A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough
Phase 2
Completed
- Conditions
- Chronic Refractory Cough (CRC) With Non-atopic AsthmaCRC With Atopic AsthmaUnexplained Chronic CoughCRC With Chronic Obstructive Pulmonary DiseaseCRC With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis
- Interventions
- Registration Number
- NCT05660850
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This Phase IIa, multicenter, randomized, double-blind, placebo-controlled, crossover study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamic (PD) effects of GDC-6599 compared with placebo in patients with a history of chronic cough.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
Inclusion Criteria
- Previous diagnosis of CRC, despite optimized treatment for asthma or COPD, or UCC for at least 1 year
- Chest X-ray or computed tomography (CT) scan thorax within 5 years prior to screening visit that confirms the absence of any clinically significant abnormality contributing to the chronic cough in the opinion of the investigator
- Cough severity VAS score ≥ 40 at screening visit
- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 60% of predicted at screening"
- Mannitol CDR ≥ 12 coughs/100 mg determined at screening visit mannitol challenge test
- For women of childbearing potential: agreement to remain abstinent or use contraception For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm
Inclusion Criteria for Patients with CRC with Atopic Asthma or Patients with CRC with Non-Atopic Asthma (Part A)
- Physician diagnosis of asthma for ≥ 12 months based upon GINA STEP 2-5
- Stable treatment with ICS therapy (GINA STEP 2) or ICS therapy and at least one additional controller (GINA STEP 3- 5) for ≥ 3 months
- Patients with atopic asthma (n = 20), based upon historic record of positive test for atopy (if available), or confirmed at screening by positive fluorescence enzyme immunoassay for specific IgE against at least one of the following five perennial aeroallergens: animal (cat dander, dog dander, cockroach), dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), and mold mix
- Patients with non-atopic asthma (n = 20), based upon historic record of negative test for atopy (if available), or confirmed at screening by negative ImmunoCAP test result for all five perennial aeroallergens: animal (cat dander, dog dander, cockroach), dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), and mold mix, and relevant local allergens, and no history of symptoms suggesting atopy
- Never or former smoker (≥ 6 months prior to screening) with < 20 pack-years or equivalent history
Inclusion Criteria for Patients with CRC COPD-CB or Patients with CRC COPD (Part B)
- Diagnosis of COPD GOLD I-II ± CB
- Stable background treatment consisting of a bronchodilator medication and or stable ICS therapy for ≥ 12 weeks prior to screening visit
- Former smoker with ≥ 10 pack-years or equivalent history within 6 months of screening
- Post-bronchodilator FEV1/ forced vital capacity (FVC) ratio ≤ 0.70 at screening
- Chest X-ray or CT scan within 6 months prior to screening visit or during the screening period (prior to randomization [Study Visit 2]), that confirms the absence of clinically significant lung disease besides COPD
Exclusion Criteria
- Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 28 days after the final dose of GDC-6599
- History of diagnosed bleeding diathesis or easy bruising or bleeding
- Post-bronchodilator FEV1/ FVC ratio < 0.60 at screening visit (patients with CRC asthma and UCC only: Part A)
- History of significant hepatic impairment
- History of aspiration or recurrent pneumonia
- Respiratory infection (including upper respiratory infection) within 8 weeks prior to screening
- Treatment with any strong inhibitor or inducer of CYP3A within 28 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug
- Treatment with angiotensin-converting enzyme (ACE) inhibitor within 12 weeks prior to screening (Study Visit 1) through completion of the study
- Treatment with opioids (including codeine), pregabalin, gabapentin, amitriptyline, or nortriptyline for the treatment of cough within 2 weeks prior to screening (Study Visit 1) through completion of the study
- Treatment with cough suppressant medication within 2 weeks prior to screening (Study Visit 1) through completion of the study
- Known coronavirus 2019 (COVID-19) infection, persistent symptoms of known prior COVID-19 infection, and/or known positive COVID-19 test within at least 8 weeks prior to screening and randomization
- Clinical laboratory value outside the reference range for the test laboratory at screening
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
- History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A: CRC Asthma atopic GDC-6599 Patients with CRC atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: CRC Asthma atopic GDC-6599-matching placebo Patients with CRC atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: CRC Asthma atopic Mannitol Patients with CRC atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: CRC Asthma non-atopic GDC-6599-matching placebo Patients with CRC non-atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: CRC Asthma non-atopic Mannitol Patients with CRC non-atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: Unexplained Chronic Cough GDC-6599-matching placebo Patients with Unexplained Chronic Cough will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: Unexplained Chronic Cough Mannitol Patients with Unexplained Chronic Cough will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease GDC-6599 Patients with Chronic Obstructive Pulmonary Disease will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5. Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease GDC-6599-matching placebo Patients with Chronic Obstructive Pulmonary Disease will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5. Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease Mannitol Patients with Chronic Obstructive Pulmonary Disease will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5. Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis GDC-6599-matching placebo Patients with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5. Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis Mannitol Patients with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5. Part A: CRC Asthma non-atopic GDC-6599 Patients with CRC non-atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part A: Unexplained Chronic Cough GDC-6599 Patients with Unexplained Chronic Cough will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5 Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis GDC-6599 Patients with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5.
- Primary Outcome Measures
Name Time Method Change in cough frequency per hour, assessed objectively over 24 hours (24-hour OCC) using VitaloJAK cough recorder From baseline to Day 14 OCC - objective cough count over 24 hours
- Secondary Outcome Measures
Name Time Method Change in the severity of cough, as assessed through the use of the patient-reported cough severity VAS score From baseline to Day 14 VAS - visual analog scale
Change in the severity of cough, as assessed through the use of the patient-reported cough severity NRS score From baseline to Day 14 NRS - numeric response scale
Change in cough hypersensitivity to mannitol, measured as the CDR to mannitol From baseline to Day 14 CDR - coughs-per-dose ratio
Change in mannitol-induced AHR From baseline to Day 14 AHR - airway hyperresponsiveness calculated as maximum percent decrease in FEV1 after the last dose of mannitol divided by cumulative dose of mannitol administered during mannitol challenge test
Incidence and severity of adverse events, with severity determined according to the DAIDS toxicity grading scale From baseline to Day 14
Trial Locations
- Locations (20)
Box Hill Hospital; Eastern Clinical Research Unit
🇦🇺Box Hill, Victoria, Australia
Southern California Institute For Respiratory
🇺🇸Los Angeles, California, United States
Queen Anne Street Medical Centre
🇬🇧London, United Kingdom
California Medical Research Associates, Inc.
🇺🇸Northridge, California, United States
ADAC Research PA
🇺🇸Greenville, South Carolina, United States
Pharmaceutical Research & Consulting, Inc.
🇺🇸Dallas, Texas, United States
Mater Hospital Brisbane
🇦🇺South Brisbane, Queensland, Australia
TrialsWest Pty Ltd
🇦🇺Spearwood, Western Australia, Australia
Pioneer Clinical Studies
🇺🇸Miami, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Clinical Research Associates Of Central Pa , Llc
🇺🇸DuBois, Pennsylvania, United States
Bellingham Asthma, Allergy & Immunology
🇺🇸Bellingham, Washington, United States
McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
Diex Recherche - Québec - HyperCore - PPDS
🇨🇦Quebec, Canada
Royal Infirmary of Edinburgh
🇬🇧Edinburgh, United Kingdom
Hull York Medical School Centre for Cardiovascular and Metabolic Research
🇬🇧Kingston-upon-Hull, United Kingdom
Glenfield Hospital
🇬🇧Leicester, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
West Walk Surgery
🇬🇧Bristol, United Kingdom