None listed
Conditions
Brief summary
The purpose of this study is to test the safety of GDC-4379 at different dose levels and to find out what effects, good or bad, GDC-4379 has on volunteers. This study will be conducted in three parts. Part A and Part B will be in healthy volunteers between the ages of 18 and 65 years and Part C in patients with mild asthma between the ages of 18 and 65 years.
Interventions
For Part A, healthy volunteers will receive a single inhaled dose of GDC-4379 or placebo. The starting dose will be 1 mg inhaled. A total of 6 dose cohorts are planned: Cohort A, B, C, D, H and I. The dose will be increased by approximately 2- to 3-fold (i.e., half-log or less) increments for each successive cohort. Actual doses may be adjusted depending on the outcome of preceding cohorts. Doses will be escalated based on safety, tolerability, and available PK data.
For Part B, healthy volun
For Part A, healthy volunteers will receive a single inhaled dose of GDC-4379 or placebo. The starting dose will be 1 mg inhaled. A total of 6 dose cohorts are planned: Cohort A, B, C, D, H and I. The dose will be increased by approximately 2- to 3-fold (i.e., half-log or less) increments for each successive cohort. Actual doses may be adjusted depending on the outcome of preceding cohorts. Doses will be escalated based on safety, tolerability, and available PK data. For Part B, healthy volunteers will receive an inhaled dose of GDC-4379 or placebo once or twice daily for a total of 14 days. A total of 4 dose cohorts are planned: Cohort E, F, Q and L. The dose will be increased by approximately 2- to 3-fold (i.e., half-log or less) increments for each successive cohort. Actual doses may be adjusted depending on the outcome of preceding cohorts. Doses will be escalated based on safety, tolerability, and available PK data. Daily dose will not exceed those evaluated in Part A. For Part C, patients with mild asthma will receive an inhaled dose of GDC-4379 or placebo once or twice daily for 14 days. A total of 3 dose cohorts are planned: Cohort M, S, and either P or T. The final dose cohort (P or T) will be determined after the completion of Part B Cohort L. Doses will be escalated based on safety, tolerability, and available PK/PD data. Dose and duration will not exceed those evaluated in Part B. For parts A, B and C all dosing will be done in clinic under the supervision of qualified medical staff. A Safety Monitoring committee that will include at minimum the Medical Monitor, a drug safety scientist, and a biostatistician from the Sponsor; and will be responsible for dose-escalation decisions, with consent from the investigator. NOTE: There have been several protocol amendments and study design iterations throughout the study, which resulted in cohorts G, J, K, N, O, R (each with varying doses) being eliminated from the study. These cohorts were never enrolled. To avoid potential confusion, any newly added cohorts were assigned the next available letter in the alphabet, rather than re-assigning a previously used letter from an eliminated cohort.
Sponsors
Genentech
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria for Healthy Volunteers • Signed Informed Consent Form • Age 18-65 years • Body mass index of 18-37 kg/m2 • Weight of 50-120 kg • In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs. • First forced expiratory volume (FEV1) >70 % predicted • Forced vital capacity (FVC) >2.0 L • Ability to demonstrate sufficient inspiratory effort using the inhaler training • Ability to comply with the study protocol, including all study procedures • Agreement to remain abstinent or use contraceptive methods • FeNO >25 ppb at screening for one specific cohort Key Inclusion Criteria for Patients with Mild Asthma • Signed Informed Consent Form • Age 18-65 years • Body mass index of 18-37 kg/m2 • Weight of 50-120 kg • Documented physician-diagnosed mild asthma for at least 6 months prior to screening, defined as: Asthma that is controlled with as-needed reliever medication with or without a leukotriene receptor antagonist • No use of inhaled corticosteroids within 60 days prior to initiation of study drug • FeNO >40 ppb at screening and at pre-randomization visit • No clinically significant ECG abnormalities • Clinical laboratory evaluations should be within the reference range for the test laboratory unless deemed not clinically significant by the investigator and Sponsor. • FEV1 >70 % predicted • FVC >2.0 L • Ability to demonstrate sufficient inspiratory effort using the inhaler training device • Ability to comply with the study protocol, including all study procedures • Agreement to remain abstinent or use contraceptive methods
Exclusion criteria
Key Exclusion Criteria for Healthy Volunteers Subjects who meet any of the following criteria will be excluded from Parts A and B: • History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, gastrointestinal, urologic, neurologic, or psychiatric disorders, in the investigator’s judgment •History of malignancy, except completely excised basal cell carcinoma or squamous cell carcinoma of the skin • History of nasal polyposis or nasal polyps identified during screening physical examination • History of anaphylaxis, hypersensitivity, or significant drug allergies • History of severe hypersensitivity to milk proteins • History or presence of an abnormal ECG that is clinically significant • Any medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the subject’s safe participation in and completion of the study • Illicit drug or alcohol abuse within 12 months prior to initiation of study drug • Positive alcohol screen at screening or pre-randomization • Recent history of smoking within the 30 days prior to initiation of study drug • Smokers not able to pass the tobacco-related screening and who cannot refrain from smoking during the study • Positive urine test for selected drugs of abuse at screening • Pregnant or breastfeeding, or intending to become pregnant during the study • Women of childbearing potential must have a negative pregnancy test result at screening or pre-randomization. • Use of any prescription medications and products within 7 days prior to initiation of study drug and throughout the study • Use of a investigational drug or recent participation in an investigational study • Positive for hepatitis panel at screening Exclusion Criteria for Patients with Mild Asthma Subjects who meet any of the following criteria will be excluded from Part C: • Any of the exclusion criteria for healthy volunteers above • Use of ICS therapy within 60 days prior to initiation of study drug • Lack of asthma control defined as respiratory symptoms requiring use of a reliever inhaler (e.g., 2 puffs of SABA) more than twice a day on a regular basis within 4 weeks prior to initiation of study drug (not including reliever medication used to prevent symptoms) • Recent asthma exacerbation requiring oral corticosteroid use or urgent medical care for asthma within 12 weeks prior to initiation of study drug • Any asthma-related history, symptoms, or findings that precludes the subject’s safe participation in and completion of the study in the investigator’s judgment • Positive nasopharyngeal PCR test for SARS-COV-2 within 10 days prior to initiation of study drug
Outcome results
None listed