Phase 1 study for people with Cystic Fibrosis

Reproduced exactly, unedited. Written for researchers rather than for patients.

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.