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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: GB002
* Drug: Placebo
* Device: Generic Dry Powder Inhaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (males and females) aged 18 to 75 years (inclusive) with pulmonary arterial hypertension (PAH) (Main study) A current diagnosis of symptomatic PAH classified by one of the following (Main and OLE study): Idiopathic (IPAH) or heritable pulmonary arterial hypertension (HPAH) PAH associated with one of the following connective tissue diseases (CTDs): systemic sclerosis, rheumatoid arthritis, mixed CTD or overlap syndrome, or systemic lupus erythematosus PAH associated with anorexigen or methamphetamine use World Health Organization (WHO)/New York Heart Association (NYHA) functional class II-IV symptomatology (Main study) Exclusion Criteria: Clinically significant systemic hypertension or hypotension (Main and OLE study) History of left-sided heart disease and/or clinically significant cardiac disease (Main and OLE study) 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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 |