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

Официальное название

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)

Обзор

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.

Вмешательства

• Комбинированный продукт ABCI
  Subjects will receive ABCI via oral inhalation
• Комбинированный продукт Placebo
  Subjects will receive ABCI via oral inhalation

Первичные конечные точки

• Adverse Events (AEs), and Serious Adverse Events (SAEs) [Срок оценки: up to 10 weeks]

Вторичные конечные точки (12)

• Pharmacokinetics (PK) Profile - SAD Cmax [Срок оценки: 1 day]
• Pharmacokinetics (PK) Profile - SAD Tmax [Срок оценки: 1 day]
• Pharmacokinetics (PK) Profile - SAD AUC0-24 [Срок оценки: 1 day]
• Pharmacokinetics (PK) Profile - SAD AUClast [Срок оценки: 1 day]
• Pharmacokinetics (PK) Profile - SAD AUCinf [Срок оценки: 1 day]
• Pharmacokinetics (PK) Profile - SAD AUCtau [Срок оценки: Up to 28 days]
• Pharmacokinetics (PK) Profile - MAD Cmax [Срок оценки: Up to 28 days]
• Pharmacokinetics (PK) Profile - MAD Tmax [Срок оценки: Up to 28 days]
• Pharmacokinetics (PK) Profile - MAD AUC0-24 [Срок оценки: Up to 28 days]
• Pharmacokinetics (PK) Profile - MAD Plasma AmB assessments [Срок оценки: Up to 84 days]
• Pharmacokinetics (PK) Profile - MAD AmB concentrations in BAL fluid [Срок оценки: Up to 29 days]
• AmB concentrations - Subjects with CF [Срок оценки: Through 42 days]

Критерии участия

Критерии включения

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

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 4 центра

• Canberra Hospital — Canberra
• Westmead Hospital — Westmead
• The Prince Charles Hospital — Brisbane
• Monash Medical Centre — Clayton

Новая Зеландия · 1 центр

• New Zealand Clinical Research — Christchurch

Идентификаторы

NCT: NCT05802264 · CM001001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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