Clinical Study of Inhaled GB002 for Treatment of WHO Group I Pulmonary Arterial Hypertension (PAH)

A Phase 1b, Randomized, Subject- and Investigator-Blinded, Placebo-Controlled, Multi-Center Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Biomarkers of Inhaled GB002 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension (PAH)

This is a Phase 1B, randomized, participant- and investigator-blinded, placebo-controlled, multi-center clinical trial to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and biomarkers of inhaled GB002 in adults with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH).

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: GB002; Drug: Placebo; Device: Generic Dry Powder Inhaler

Detailed Description

The primary objective for this trial is to evaluate the safety and tolerability of GB002. The secondary objective for this trial is to evaluate the PK parameters of GB002. Exploratory objectives are to evaluate the PD readouts, change in WHO Group I functional class, and change in quality of life associated with GB002 treatment.

In this Phase 1B study, two dose levels of GB002 will be tested in adult participants with PAH. Four participants in cohort 1 will be randomized to receive up to two daily doses of either active drug or placebo, with 3 subjects receiving GB002 and 1 subject receiving placebo. An additional 4 participants (3 active and 1 placebo) may be added to cohort 1 at the discretion of the Data Review Committee (DRC). The dose and dosing interval (i.e., once daily or twice daily) for the second cohort will be determined by review of the safety, tolerability, and drug levels in the blood from cohort 1. Cohort 2 participants will also be randomized such that 6 subjects receive GB002 and 2 subjects receive placebo.

Eligible subjects who have completed the 2 week treatment period have the option to participate in a 24 week open label extension.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G814DY
    • Golden Jubilee National Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital, Imperial Healthcare NHS Trust
• United States
  • California
    • La Jolla, California, United States, 92037
      • UCSD Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Early Phase Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center Montefiore University Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Vitalink Research - Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult (males and females) aged 18 to 75 years (inclusive) with pulmonary arterial hypertension (PAH) (Main study)

2. A current diagnosis of symptomatic PAH classified by one of the following (Main and OLE study):

   1. Idiopathic (IPAH) or heritable pulmonary arterial hypertension (HPAH)

   2. PAH associated with one of the following connective tissue diseases (CTDs):

      systemic sclerosis, rheumatoid arthritis, mixed CTD or overlap syndrome, or systemic lupus erythematosus

   3. PAH associated with anorexigen or methamphetamine use
3. World Health Organization (WHO)/New York Heart Association (NYHA) functional class II-IV symptomatology (Main study)

Exclusion Criteria:

1. Clinically significant systemic hypertension or hypotension (Main and OLE study)
2. History of left-sided heart disease and/or clinically significant cardiac disease (Main and OLE study)
3. History of decompensated right heart failure within 30 days of screening (e.g., hospitalization for PAH or the need to add an additional PAH medication) (Main study)

NOTE: Additional inclusion/exclusion criteria may apply, per protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days	Drug: GB002; GB002 low dose or high dose for inhalation; Drug: Placebo; Placebo for inhalation; Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for GB002 or Placebo delivery
Experimental: Cohort 2; Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days	Drug: GB002; GB002 low dose or high dose for inhalation; Drug: Placebo; Placebo for inhalation; Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for GB002 or Placebo delivery
Experimental: Open Label Extension; Eligible subjects may participate in the Open Label Extension (OLE) study for a period of 24 weeks.	Drug: GB002; GB002 low dose or high dose for inhalation; Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for GB002 or Placebo delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment-Related Adverse Events GB002 (Main study)	To evaluate the safety and tolerability of GB002	Up to 45 days
Number of participants with Treatment-Related Adverse Events GB002 (OLE study)	To evaluate the long-term safety and tolerability and efficacy of GB002	Up to 200 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of GB002 (Main study)	14 days
Pharmacokinetics: Maximum Concentration (Cmax) of GB002 (Main study)	14 days
Pharmacokinetics: Area Under the Concentration Curve (AUC) of GB002 (Main study)	14 days
Changes from baseline in 6-Minute Walk Test (6MWT) (OLE study)	169 days
Changes from baseline in WHO Functional Class (OLE study)	197 days
Changes from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) (OLE study)	169 days
Changes from baseline in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) Quality of Life questionnaire (OLE study)	197 days
Changes from baseline in Right Ventricular function by imaging (OLE study)	169 days

Collaborators and Investigators

• Sponsor: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): May 5, 2021
• Study Completion (Actual): May 5, 2021

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: GB002-1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes