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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05802264




Registration number
NCT05802264
Ethics application status
Date submitted
28/02/2023
Date registered
6/04/2023
Date last updated
31/05/2024

Titles & IDs
Public title
Study to Assess Amphotericin B Cystetic for Inhalation (ABCI) Doses in Healthy Volunteers & People With Cystic Fibrosis
Scientific 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)
Secondary ID [1] 0 0
CM001001
Universal Trial Number (UTN)
Trial acronym
ABCI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination Product - ABCI
Combination Product - Placebo

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

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.

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.


Combination Product: ABCI
Subjects will receive ABCI via oral inhalation

Combination Product: Placebo
Subjects will receive ABCI via oral inhalation
Intervention code [1] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events (AEs), and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
up to 10 weeks
Secondary outcome [1] 0 0
Pharmacokinetics (PK) Profile - SAD Cmax
Timepoint [1] 0 0
1 day
Secondary outcome [2] 0 0
Pharmacokinetics (PK) Profile - SAD Tmax
Timepoint [2] 0 0
1 day
Secondary outcome [3] 0 0
Pharmacokinetics (PK) Profile - SAD AUC0-24
Timepoint [3] 0 0
1 day
Secondary outcome [4] 0 0
Pharmacokinetics (PK) Profile - SAD AUClast
Timepoint [4] 0 0
1 day
Secondary outcome [5] 0 0
Pharmacokinetics (PK) Profile - SAD AUCinf
Timepoint [5] 0 0
1 day
Secondary outcome [6] 0 0
Pharmacokinetics (PK) Profile - SAD AUCtau
Timepoint [6] 0 0
Up to 28 days
Secondary outcome [7] 0 0
Pharmacokinetics (PK) Profile - MAD Cmax
Timepoint [7] 0 0
Up to 28 days
Secondary outcome [8] 0 0
Pharmacokinetics (PK) Profile - MAD Tmax
Timepoint [8] 0 0
Up to 28 days
Secondary outcome [9] 0 0
Pharmacokinetics (PK) Profile - MAD AUC0-24
Timepoint [9] 0 0
Up to 28 days
Secondary outcome [10] 0 0
Pharmacokinetics (PK) Profile - MAD Plasma AmB assessments
Timepoint [10] 0 0
Up to 84 days
Secondary outcome [11] 0 0
Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid
Timepoint [11] 0 0
Up to 29 days
Secondary outcome [12] 0 0
AmB concentrations - Subjects with CF
Timepoint [12] 0 0
Through 42 days

Eligibility
Key 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
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
The Prince Charles Hospital - Brisbane
Recruitment hospital [4] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4032 - Brisbane
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cystetic Medicines, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
DevPro Biopharma
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05802264
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martin Burke, MD, PhD
Address 0 0
Founder of cystetic Medicines
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Shirley W Lyons, MS
Address 0 0
Country 0 0
Phone 0 0
6504307235
Fax 0 0
Email 0 0
slyons@cysteticmedicines.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05802264