Phase I trial to evaluate the safety and tolerability of GDC-4379 in healthy volunteers and patients with mild asthma
- Conditions
- AsthmaRespiratory - Asthma
- Registration Number
- ACTRN12619000227190
- Lead Sponsor
- Genentech
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 128
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective of this study is to characterize the safety profile associated with GDC-4379. This will be measured through the incidence and the severity of any adverse events, and change from baseline in vital signs, physical exam, laboratory test results, ECG, or spirometry. As a first-in-human study, the risks at this time are unknown. All adverse events (patient or investigator reported) will be classified using MedDRA coding system and the WHO Toxicity Grading Scale.[Adverse events will be reported after any occurrence after the first dose. Vital signs will be collected at each study visit for part A (visit days 1 through 15). For part B and C they will be collected on visit days (1-17, 21, 28, 35 and 42).]
- Secondary Outcome Measures
Name Time Method To characterize the PK profile of GDC-4379, Plasma concentrations of GDC-4379 will be assessed and pharmacokinetic parameters such as through AUC, tmax, Cmax, and half-life will be calculated.[To characterize the PK profile of GDC 4379 16 plasma samples will be assessed for GDC-0214 concentrations during the course of the SAD in order to sufficiently characterize PK parameters such as Tmax, Cmax,t1/2, and AUC. Individual PK parameters will not be assessed at specific time points since they require the totality of the data. PK will be collected on Day 1 (pre-dose, (5 min, 15 min and 30 min post-dose and 1, 2, 4, 8, and 12 hours post-dose) ). On Day 2 (24h and 36h post-dose). On Day 3 (48hr post-dose). On Day 4 (72h post-dose) and anytime during visit days 6, 10 and 15.]