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

NCT ID: NCT05802264

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-21
• Study Completion Date: 2025-12-31

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 36 subjects with CF will receive the low dose, medium dose (2 sentinel subjects), or high dose of ABCI in Part C.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

ABCI

Intervention Type: COMBINATION_PRODUCT

Subjects will receive ABCI via oral inhalation

Placebo

Intervention Type: COMBINATION_PRODUCT

Subjects will receive ABCI via oral inhalation

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.

Group Type: EXPERIMENTAL

ABCI

Intervention Type: COMBINATION_PRODUCT

Subjects will receive ABCI via oral inhalation

Placebo

Intervention Type: COMBINATION_PRODUCT

Subjects will receive ABCI via oral inhalation

Part C People with Cystic Fibrosis

Subjects will be assigned to one of two planned dose cohorts of ABCI (loading dose 1.5 mg/0.5 mg daily, 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 36subjects 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 may receive the low, medium, high dose/regimen of ABCI and may be either on CFTR modulators or not on CFTR modulators. It is anticipated that approximately 24 subjects will be enrolled as follows: 8 high, 8 medium, and 8 low dose/regimen.

Group Type: EXPERIMENTAL

ABCI

Intervention Type: COMBINATION_PRODUCT

Subjects will receive ABCI via oral inhalation

Interventions

ABCI

Subjects will receive ABCI via oral inhalation

Intervention Type: COMBINATION_PRODUCT

Placebo

Subjects will receive ABCI via oral inhalation

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Amphotericin B Cystetic for Inhalation

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:
• 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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

DevPro Biopharma

INDUSTRY

Sponsor Role: collaborator

Cystetic Medicines, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Burke, MD, PhD

Role: STUDY_CHAIR

Founder of cystetic Medicines

Locations

Canberra Hospital

Canberra, Australian Capital Territory, Australia

Site Status: RECRUITING

Westmead Hospital

Westmead, New South Wales, Australia

Site Status: RECRUITING

The Prince Charles Hospital

Brisbane, Queensland, Australia

Site Status: RECRUITING

Monash Medical Centre

Clayton, Victoria, Australia

Site Status: RECRUITING

New Zealand Clinical Research

Christchurch, , New Zealand

Site Status: RECRUITING

Countries

Australia; New Zealand

Central Contacts

Martin Burke, MD, PhD

Role: CONTACT

mburke@cysteticmedicines.com

217-244-8726

Daniele Tompkins, MA

Role: CONTACT

dtompkins@devprobiopharma.com

973-983-3700 ext. 205

Facility Contacts

Yashneel Prasad, MD

Role: primary

Joelle Bourke

Role: backup

Jimmy Chien, MD

Role: primary

Tracey Burns

Role: backup

Ieuan Evans, MD

Role: primary

Michelle Wood

Role: backup

Christopher Daley, MD

Role: primary

Corinne Van Asha

Role: backup

Cory Sellwood, MD

Role: primary

David Lee

Role: backup

Other Identifiers

CM001001

Identifier Type: -

Identifier Source: org_study_id