Chronic Obstructive Pulmonary Disease, Non-cystic Fibrosis Bronchiectasis
Conditions
Brief summary
This study evaluates the safety, tolerability, and activity of inhaled GDC-6988 in participants with muco-obstructive disease.
Interventions
DRUGGDC-6988
GDC-6988 will be administered using a dry powder inhalation (DPI) device.
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 in Part B * Chronic sputum production of ≥1 teaspoon per day as reported in the sputum volume item * Ability to produce a sputum sample that is suitable for central laboratory determination of mucus percent solids and sialic acid concentration exploratory biomarker research, and biomarker assay development * Availability of a representative blood sample for exploratory biomarker research and biomarker assay development Additional Inclusion Criteria for Participants With Non-cystic Fibrosis Bronchiectasis (NCFB) (Cohort 1, Cohort 2, and Cohort 3): \- Diagnosis of bronchiectasis on the basis of prior chest computed tomography (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 Chronic Obstructive Pulmonary Disease (COPD) (Cohort 1, Cohort 2, and Cohort 4): * COPD defined as post-bronchodilator FEV1/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) or non-smoker with at least one documented COPD risk factor
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 milliliter (mL) within 3 months prior to screening * Known immunodeficiency that, in the investigator's judgment, is clinically significant and places the individual at a substantially elevated risk for opportunistic infections. * 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 electrocardiogram (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 milliseconds (ms) for males or \>470 ms for females Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs), with Severity Assessed by Division of Acquired Immunodeficiency Syndrome (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
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants With Spirometry Abnormalities Without and With Albuterol Pretreatment | 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 | Part A: Day 1 and Day 2, Part B: Day 1, Day 8 and Day 15 | Other relevant pharmacokinetic (PK) parameters may be assessed. |
| Part B: Change From Baseline in Sputum Percent Solids at Day 8 and Day 14 | Baseline, at Day 8 and at Day 14 | — |
| Part B: Change From Baseline in Whole-lung Mucociliary Clearance (MCC) Scintigraphy at Day 8 | Baseline and at Day 8 | — |
| Part B: Change From Baseline in Sputum Percent Solids at Day 15 | Baseline and at Day 15 | — |
| Part B: Change From Baseline in Whole-lung MCC Scintigraphy at Day 15 | Baseline and at Day 15 | — |
Countries
United States
Contacts
CONTACTReference Study ID Number: GB45429 https://forpatients.roche.com/
CONTACTFastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Genentech, Inc.
Outcome results
None listed