Cystic Fibrosis
Conditions
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.
Interventions
COMBINATION_PRODUCTABCI
Subjects will receive ABCI via oral inhalation
COMBINATION_PRODUCTPlacebo
Subjects will receive ABCI via oral inhalation
Sponsors
DevPro Biopharma
Cystetic Medicines, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs), and Serious Adverse Events (SAEs) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) Profile - SAD Tmax | 1 day | Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax) |
| Pharmacokinetics (PK) Profile - SAD AUC0-24 | 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 | 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 | 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 | 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 - SAD Cmax | 1 day | Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax) |
| Pharmacokinetics (PK) Profile - MAD Tmax | Up to 28 days | Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: time to reach maximum concentration (Tmax) |
| Pharmacokinetics (PK) Profile - MAD AUC0-24 | 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 | Up to 84 days | Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Plasma AmB assessments |
| Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid | 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 | Through 42 days | Cumulative effect on pre-dose AmB concentrations through Day 29 and assessment of washout through Day 42 |
| Pharmacokinetics (PK) Profile - MAD Cmax | Up to 28 days | Pharmacokinetics Characteristics in Multiple Ascending Dose HV Subjects: Observed maximum concentration (Cmax) |
Other
| Measure | Time frame | Description |
|---|---|---|
| ppFEV1 - Subjects with CF | 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 |
| IVIVC - FEV1 & ASL pH - Subjects with CF | 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 |
| LCI - Subjects with CF | Up to 42 days | Absolute change in Lung Clearance Index (LCI) (where available) |
| Questionnaire - Subjects with CF | 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 | 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 | 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 | 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 | 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 | 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 | Day 29 | Absolute change in % solids in sputum from baseline (optional) |
| FRI biomarkers - Subjects with CF | 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 | 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 | 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 | Up to 42 days | Change in ASL pH in response to AmB in vitro in primary cultured nasal epithelial cells |
Countries
Australia, New Zealand
Contacts
Primary ContactMartin Burke, MD, PhD
Backup ContactDaniele Tompkins, MA
Outcome results
None listed