- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05802264
Study to Assess Amphotericin B Cystetic for Inhalation (ABCI) Doses in Healthy Volunteers & People With Cystic Fibrosis (ABCI)
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Shirley W Lyons, MS
- Phone Number: 6504307235
- Email: slyons@cysteticmedicines.com
Study Contact Backup
- Name: Daniele Tompkins, MA
- Phone Number: 205 973-983-3700
- Email: dtompkins@devprobiopharma.com
Study Locations
-
-
Australian Capital Territory
-
Canberra, Australian Capital Territory, Australia, 2605
- Not yet recruiting
- Canberra Hospital
-
Contact:
- Yashneel Prasad, MD
-
Contact:
- Joelle Bourke
-
-
New South Wales
-
Westmead, New South Wales, Australia, 2145
- Not yet recruiting
- Westmead Hospital
-
Contact:
- Jimmy Chien, MD
-
Contact:
- Tracey Burns
-
-
Queensland
-
Brisbane, Queensland, Australia, 4032
- Recruiting
- The Prince Charles Hospital
-
Contact:
- Ieuan Evans, MD
-
Contact:
- Michelle Wood
-
-
Victoria
-
Clayton, Victoria, Australia, 3168
- Not yet recruiting
- Monash Medical Centre
-
Contact:
- Christopher Daley, MD
-
Contact:
- Corinne Van Asha
-
-
-
-
-
Christchurch, New Zealand
- Recruiting
- New Zealand Clinical Research
-
Contact:
- Cory Sellwood, MD
-
Contact:
- David Lee
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
- For subjects on CFTR modulators: FEV1 ≥40% and ≤90%
- For subjects not on CFTR modulators: FEV1 ≥40% and ≤100%
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part A Healthy Volunteer
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 receive ABCI via oral inhalation
Other Names:
Subjects will receive ABCI via oral inhalation
|
Experimental: Part B Healthy Volunteer
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 receive ABCI via oral inhalation
Other Names:
Subjects will receive ABCI via oral inhalation
|
Experimental: Part C People with Cystic Fibrosis
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 20 subjects with CF, including 2 sentinels subjects not on cystic fibrosis transmembrane conductance regulator (CFTR) modulators will be enrolled.
The 2 sentinel subjects will receive the medium dose/regimen.
If the medium dose/regimen is tolerated, the remaining subjects with CF will receive the high dose/regimen of ABCI and may be either on CFTR modulators or not on CFTR modulators.
|
Subjects will receive ABCI via oral inhalation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events (AEs), and Serious Adverse Events (SAEs)
Time Frame: up to 10 weeks
|
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
|
up to 10 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics (PK) Profile - SAD Cmax
Time Frame: 1 day
|
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
|
1 day
|
Pharmacokinetics (PK) Profile - SAD Tmax
Time Frame: 1 day
|
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
|
1 day
|
Pharmacokinetics (PK) Profile - SAD AUC0-24
Time Frame: 1 day
|
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
|
1 day
|
Pharmacokinetics (PK) Profile - SAD AUClast
Time Frame: 1 day
|
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)
|
1 day
|
Pharmacokinetics (PK) Profile - SAD AUCinf
Time Frame: 1 day
|
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf)
|
1 day
|
Pharmacokinetics (PK) Profile - MAD Cmax
Time Frame: Up to 28 days
|
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
|
Up to 28 days
|
Pharmacokinetics (PK) Profile - MAD Tmax
Time Frame: Up to 28 days
|
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
|
Up to 28 days
|
Pharmacokinetics (PK) Profile - MAD AUC0-24
Time Frame: Up to 28 days
|
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
|
Up to 28 days
|
Pharmacokinetics (PK) Profile - SAD AUCtau
Time Frame: Up to 28 days
|
Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Area under the concentration- concentration-time curve over the dosing interval (AUCtau)
|
Up to 28 days
|
Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid
Time Frame: Up to 29 days
|
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: AmB concentrations in BAL fluid after study drug administration
|
Up to 29 days
|
AmB concentrations - Subjects with CF
Time Frame: Through 42 days
|
Cumulative effect on pre-dose AmB concentrations through Day 29 and assessment of washout through Day 42
|
Through 42 days
|
Pharmacokinetics (PK) Profile - MAD Plasma AmB assessments
Time Frame: Up to 84 days
|
Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB assessments
|
Up to 84 days
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ppFEV1 - Subjects with CF
Time Frame: Up to 42 days
|
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
|
Up to 42 days
|
LCI - Subjects with CF
Time Frame: Up to 42 days
|
Absolute change in Lung Clearance Index (LCI) (where available)
|
Up to 42 days
|
ppFVC - Subjects with CF
Time Frame: Up to 42 days
|
Absolute change in percent-predicted morning pre-dose forced vital capacity (ppFVC) from baseline to Day 29 and from Day 29 to Day 42
|
Up to 42 days
|
FVC - Subjects with CF
Time Frame: Up to 42 days
|
Absolute change in morning pre-dose FVC from baseline to Day 29 and from Day 29 to Day 42 (mLs)
|
Up to 42 days
|
FEV1 - Subjects with CF
Time Frame: Up to 42 days
|
Absolute change in morning pre-dose FEV1 from baseline to Day 29 and from Day 29 to Day 42 (mLs)
|
Up to 42 days
|
DLCO - Subjects with CF
Time Frame: Up to 29 days
|
Absolute change in diffusing capacity of the lungs for carbon monoxide (DLCO [expressed as percent-predicted corrected for hemoglobin]) from baseline to Day 29
|
Up to 29 days
|
Body weight - Subjects with CF
Time Frame: Up to 42 days
|
Absolute change in body weight from baseline to Day 29 and from Day 29 to Day 42
|
Up to 42 days
|
FRI biomarkers - Subjects with CF
Time Frame: Up to 28 days
|
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)
|
Up to 28 days
|
IVIVC - chloride secretion - Subjects with CF
Time Frame: Up to 42 days
|
Change in chloride secretion in response to AmB in vitro in primary cultured nasal epithelial cells
|
Up to 42 days
|
IVIVC - FEV1 - Subjects with CF
Time Frame: Up to 42 days
|
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
|
Up to 42 days
|
IVIVC - ASL pH - Subjects with CF
Time Frame: Up to 42 days
|
Change in ASL pH in response to AmB in vitro in primary cultured nasal epithelial cells
|
Up to 42 days
|
IVIVC - FEV1 & ASL pH - Subjects with CF
Time Frame: Up to 29 days
|
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
|
Up to 29 days
|
Questionnaire - Subjects with CF
Time Frame: Up to 42 days
|
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.
|
Up to 42 days
|
% solids in sputum - Subjects with CF
Time Frame: Day 29
|
Absolute change in % solids in sputum from baseline (optional)
|
Day 29
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Martin Burke, MD, PhD, Founder of cystetic Medicines
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Infant, Newborn, Diseases
- Genetic Diseases, Inborn
- Pancreatic Diseases
- Fibrosis
- Cystic Fibrosis
- Anti-Infective Agents
- Anti-Bacterial Agents
- Antifungal Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Amebicides
- Amphotericin B
Other Study ID Numbers
- CM001001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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