A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-obstructive Disease

NCT06603246 | Recruiting Phase 1 FDA Drug

• 1 other identifier: GB45429
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 7

Brief Summary

This study evaluates the safety, tolerability, and activity of inhaled GDC-6988 in participants with muco-obstructive disease.

Conditions

Non-cystic Fibrosis Bronchiectasis; Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Adverse Events (AEs), with Severity Assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grading Scale

  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).

  From baseline up to 6 weeks

• Percentage of Participants With Spirometry Abnormalities

  From baseline up to 6 weeks

Secondary Outcomes (6)

• Part A: Percentage of Participants With Spirometry Abnormalities Without and With Albuterol Pretreatment

  From baseline up to 6 weeks

• Plasma Concentration of GDC-6988 at Specified Timepoints

  Part A: Day 1 and Day 2, Part B: Day 1, Day 8 and Day 15

• 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

Study Arms (1)

GDC-6988

EXPERIMENTAL

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 low-dose, followed by high-dose GDC-6988, BID for 14 days. Participants in Cohorts 3 and 4 will receive low-dose GDC-6988, BID for 14 days.

Drug: GDC-6988

Interventions

GDC-6988 DRUG

GDC-6988 will be administered using a dry powder inhalation (DPI) device.

Also known as: RO7506811

GDC-6988

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• \- 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
• 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

You may not qualify if:

• 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
• 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
• Diagnosis of asthma, that in the investigator's judgment, is the primary driver of the individual's respiratory disease (e.g., primary asthma with incidental bronchiectasis findings)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (7)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Accel Research Site - Achieve - Birmingham - ERN - PPDS

Vestavia Hills, Alabama, 35216-1927, United States

WITHDRAWN

Stanford Center for Excellence in Pulmonary Biology

Palo Alto, California, 94304, United States

RECRUITING

University of Kansas Medical Center-Kansas City-3901 Rainbow Blvd

Kansas City, Kansas, 66160 8500, United States

RECRUITING

University of North Carolina Clinical Research Center

Chapel Hill, North Carolina, 27514, United States

RECRUITING

UPMC Montefiore Hospital

Pittsburgh, Pennsylvania, 15213 3236, United States

RECRUITING

TTS Research

Boerne, Texas, 78006, United States

COMPLETED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: GB45429 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 19, 2024
• Study Start: November 18, 2024
• Primary Completion (Estimated): November 15, 2027
• Study Completion (Estimated): November 15, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)