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

Cystic Fibrosis Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05802264
• Other study ID #: CM001001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 21, 2023
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Cystetic Medicines, Inc.
• Contact: Shirley W Lyons, MS
• Phone: 6504307235
• Email: slyons[@]cysteticmedicines.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 approximately 20 subjects with CF will receive the medium dose (2 sentinel subjects) or high dose (up to 18 subjects) of ABCI in Part C.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Combination Product:
• ABCI
Subjects will receive ABCI via oral inhalation
• Placebo
Subjects will receive ABCI via oral inhalation

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
New Zealand	New Zealand Clinical Research	Christchurch

Sponsors (2)

Lead Sponsor	Collaborator
Cystetic Medicines, Inc.	DevPro Biopharma

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ppFEV1 - Subjects with CF	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
Other	LCI - Subjects with CF	Absolute change in Lung Clearance Index (LCI) (where available)	Up to 42 days
Other	Questionnaire - Subjects with CF	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
Other	ppFVC - Subjects with CF	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
Other	FVC - Subjects with CF	Absolute change in morning pre-dose FVC from baseline to Day 29 and from Day 29 to Day 42 (mLs)	Up to 42 days
Other	FEV1 - Subjects with CF	Absolute change in morning pre-dose FEV1 from baseline to Day 29 and from Day 29 to Day 42 (mLs)	Up to 42 days
Other	DLCO - Subjects with CF	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
Other	Body weight - Subjects with CF	Absolute change in body weight from baseline to Day 29 and from Day 29 to Day 42	Up to 42 days
Other	% solids in sputum - Subjects with CF	Absolute change in % solids in sputum from baseline (optional)	Day 29
Other	FRI biomarkers - Subjects with CF	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
Other	IVIVC - chloride secretion - Subjects with CF	Change in chloride secretion in response to AmB in vitro in primary cultured nasal epithelial cells	Up to 42 days
Other	IVIVC - FEV1 - Subjects with CF	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
Other	IVIVC - ASL pH - Subjects with CF	Change in ASL pH in response to AmB in vitro in primary cultured nasal epithelial cells	Up to 42 days
Other	IVIVC - FEV1 & ASL pH - Subjects with CF	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
Primary	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	up to 10 weeks
Secondary	Pharmacokinetics (PK) Profile - SAD Cmax	Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)	1 day
Secondary	Pharmacokinetics (PK) Profile - SAD Tmax	Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)	1 day
Secondary	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)	1 day
Secondary	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)	1 day
Secondary	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)	1 day
Secondary	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)	Up to 28 days
Secondary	Pharmacokinetics (PK) Profile - MAD Cmax	Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax)	Up to 28 days
Secondary	Pharmacokinetics (PK) Profile - MAD Tmax	Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)	Up to 28 days
Secondary	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)	Up to 28 days
Secondary	Pharmacokinetics (PK) Profile - MAD Plasma AmB assessments	Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB assessments	Up to 84 days
Secondary	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	Up to 29 days
Secondary	AmB concentrations - Subjects with CF	Cumulative effect on pre-dose AmB concentrations through Day 29 and assessment of washout through Day 42	Through 42 days