
Up to 28 days
Title
Pharmacokinetics (PK) Profile - MAD AUC0-24
Description
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
Time Frame
Up to 28 days
Title
Pharmacokinetics (PK) Profile - MAD Plasma AmB trough assessments
Description
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB trough assessments
Time Frame
Up to 84 days
Title
Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid
Description
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: AmB concentrations in BAL fluid after study drug administration
Time Frame
Up to 29 days
Title
AmB concentrations - Subjects with CF
Description
Cumulative effect on pre-dose AmB concentrations through Day 29 and assessment of washout through Day 42
Time Frame
Through 42 days
Other Pre-specified Outcome Measures:
Title
ppFEV1 - Subjects with CF
Description
Absolute change in percent-predicted morning pre-dose forced expiratory volume in 1 second (ppFEV1) from baseline to Day 29 and from Day 29 to Day 42
Time Frame
Up to 42 days
Title
LCI - Subjects with CF
Description
Absolute change in Lung Clearance Index (LCI) (where available)
Time Frame
Up to 42 days
Title
Questionnaire - Subjects with CF
Description
Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ-R) in Subjects with Cystic Fibrosis: Revised (CFQ-R) respiratory domain score from baseline to Day 29 and to Day 42 where scores range from 0 to 100, with higher scores indicating better health.
Time Frame
Up to 42 days
Title
ppFVC - Subjects with CF
Description
Absolute change in percent-predicted morning pre-dose forced vital capacity (ppFVC) from baseline to Day 29 and from Day 29 to Day 42
Time Frame
Up to 42 days
Title
FVC - Subjects with CF
Description
Absolute change in morning pre-dose FVC from baseline to Day 29 and from Day 29 to Day 42 (mLs)
Time Frame
Up to 42 days
Title
FEV1 - Subjects with CF
Description
Absolute change in morning pre-dose FEV1 from baseline to Day 29 and from Day 29 to Day 42 (mLs)
Time Frame
Up to 42 days
Title
DLCO - Subjects with CF
Description
Absolute change in diffusing capacity of the lungs for carbon monoxide (DLCO [expressed as percent-predicted corrected for hemoglobin]) from baseline to Day 29
Time Frame
Up to 29 days
Title
Body weight - Subjects with CF
Description
Absolute change in body weight from baseline to Day 29 and from Day 29 to Day 42
Time Frame
Up to 42 days
Title
FRI biomarkers - Subjects with CF
Description
Change from baseline in Functional Respiratory Imaging (FRI) biomarkers, including but not limited to airway wall volume, mucus plug volume, and blood vessel volume (where available)
Time Frame
Up to 28 days
Title
IVIVC - chloride secretion - Subjects with CF
Description
Change in chloride secretion in response to AmB in vitro in primary cultured nasal epithelial cells
Time Frame
Up to 42 days
Title
IVIVC - FEV1 - Subjects with CF
Description
Comparison of change from baseline FEV1 (ppFEV1 and absolute FEV1) (Day 29) and change in chloride secretion in response to AmB in vitro in primary cultured nasal epithelial cells
Time Frame
Up to 42 days
Title
IVIVC - ASL pH - Subjects with CF
Description
Change in ASL pH in response to AmB in vitro in primary cultured nasal epithelial cells
Time Frame
Up to 42 days
Title
IVIVC - FEV1 & ASL pH - Subjects with CF
Description
Comparison of change from baseline FEV1 (ppFEV1 and absolute FEV1) (Day 29) and ASL pH in response to AmB in vitro in primary cultured nasal epithelial cells
Time Frame
Up to 29 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Part A and Part B: Each subject must meet the following criteria to be enrolled in Part A and Part B of this study. Subject has signed, dated, and received a copy of the IRB/IEC-approved written ICF. Subject is male or female aged ≥18 to ≤55 years. Subject has a BMI between 18 and 32 kg/m2 Subject has an FEV1 of >90% of predicted normal value Subject has normal or clinically acceptable physical examination, vital signs, clinical laboratory values, and ECG at Screening. Female subjects must be of non-childbearing potential or male/female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures Part C: Each subject must meet the following criteria to be enrolled in Part C of this study. Subject has signed, dated, and received a copy of the IRB/IEC-approved written ICF. Age 16 years or older Confirmed diagnosis of CF, including sweat chloride >60 mM. Subject is either: Being treated with an approved