Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05660850




Registration number
NCT05660850
Ethics application status
Date submitted
7/11/2022
Date registered
21/12/2022
Date last updated
20/08/2024

Titles & IDs
Public title
A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough
Scientific 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
Secondary ID [1] 0 0
GA43590
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Refractory Cough (CRC) With Non-atopic Asthma 0 0
CRC With Atopic Asthma 0 0
Unexplained Chronic Cough 0 0
CRC With Chronic Obstructive Pulmonary Disease 0 0
CRC With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Asthma
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GDC-6599
Other interventions - GDC-6599-matching placebo
Diagnosis / Prognosis - Mannitol

Experimental: Part A: CRC Asthma atopic - 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

Experimental: Part A: CRC Asthma non-atopic - 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

Experimental: Part A: Unexplained Chronic Cough - 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

Experimental: Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease - 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.

Experimental: Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis - 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.


Treatment: Drugs: GDC-6599
GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets

Other interventions: GDC-6599-matching placebo
GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets

Diagnosis / Prognosis: Mannitol
Mannitol challenge tests will be performed during screening and at least 2.5 hours following study drug administration at Study Visits 2, 4, 5 and 7
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in cough frequency per hour, assessed objectively over 24 hours (24-hour OCC) using VitaloJAK cough recorder
Timepoint [1] 0 0
From baseline to Day 14
Secondary outcome [1] 0 0
Change in the severity of cough, as assessed through the use of the patient-reported cough severity VAS score
Timepoint [1] 0 0
From baseline to Day 14
Secondary outcome [2] 0 0
Change in the severity of cough, as assessed through the use of the patient-reported cough severity NRS score
Timepoint [2] 0 0
From baseline to Day 14
Secondary outcome [3] 0 0
Change in cough hypersensitivity to mannitol, measured as the CDR to mannitol
Timepoint [3] 0 0
From baseline to Day 14
Secondary outcome [4] 0 0
Change in mannitol-induced AHR
Timepoint [4] 0 0
From baseline to Day 14
Secondary outcome [5] 0 0
Incidence and severity of adverse events, with severity determined according to the DAIDS toxicity grading scale
Timepoint [5] 0 0
From baseline to Day 14

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/09/2024
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [2] 0 0
TrialsWest Pty Ltd - Spearwood
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
6163 - Spearwood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Belfast
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Bristol
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Edinburgh
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Kingston-upon-Hull
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Leicester
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Genetech
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GA43590, https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S.)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05660850