The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001227381
Ethics application status
Approved
Date submitted
16/08/2017
Date registered
23/08/2017
Date last updated
19/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I trial to evaluate the safety and tolerability of GDC-0214 in healthy volunteers and patients with mild asthma
Scientific title
A Phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GDC-0214 conducted in three parts: a single ascending dose study in healthy volunteers, a multiple-ascending dose study in healthy volunteers, and a proof of activity study in patients with mild asthma.
Secondary ID [1] 292618 0
NONE
Universal Trial Number (UTN)
Trial acronym
N/A
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Asthma 304304 0
Condition category
Condition code
Respiratory 303661 303661 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For Part A, healthy volunteers will receive a single inhaled dose of GDC-0214 or placebo. The starting dose will be 0.15 mg inhaled. A total of 5 sequential dose cohorts are planned: Cohort A, B, C, D, and E. Doses will be escalated based on safety, tolerability, and available PK data.

For Part B, healthy volunteers will receive an inhaled dose of GDC-0214 or placebo once or twice daily for a total of 14 days. A total of 4 sequential dose cohorts are planned: Cohort F, G, H, and I. Doses will be escalated based on safety, tolerability, and available PK data. Daily dose will not exceed those evaluated in Part A.

For Part C, subject with mild asthma will receive an inhaled dose of GDC-0214 or placebo once or twice daily for a total of 14 days. A total of 3 sequential dose cohorts are planned. Doses will be escalated based on safety, tolerability, and available PK data. Dose and duration will not exceed those evaluated in Part B.

For parts A, B and C all dosing will be done in clinic under the supervision of qualified medical staff.

A Safety Monitoring committee that will include at minimum the Medical Monitor, a drug safety scientist, and a biostatistician from the Sponsor; and will be responsible for dose-escalation decisions, with consent from the investigator.


Intervention code [1] 298835 0
Treatment: Drugs
Comparator / control treatment
Placebo treatment is an inhaled capsule containing lactose monohydrate with no active substance.
Control group
Placebo

Outcomes
Primary outcome [1] 303021 0
The primary objective of this study is to characterize the safety profile associated with GDC-0214. This will be measured through observation and the severity of any adverse events, change from baseline in vital signs, and laboratory test results
Timepoint [1] 303021 0
Adverse events will be reported after any occurrence after the first dose. Vital signs will be collected at each study visit for part A (visit days 1 through 15). For part B and C they will be collected on visit days (1-17, 21, 28, 35 and 42).
Secondary outcome [1] 337712 0
To characterize the PK profile of GDC 0214, Plasma concentrations of GDC-0214 will be assessed and pharmacokinetic parameters such as through AUC, tmax, Cmax, and half-life will be calculated.
Timepoint [1] 337712 0
To characterize the PK profile of GDC 0214 16 plasma samples will be assessed for GDC-0214 concentrations during the course of the SAD in order to sufficiently characterize PK parameters such as Tmax, Cmax,t1/2, and AUC. Individual PK parameters will not be assessed at specific time points since they require the totality of the data. PK will be collected on Day 1 (Pre-dose, 5 min (0.08h), 0.25h, 0.5h, 1h, 2h, 4h, 8h, and 12h). On Day 2 (24h and 36h post-dose). On Day 3 (48hr post-dose). On Day 4 (72h post-dose) and anytime during visit days 6, 10 and 15.

Eligibility
Key inclusion criteria
Key Inclusion Criteria for Healthy Volunteers • Signed Informed Consent Form
• Age 18-65 years
• Body mass index of 18-37 kg/m2
• Weight of 50-120 kg
• In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs.
• First forced expiratory volume (FEV1) >70 % predicted
• Forced vital capacity (FVC) >2.0 L
• Ability to demonstrate sufficient inspiratory effort using the inhaler training
• Ability to comply with the study protocol, including all study procedures
• Agreement to remain abstinent or use contraceptive methods

