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

• ClinicalTrials.gov Identifier: NCT05802264
• Recruitment Status: Recruiting
• First Posted: April 6, 2023
• Last Update Posted: March 13, 2024
• Sponsor: Cystetic Medicines, Inc.
• Collaborator: DevPro Biopharma
• Information provided by (Responsible Party): Cystetic Medicines, Inc.

Tracking Information

• First Submitted Date: February 28, 2023
• First Posted Date: April 6, 2023
• Last Update Posted Date: March 13, 2024
• Actual Study Start Date: March 21, 2023
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 4, 2023)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 11, 2024)

• Pharmacokinetics (PK) Profile - SAD Cmax [ Time Frame: 1 day ]
  Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
• Pharmacokinetics (PK) Profile - SAD Tmax [ Time Frame: 1 day ]
  Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
• 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)
• 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)
• 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)
• 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)
• Pharmacokinetics (PK) Profile - MAD Cmax [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
• 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)
• 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)
• Pharmacokinetics (PK) Profile - MAD Plasma AmB assessments [ Time Frame: Up to 84 days ]
  Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB assessments
• 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
• 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

Original Secondary Outcome Measures (submitted: April 4, 2023)

• Pharmacokinetics (PK) Profile - SAD Cmax [ Time Frame: 1 day ]
  Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
• Pharmacokinetics (PK) Profile - SAD Tmax [ Time Frame: 1 day ]
  Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
• 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)
• 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)
• 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)
• Pharmacokinetics (PK) Profile - MAD Cmax [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
• 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)
• 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)
• 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)
• Pharmacokinetics (PK) Profile - MAD Plasma AmB trough assessments [ Time Frame: Up to 84 days ]
  Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB trough assessments
• Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: AmB concentrations in BAL fluid after study drug administration
• Pharmacokinetics (PK) Profile - Subjects with CF Cmax [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Subjects with Cystic Fibrosis: Observed maximum concentration (Cmax)
• Pharmacokinetics (PK) Profile - Subjects with CF Tmax [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Subjects with Cystic Fibrosis: time to reach maximum concentration (Tmax)
• Pharmacokinetics (PK) Profile - Subjects with CF AUC0-24 [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Subjects with Cystic Fibrosis: Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
• Pharmacokinetics (PK) Profile - Subjects with CF AUCtau [ Time Frame: Up to 28 days ]
  Pharmacokinetics Characteristics in Subjects with Cystic Fibrosis: Area under the concentration- concentration-time curve over the dosing interval (AUCtau)
• Pharmacokinetics (PK) Profile - Subjects with CF trough AmB concentrations [ Time Frame: Up to 42 days ]
  Pharmacokinetics Characteristics in Subjects with Cystic Fibrosis: Cumulative effect on trough AmB concentrations
• Pharmacokinetics (PK) Profile - Subjects with CF Plasma AmB trough assessments [ Time Frame: Up to 84 days ]
  Pharmacokinetics Characteristics in Subjects with Cystic Fibrosis: Plasma AmB trough assessments
• FEV1 - Subjects with CF [ Time Frame: Up to 42 days ]
  Characteristics in Subjects with Cystic Fibrosis: Absolute change in morning pre-dose and percent-predicted morning pre-dose forced expiratory volume in 1 second (FEV1) from baseline to Day 29 and to Day 42
• Questionnaire - Subjects with CF [ Time Frame: Up to 42 days ]
  Absolute change in CF Questionnaire in Subjects with Cystic Fibrosis: Revised (CFQ-R) respiratory domain score from baseline to Day 29 and to Day 42
• FVC - Subjects with CF [ Time Frame: Up to 42 days ]
  Characteristics in Subjects with Cystic Fibrosis: Absolute change in percent-predicted morning pre-dose forced vital capacity (FVC) from baseline to Day 29 and to Day 42
• Body weight - Subjects with CF [ Time Frame: Up to 42 days ]
  Characteristics in Subjects with Cystic Fibrosis: Absolute change in body weight from baseline to Day 29 and to Day 42

Current Other Pre-specified Outcome Measures (submitted: March 11, 2024)

• 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
• LCI - Subjects with CF [ Time Frame: Up to 42 days ]
  Absolute change in Lung Clearance Index (LCI) (where available)
• 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.
• 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
• 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)
• 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)
• 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
• 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
• % solids in sputum - Subjects with CF [ Time Frame: Day 29 ]
  Absolute change in % solids in sputum from baseline (optional)
• 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)
• 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
• 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
• 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
• 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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess Amphotericin B Cystetic for Inhalation (ABCI) Doses in Healthy Volunteers & People With Cystic Fibrosis
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Combination Product: ABCI
  Subjects will receive ABCI via oral inhalation
  Other Name: Amphotericin B Cystetic for Inhalation
• Combination Product: Placebo
  Subjects will receive ABCI via oral inhalation

Study Arms

• 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
  Interventions:

  • Combination Product: ABCI
  • Combination Product: 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.
  Interventions:

  • Combination Product: ABCI
  • Combination Product: 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.
  Intervention: Combination Product: ABCI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 17, 2023): 84
• Original Estimated Enrollment (submitted: April 4, 2023): 96
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

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.

Please refer to study protocol for the complete inclusion/exclusion criteria list.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Shirley W Lyons, MS; 6504307235; slyons@cysteticmedicines.com

Contact: Daniele Tompkins, MA; 973-983-3700 ext 205; dtompkins@devprobiopharma.com

• Listed Location Countries: Australia, New Zealand

Administrative Information

• NCT Number: NCT05802264
• Other Study ID Numbers: CM001001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cystetic Medicines, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Cystetic Medicines, Inc.
• Original Study Sponsor: Same as current
• Collaborators: DevPro Biopharma

Investigators

• Study Chair: Martin Burke, MD, PhD; Founder of cystetic Medicines

• PRS Account: Cystetic Medicines, Inc.
• Verification Date: March 2024