GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH)

• ClinicalTrials.gov Identifier: NCT04456998
• Recruitment Status: Completed
• First Posted: July 7, 2020
• Last Update Posted: February 9, 2023
• Sponsor: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Information provided by (Responsible Party): Gossamer Bio Inc. ( GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. )

Tracking Information

• First Submitted Date: June 30, 2020
• First Posted Date: July 7, 2020
• Last Update Posted Date: February 9, 2023
• Actual Study Start Date: December 14, 2020
• Actual Primary Completion Date: October 17, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2020)

Change from Baseline to Week 24 in Pulmonary Vascular Resistance (PVR) [ Time Frame: Baseline, 24 weeks ]

Change in PVR using right heart catheterization (RHC)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 30, 2020)

Change From Baseline to Week 24 on the Six-Minute Walk Test (6MWT) [ Time Frame: Baseline, 24 weeks ]

Change in distance achieved on the 6MWT (Δ6MWD)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH)
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Study to Evaluate the Efficacy and Safety of Oral Inhalation of GB002 for the Treatment of WHO Group 1 Pulmonary Arterial Hypertension (PAH)
• Brief Summary: The primary objective for this trial is to determine the effect of GB002 (seralutinib) on improving pulmonary hemodynamics in subjects with World Health Organization (WHO) Group 1 PAH who are Functional Class (FC) II and III. The secondary objective for this trial is to determine the effect of GB002 (seralutinib) on improving exercise capacity in this population.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Subjects, investigators, other site personnel, and Sponsor (and/or designee) personnel who are directly involved in the conduct of the study, collection of the data, and analysis of the final safety and efficacy results will remain blinded to treatment assignments until after the completion of the study and the database has been locked.

Primary Purpose: Treatment

• Condition: Pulmonary Artery Hypertension

Intervention

• Drug: GB002 (seralutinib)
  Capsule containing GB002 (seralutinib)
• Drug: Placebo
  Matching capsule containing placebo
• Device: Generic Dry Powder Inhaler
  Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery

Study Arms

• Experimental: GB002 (seralutinib)
  GB002 (seralutinib) inhaled orally twice per day (BID) over 24 weeks
  Interventions:

  • Drug: GB002 (seralutinib)
  • Device: Generic Dry Powder Inhaler
• Placebo Comparator: Placebo
  Placebo inhaled orally BID over 24 weeks
  Interventions:

  • Drug: Placebo
  • Device: Generic Dry Powder Inhaler

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 23, 2022): 86
• Original Estimated Enrollment (submitted: June 30, 2020): 80
• Actual Study Completion Date: November 1, 2022
• Actual Primary Completion Date: October 17, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. A current diagnosis of symptomatic PAH classified by one of the following:

   1. Idiopathic PAH (IPAH) or heritable pulmonary arterial hypertension (HPAH).
   2. PAH associated with connective tissue disease (CTD-APAH).
   3. PAH associated with anorexigen or methamphetamine use.
   4. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.
2. 6MWD ≥ 150 meters and ≤ 550 meters at screening.
3. WHO FC II or III symptomatology.
4. Treatment with standard of care PAH background therapies.

5. Documentation of cardiac catheterization within the screening period that is consistent with the diagnosis of PAH and meeting all the following criteria, to be confirmed by a central hemodynamic core laboratory:

   1. Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (at rest), AND
   2. PVR ≥ 400 dyne•sec/cm5, AND
   3. Pulmonary capillary wedge pressure (PCWP) or left ventricular-end diastolic pressure (LVEDP) ≤12 mm Hg if PVR ≥400 to <500 dyne∙sec/cm5 OR
   4. PCWP or LVEDP ≤15 mmHg if PVR ≥500 dyne∙sec/cm5

6. Pulmonary function tests (PFTs) at screening with the following criteria met:

   1. Forced expiratory volume in 1 second (FEV1) divided by the forced vital capacity (FVC) ≥70%;
   2. Total lung capacity (TLC) or FVC ≥ 70% predicted

Exclusion Criteria:

1. Evidence of chronic thromboembolic disease or acute pulmonary embolism as assessed by ventilation-perfusion (V/Q) scan, computed tomography (CT)-angiogram, or pulmonary angiogram prior to screening.
2. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during screening visit after a period of rest.
3. Systolic blood pressure < 90 mm Hg during screening and baseline visits.
4. WHO Pulmonary Hypertension Group 2-5.
5. Human immunodeficiency virus (HIV)-associated PAH.
6. History of left-sided heart disease and/or clinically significant cardiac disease.
7. Untreated severe obstructive sleep apnea.
8. History of atrial septostomy within 180 days prior to screening.
9. Pulmonary venous occlusive disease (PVOD).
10. Subjects with a history of portopulmonary hypertension or portal hypertension due to cirrhosis classified as Child-Pugh Class A or higher; or baseline ALT or AST > 2 x ULN or Total Bilirubin ≥ 2 x ULN.
11. History of malignancy within 5 years prior to screening.
12. History of a potentially life-threatening cardiac arrhythmia with an ongoing risk.
13. Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg; history intracranial hemorrhage).
14. Chronic renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) at screening or requires dialytic therapy or hemofiltration.
15. Hemoglobin (Hgb) concentration < 8.5 g/dL at screening.
16. Evidence of active HIV, Hepatitis B or Hepatitis C, or tuberculosis (TB) infections.
17. Inhaled prostanoids; these drugs may be withdrawn ≥ 4 weeks prior to or at screening, if clinically indicated.
18. Use of oral anticoagulants (ie, warfarin or NOAC) at randomization.
19. Requirement of intravenous (IV) inotropes (ie, levosimendan, dopamine, dobutamine, milrinone, norepinephrine) other than an IV prostanoid within 4 weeks of screening.
20. Prior participation in GB002 studies and/or prior treatment with GB002.
21. Currently participating in or has participated in a study of an investigational agent or has used an investigational device for the treatment of PAH within 4 weeks prior to screening.
22. Current use of inhaled tobacco and/or inhaled marijuana.
23. Current alcohol use disorder as defined by DSM-5 and/or positive test for drugs of abuse (amphetamines, methamphetamines, cocaine, phencyclidine [PCP]).
24. Subjects with a history of severe milk protein allergy. In addition, subjects with known intolerance or hypersensitivity to lactose who, in the opinion of the investigator, may experience severe symptoms following the ingestion of lactose.
25. QTcF of > 480 msec recorded on a screening or baseline ECG or receiving concurrent treatment with medications that prolong QT interval.
26. Have any other condition or reason that, in the opinion of the Investigator or Medical Monitor, would prohibit the subject from participating in the study.

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Czechia, France, Germany, Serbia, Spain, United Kingdom, United States
• Removed Location Countries: Israel

Administrative Information

• NCT Number: NCT04456998
• Other Study ID Numbers: GB002-2101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gossamer Bio Inc. ( GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Richard Aranda; Gossamer Bio Inc.

• PRS Account: Gossamer Bio Inc.
• Verification Date: November 2022