Key Inclusion Criteria for Patients with Mild Asthma • Signed Informed Consent Form
• Age 18-65 years
• Body mass index of 18-37 kg/m2
• Weight of 50-120 kg
• Documented physician-diagnosed mild asthma for at least 6 months prior to screening, defined as: Asthma that is controlled with as-needed reliever medication with or without a leukotriene receptor antagonist
• No use of inhaled corticosteroids within 60 days prior to initiation of study drug
• FeNO >40 ppb at screening and at pre-randomization visit
• No clinically significant ECG abnormalities
• Clinical laboratory evaluations should be within the reference range for the test laboratory unless deemed not clinically significant by the investigator and Sponsor.
• FEV1 >70 % predicted
• FVC >2.0 L
• Ability to demonstrate sufficient inspiratory effort using the inhaler training device
• Ability to comply with the study protocol, including all study procedures
• Agreement to remain abstinent or use contraceptive methods
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Key Exclusion Criteria for Healthy Volunteers
Subjects who meet any of the following criteria will be excluded from Parts A and B:
• History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, gastrointestinal, urologic, neurologic, or psychiatric disorders, in the investigator’s judgment
• History of nasal polyposis or nasal polyps identified during screening physical examination
• History of anaphylaxis, hypersensitivity, or significant drug allergies
• History of severe hypersensitivity to milk proteins
• History or presence of an abnormal ECG that is clinically significant
• Any medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the subject’s safe participation in and completion of the study
• Illicit drug or alcohol abuse within 12 months prior to initiation of study drug
• Positive alcohol screen at screening or pre-randomization
• Recent history of smoking within the 35 days prior to initiation of study drug
• Smokers not able to pass the tobacco-related screening and who cannot refrain from smoking during the study
• Positive urine test for selected drugs of abuse at screening
• Pregnant or breastfeeding, or intending to become pregnant during the study
Women of childbearing potential must have a negative pregnancy test result at screening or pre-randomization.
• Use of any prescription medications and products within 7 days prior to initiation of study drug and throughout the study
• Use of a investigational drug or recent participation in an investigational study
• Positive for hepatitis panel at screening

Exclusion Criteria for Patients with Mild Asthma
Subjects who meet any of the following criteria will be excluded from Part C:
• Any of the exclusion criteria for healthy volunteers above
• Lack of asthma control defined as respiratory symptoms requiring use of a reliever inhaler (e.g., 2 puffs of SABA) more than twice a day on a regular basis within 4 weeks prior to initiation of study drug (not including reliever medication used to prevent symptoms)
• Recent asthma exacerbation requiring oral corticosteroid use or urgent medical care for asthma within 12 weeks prior to initiation of study drug
• Any asthma-related history, symptoms, or findings that precludes the subject’s safe participation in and completion of the study in the investigator’s judgment

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 9136 0
New Zealand
State/province [1] 9136 0

Funding & Sponsors
Funding source category [1] 297247 0
Commercial sector/Industry
Name [1] 297247 0
Genentech, Inc.
Address [1] 297247 0
1 DNA Way
South San Francisco CA, 94080
Country [1] 297247 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
1 DNA Way
South San Francisco CA, 94080
Country
United States of America
Secondary sponsor category [1] 296218 0
None
Name [1] 296218 0
Address [1] 296218 0
Country [1] 296218 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298367 0
Ethics committee address [1] 298367 0
Ethics committee country [1] 298367 0
Date submitted for ethics approval [1] 298367 0
24/08/2017
Approval date [1] 298367 0
31/10/2017
Ethics approval number [1] 298367 0

Summary
Brief summary
The purpose of this study is to test the safety of GDC-0214 at different dose levels and to find out what effects, good or bad, GDC-0214 has on volunteers. This study will be conducted in three parts. Part A and Part B will be in healthy volunteers between the ages of 18 and 65 years and Part C in patients with mild asthma between the ages of 18 and 65 years.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76842 0
Dr Chris Wynne
Address 76842 0
Christchurch Clinical Studies Trust
31 Tuam Street, Christchurch, 8011
Country 76842 0
New Zealand
Phone 76842 0
+64 3 372 9478
Fax 76842 0
Email 76842 0
research@ccst.co.nz
Contact person for public queries
Name 76843 0
Mrs Ryan Ceniceros
Address 76843 0
Genentech, Inc.
1 DNA Way, South San Francisco CA 94080
Country 76843 0
United States of America
Phone 76843 0
+1-650-238-8619
Fax 76843 0
Email 76843 0
ceniceros.ryan@gene.com
Contact person for scientific queries
Name 76844 0
Dr Hubert Chen
Address 76844 0
Genentech, Inc.
1 DNA Way, South San Francisco, CA 94080
Country 76844 0
United States of America
Phone 76844 0
+1 650-225-4619
Fax 76844 0
Email 76844 0
chen.hubert@gene.com

No data has been provided for results reporting
Summary results
Not applicable