CFTR modulator for at least 28 days prior to Screening, or Not being treated with a CFTR modulator FEV1 ≥40% and ≤90% of predicted normal value Stable CF disease and treatment regiment Female subjects must be of non-childbearing potential or male/female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures Exclusion Criteria: Part A and Part B: Any subject who meets any of these criteria must be excluded from Part A and Part B of this study: Subject has history or evidence of any clinically significant pulmonary condition Subject has history or evidence of any clinically significant diseases or conditions Subject has history of malignancy of any type Subject has an active COVID-19 infection within 4 weeks Subject is positive for human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies, or has a positive QuantiFERON®-tuberculosis Gold (QFT-G) test for tuberculosis at Screening Subject has a self-reported lower respiratory tract infection within 6 weeks Subject has evidence of any active or suspected bacterial, viral, fungal or parasitic infections within the past 4 weeks A subject who is an active smoker or a former smoker Subject has history of alcohol or drug abuse in the past year Subject has tested positive for drugs (including cannabis), nicotine/cotinine, and/or alcohol use at Screening, subject has consumed alcohol within 24 hours prior to Visit 3 Subject has participated in any clinical study or had been treated with any investigational drugs within 28 days or 5 half-lives Female subject who is pregnant or breastfeeding. Subject has any episode of paradoxical bronchospasm in the past 12 months. Subject has pacemaker; is not in sinus rhythm; has a corrected QT interval (QTc; using Fridericia's [QTcF] formula) of >450 ms (for males) and >470 ms (for females); or has a left bundle branch block or bifascicular block. Subject has a pulse <40 or >100 bpm; systolic blood pressure >140 mmHg, or diastolic blood pressure >90 mmHg at Screening Subject has Type I or II diabetes requiring medication. Subject has received any vaccine within 30 days prior to Day 1. Subject has received any of the following immunosuppressant therapies within 6 months prior to Screening: imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, or methotrexate. Subject has received any antibody or therapeutic biologic product during the 6 months prior to Screening. Subject has received any oral, intravenous, or intramuscular steroid within 4 weeks prior to Screening. Intrathecal or intraarticular steroids are permitted. A subject who is not vaccinated with the COVID-19 vaccine with appropriate window from last dose of vaccine to Screening per local guidelines, policies, and availability within 30 days prior to Day 1. Part C: Any subject who meets any of these criteria must be excluded from Part C of this study: History of any illness or any clinical condition that might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. Any of the following abnormal laboratory tests: Hemoglobin, Total bilirubin, liver enzymes or creatine clearance An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for sinopulmonary disease within 28 days before the screening visit. An acute illness not related to CF within 14 days before the first dose of study drug. Subject has an active COVID-19 infection within 4 weeks prior to screening. Ongoing or prior participation in a study of an investigational treatment within 28 days or 5 terminal half-lives (whichever is longer) before screening. Female subject who is pregnant or breastfeeding. Please refer to study protocol for the complete inclusion/exclusion criteria list.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shirley W Lyons, MS
Phone
6504307235
Email
slyons@cysteticmedicines.com
First Name & Middle Initial & Last Name or Official Title & Degree
Daniele Tompkins, MA
Phone
973-983-3700
Ext
205
Email
dtompkins@devprobiopharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Burke, MD, PhD
Organizational Affiliation
Founder of cystetic Medicines
Official's Role
Study Chair
Facility Information:
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
New Zealand Clinical Research
City
Christchurch
Country
New Zealand
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Study to Assess Amphotericin B Cystetic for Inhalation (ABCI) Doses in Healthy Volunteers & People With Cystic Fibrosis

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