Clinical trial NCT03926793: Clinical Study of Inhaled GB002 for Treatment of WHO Group I Pulmonary Arterial Hypertension
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Gossamer Bio Inc.
Sponsor class: INDUSTRY
First posted: 2019-04-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Treatment-Related Adverse Events GB002 (Main study)
timeFrame: Up to 45 days
measure: Number of participants with Treatment-Related Adverse Events GB002 (OLE study)
timeFrame: Up to 200 days
Secondary outcomes:
measure: Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of GB002 (Main study)
timeFrame: 14 days
measure: Pharmacokinetics: Maximum Concentration (Cmax) of GB002 (Main study)
timeFrame: 14 days
measure: Pharmacokinetics: Area Under the Concentration Curve (AUC) of GB002 (Main study)
timeFrame: 14 days
measure: Changes from baseline in 6-Minute Walk Test (6MWT) (OLE study)
timeFrame: 169 days
measure: Changes from baseline in WHO Functional Class (OLE study)
timeFrame: 197 days
measure: Changes from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) (OLE study)
timeFrame: 169 days
measure: Changes from baseline in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) Quality of Life questionnaire (OLE study)
timeFrame: 197 days
measure: Changes from baseline in Right Ventricular function by imaging (OLE study)
timeFrame: 169 days
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Louisville
country: United States
facility: Norton Pulmonary Specialists
state: Kentucky
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke Early Phase Research
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Montefiore University Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: VitaLink Research - Anderson
state: South Carolina
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital, Imperial Healthcare NHS Trust
Study officials:
References: