A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease
Phase 1
Recruiting
- Conditions
- Non Cystic Fibrosis BronchiectasisChronic Obstructive Pulmonary Disease
- Interventions
- Registration Number
- NCT06603246
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This study evaluates the safety, tolerability, and activity of inhaled GDC-6988 in patients with muco-obstructive disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 128
Inclusion Criteria
- Percent predicted FEV1 ≥ 40% by spirometry during screening
- Ability to demonstrate correct use of the Smart DPI at screening, in the investigator's judgment
- On a stable treatment regimen for muco-obstructive diseases for ≥ 28 days prior to initiation of study treatment and willingness to remain on the stable treatment regimen through completion of study
- Stable disease for ≥ 28 days prior to screening and through to initiation of study treatment
Additional Inclusion Criteria for Participants with NCFB (Cohort 1, Cohort 2, and Cohort 3):
- Diagnosis of bronchiectasis on the basis of prior chest CT, involving at least 2 lobes, with at least one lobe of involvement in the right lung as assessed by the investigator
Additional Inclusion Criteria for Participants with COPD (Cohort 1 and Cohort 4):
- COPD defined as post-bronchodilator FEV1/forced vital capacity (FVC) ratio of <0.7
- Chronic bronchitis, with a definition including chronic cough and excessive sputum production for more than 3 months per year for at least 2 years prior to screening
- Former smoker with a minimum of 10 pack-year history (e.g., 20 cigarettes/day for 10 years)
Exclusion Criteria
- Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the timeframe in which contraception is required
- Known significant bronchodilator response of >10% predicted change in FEV1 or FVC, in the investigator's judgment
- Use of any prohibited medications
- Acute respiratory infection within 28 days of screening
- Significant hemoptysis greater than 60 mL within 3 months prior to screening
- Known immunodeficiency including, but not limited to, HIV infection with CD4+ T cell count <200 cells/mm3 or an AIDS-defining condition 6 months prior to screening
- Known substance abuse, in the investigator's judgment, within 12 months prior to screening
- Poor peripheral venous access
- Receipt of blood products within 120 days prior to screening
- Any medical condition or abnormal clinical laboratory finding that, in the investigator's judgment, would preclude the individual's safe participation in and completion of the study or could affect the interpretation of the results
- History of thoracic or metastatic malignancy within 5 years prior to screening
- Known history of a clinically significant abnormal ECG, or presence of an abnormal ECG that is deemed clinically significant by the investigator
- QT interval corrected through use of Fridericia's formula (QTcF) >450 ms for males or >470 ms for females
Additional Exclusion Criteria for Participants with NCFB (Cohort 1, Cohort 2, and Cohort 3)
- Bronchiectasis primarily due to cystic fibrosis, primary ciliary dyskinesia, non-tuberculous mycobacterial infection, chronic aspiration, or predominantly traction bronchiectasis due to interstitial lung disease (ILD), in the investigator's judgment
- Primary diagnosis of COPD or asthma, in the investigator's judgment
- NCFB exacerbation within 28 days prior to screening or that has not returned to baseline
- Current smoker: Current smoking is defined as any use of inhaled tobacco products or inhaled marijuana within 3 months prior to screening, through use of cigarettes, cigars, electronic cigarettes, vaporizing devices, or pipes.
Additional Exclusion Criteria for Participants with COPD (Cohort 1 and Cohort 4):
- COPD exacerbation within 28 days prior to screening or that has not returned to baseline
- Asthma/COPD overlap syndrome
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GDC-6988 GDC-6988 Participants in cohort 1 will receive low dose GDC-6988 twice a day (BID) on Day 1 followed by high dose BID on Day 2. Participants in cohort 2 will receive high dose GDC-6988 BID for 14 days. Participants in Cohorts 3 and 4 will receive low dose GDC-6988 BID for 14-days.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse events (AEs), with Severity assessed by Division of AIDS (DAIDS) Toxicity Grading Scale From Baseline up to 6 Weeks The AEs will be graded according to the DAIDS table for grading the severity. The severity level is graded from grade 1 (mild) to 4 (Potentially Life-Threatening)
Percentage of Participants with Spirometry Abnormalities From Baseline up to 6 Weeks
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Spirometry Abnormalities Without and With Albuterol Pretreatment Part A and Part B - From Baseline up to 6 Weeks Spirometric abnormalities related to forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal (peak) inspiratory flow rate, and flow-volume loops will be reported.
Plasma concentration of GDC-6988 at Specified Timepoints and Relevant Pharmacokinetic (PK) Parameters Part A- Day 1 and Day 2, Part-B Day 1, Day 8 and Day 15 Change from Baseline in Sputum Percent Solids at Day 8 and Day 14 Part B- Baseline, at Day 8 and at Day 14 Change from Baseline in Whole-Lung mucociliary clearance (MCC) Scintigraphy at Day 8 Part B- Baseline and at Day 8 Change from Baseline in Sputum Percent Solids at Day 15 Part B- Baseline and at Day 15 Change from Baseline in Whole-Lung MCC Scintigraphy at Day 15 Part B- Baseline and at Day 15
Trial Locations
- Locations (2)
Accel Research Site - Achieve - Birmingham - ERN - PPDS
🇺🇸Vestavia Hills, Alabama, United States
TTS Research
🇺🇸Boerne, Texas, United States