Clinical trial NCT05660850: A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough
Official title: A Phase IIa, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Refractory Cough (CRC) With Non-atopic Asthma
CRC With Atopic Asthma
Unexplained Chronic Cough
CRC With Chronic Obstructive Pulmonary Disease
CRC With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in cough frequency per hour, assessed objectively over 24 hours (24-hour OCC) using VitaloJAK cough recorder
timeFrame: From baseline to Day 14
Secondary outcomes:
measure: Change in the severity of cough, as assessed through the use of the patient-reported cough severity VAS score
timeFrame: From baseline to Day 14
measure: Change in the severity of cough, as assessed through the use of the patient-reported cough severity NRS score
timeFrame: From baseline to Day 14
measure: Change in cough hypersensitivity to mannitol, measured as the CDR to mannitol
timeFrame: From baseline to Day 14
measure: Change in mannitol-induced AHR
timeFrame: From baseline to Day 14
measure: Incidence and severity of adverse events, with severity determined according to the DAIDS toxicity grading scale
timeFrame: From baseline to Day 14
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Southern California Institute For Respiratory
state: California
city: Northridge
country: United States
facility: California Medical Research Associates, Inc.
state: California
city: Miami
country: United States
facility: Pioneer Clinical Studies
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: DuBois
country: United States
facility: Clinical Research Associates Of Central Pa , Llc
state: Pennsylvania
city: Greenville
country: United States
facility: ADAC Research PA
state: South Carolina
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting, Inc.
state: Texas
city: Bellingham
country: United States
facility: Bellingham Asthma, Allergy & Immunology
state: Washington
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital; Eastern Clinical Research Unit
state: Victoria
city: Spearwood
country: Australia
facility: TrialsWest Pty Ltd
state: Western Australia
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Quebec
country: Canada
facility: Diex Recherche - Québec - HyperCore - PPDS
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Bristol
country: United Kingdom
facility: West Walk Surgery
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Kingston-upon-Hull
country: United Kingdom
facility: Hull York Medical School Centre for Cardiovascular and Metabolic Research
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Queen Anne Street Medical Centre
Study officials:
affiliation: Genetech
name: Clinical Trials
role: STUDY_DIRECTOR
References: