Pulmonary Arterial Hypertension
Conditions
Brief summary
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).
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.
Interventions
DRUGGB002
GB002 low dose or high dose for inhalation
DRUGPlacebo
Placebo for inhalation
Generic dry powder inhaler for GB002 or Placebo delivery
Sponsors
GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Clinical site investigators, study personnel, and study subjects will be blinded to treatment assignment; however, the Sponsor will be unblinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment-Related Adverse Events GB002 (Main study) | Up to 45 days | To evaluate the safety and tolerability of GB002 |
| Number of participants with Treatment-Related Adverse Events GB002 (OLE study) | Up to 200 days | To evaluate the long-term safety and tolerability and efficacy of GB002 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of GB002 (Main study) | 14 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 |
| Changes from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) (OLE study) | 169 days |
| Pharmacokinetics: Maximum Concentration (Cmax) of GB002 (Main study) | 14 days |
Countries
United Kingdom, United States
Outcome results
None listed