Phase 1A Safety Trial of Inhaled PK10571 (GB002)

NCT03473236 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: 4004002
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1A randomized double blind placebo controlled single ascending dose and multiple ascending dose trial of inhaled PK10571 (GB002) in healthy adult subjects.

Conditions

Safety Issues

Outcome Measures

Primary Outcomes (22)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious AE (SAE) is one that, in the view of either the investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. A TEAE is defined as any AE that has an onset on or after the first dose of study drug and before the end of study/end of treatment (EoS/ET) visit, or any pre-existing condition that has worsened in severity on or after the first dose of study drug and before the EoS/ET visit.

  SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days

• Number of Participants With Vital Sign Findings Reported as TEAEs

  Vital signs evaluated included blood pressure, pulse oximetry, respiratory rate, and temperature.

  SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days

• Number of Participants With Clinically Significant Findings in Physical Examinations

  Physical examination assessments included: physical exam for general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities, musculoskeletal and neurological.

  SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days

• Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation)

  12-lead electrocardiograms (ECG) assessments included heart rate, PR interval, QRS duration, QT interval, QTc interval, QTc interval corrected using Bazett's formula (QTcB), QTc interval corrected using Fridericia's formula (QTcF), RR interval.

  SAD: Baseline, Day 2, 24 hours; MAD: Baseline, Day 8, 24 hours

• Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests

  Pulmonary function tests included forced vital capacity; forced expiratory volume in 1 second (FEV1); forced expiratory flow 25%-75% (FEF25-75); percent predicted forced vital capacity; percent predicted FEV1; and percent predicted FEF25-75.

  SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days

• Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD

  CL/F is based on nominal (scheduled) dose.

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD

  Vz/F is based on nominal (scheduled) dose.

  0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD

  Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD

  Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD

  Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD

  Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Accumulation Ratio (Rac) for Cmax After Dose 1, MAD

  Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Rac for AUC0-24, MAD

  Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Rac for Ctrough, MAD

  Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: t1/2, MAD

  Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance at Steady-State (CLss/F), MAD

  Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

• PK Analysis of Inhaled GB002: Vz/F, MAD

  Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration

Other Outcomes (4)

• Change From Baseline in White Blood Cell Count

  SAD: from baseline to 11 days, MAD: from baseline to 35 days

• Change From Baseline in Hemoglobin

  SAD: from baseline to 11 days, MAD: from baseline to 35 days

• Change From Baseline in Kidney Function Parameters

  SAD: from baseline to 11 days, MAD: from baseline to 35 days

Study Arms (8)

Cohort 1A

EXPERIMENTAL

Dose 1 Single Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 2A

EXPERIMENTAL

Dose 2 Single Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 3A

EXPERIMENTAL

Dose 3 Single Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 4A

EXPERIMENTAL

Dose 4 Single Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 5A

EXPERIMENTAL

Dose 5 Single Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 1B

EXPERIMENTAL

Dose 1 Multiple Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 2B

EXPERIMENTAL

Dose 2 Multiple Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Cohort 3B

EXPERIMENTAL

Dose 3 Multiple Ascending Dose Protocol: within the cohort, 6 participants receive active drug (GB002) and 2 participants receive placebo.

Drug: GB002; Device: Generic Dry Powder Inhaler; Drug: Placebo

Interventions

GB002 DRUG

Inhaled GB002

Also known as: PK10571

Cohort 1A; Cohort 1B; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 5A

Generic Dry Powder Inhaler DEVICE

dry powder inhaler used for inhalation of active drug or placebo

Cohort 1A; Cohort 1B; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 5A

Placebo DRUG

Inhaled placebo

Cohort 1A; Cohort 1B; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 5A

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females (if unable to become pregnant)
• Age 18-55
• Body mass index (BMI) 18-32 kg/m\^2 and minimum weight of 50 kg (110 lbs)
• Non-smoker
• Ability to give informed consent
• Ability to remain in study unit for duration of study and return for outpatient visits
• Ability to use dry powder inhaler (DPI) effectively
• (See full protocol for additional details.)

You may not qualify if:

• Hospitalization within the 6 months prior to the first dose of study treatment
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results
• History or presence of active lung disease (i.e., asthma, chronic obstructive pulmonary disease \[COPD\], pulmonary fibrosis, hemoptysis, bronchiectasis) or prior intubation
• Currently uses an inhaler
• History or presence of heart disease (i.e., prior myocardial infarction \[MI\], coronary artery disease, heart failure, hypertension, pulmonary hypertension, valve disease, atrial fibrillation, other arrhythmia, or prolonged QT syndrome)
• History or presence of cancer (with the exception of basal cell skin cancer that has been effectively treated)
• History of diabetes mellitus
• History of thyroid disease other than hypothyroidism control with levothyroxine and documented normal thyroid-stimulating hormone (TSH)
• History of tuberculosis, Lyme disease, or other chronic or opportunistic infection.
• History of positive purified protein derivative (PPD) skin test, or positive PPD test at screening
• Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at screening or has been previously treated for hepatitis B, hepatitis C, or HIV infection
• History of smoking within the past 15 years
• Is a female with a positive pregnancy test result, or who has the ability to become pregnant, or who is lactating
• Has forced expiratory volume in 1 second (FEV1) less than 80% predicted, forced vital capacity (FVC) ˂80% predicted, or resting oxygen saturation less than 97% on room air at screening or baseline
• Upper respiratory infection within the 3 months prior to the first dose of medication

Sponsors & Collaborators

• GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.: lead
• Pulmokine Inc.: collaborator
• Worldwide Clinical Trials: collaborator

Study Sites (1)

Phase 1 Unit

San Antonio, Texas, 00000, United States

Location

Results Point of Contact

• Title: R. Aranda M.D. / Senior Vice President of Clinical Development
• Organization: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

raranda@gossamerbio.com

(858) 684-1300

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 22, 2018
• Study Start: September 6, 2017
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: June 9, 2020
• Results First Posted: February 17, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)