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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05934526




Registration number
NCT05934526
Ethics application status
Date submitted
28/06/2023
Date registered
7/07/2023
Date last updated
23/05/2024

Titles & IDs
Public title
Efficacy and Safety of Seralutinib in Adult Subjects With PAH (PROSERA)
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Inhalation of Seralutinib for the Treatment of Pulmonary Arterial Hypertension (PAH)
Secondary ID [1] 0 0
2023-503614-80-00
Secondary ID [2] 0 0
GB002-3101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Seralutinib
Treatment: Devices - Generic Dry Powder Inhaler

Placebo Comparator: Placebo - Placebo inhaled orally twice daily (BID) up to 48 weeks

Experimental: Seralutinib 90 mg - Seralutinib inhaled orally BID up to 48 weeks


Treatment: Drugs: Placebo
Matching capsule containing placebo

Treatment: Drugs: Seralutinib
Capsule containing seralutinib

Treatment: Devices: Generic Dry Powder Inhaler
Generic dry powder inhaler for seralutinib or placebo delivery
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in distance achieved on the six-minute walk test (6MWT), six-minute walk distance (?6MWD) from baseline to Week 24
Timepoint [1] 0 0
Baseline to 24 weeks
Secondary outcome [1] 0 0
Time to first event of Clinical Worsening from first dose of Investigational Product (IP) through end of study
Timepoint [1] 0 0
Baseline to 48 weeks
Secondary outcome [2] 0 0
Proportion of subjects who achieve all of the following components of clinical improvement at Week 24, in the absence of clinical worsening:
Timepoint [2] 0 0
Baseline to 24 weeks
Secondary outcome [3] 0 0
Change in NT-proBNP from baseline to Week 24
Timepoint [3] 0 0
Baseline to 24 weeks
Secondary outcome [4] 0 0
Proportion of subjects with = 1 point decrease from baseline in US Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score at Week 24
Timepoint [4] 0 0
Baseline to 24 weeks
Secondary outcome [5] 0 0
Proportion of subjects with each of the Clinical Worsening Outcomes:
Timepoint [5] 0 0
Baseline to 52 weeks
Secondary outcome [6] 0 0
Proportion of subjects who improve from baseline in WHO FC or maintain WHO FC II
Timepoint [6] 0 0
Baseline to 48 weeks
Secondary outcome [7] 0 0
Change in PAH-SYMPACT™ from baseline to Week 24
Timepoint [7] 0 0
Baseline to 24 weeks
Secondary outcome [8] 0 0
Change in Euro-QoL - 5 Dimensions - 5 Levels (EQ-5D-5L) from baseline to Week 24
Timepoint [8] 0 0
Baseline to 24 weeks
Secondary outcome [9] 0 0
Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs (SAEs), and treatment-emergent adverse events of special interest (AESIs)
Timepoint [9] 0 0
Baseline to 52 weeks

Eligibility
Key inclusion criteria
1. Adult subjects aged 18 to 75 years.

2. Body mass index (BMI) = 17 kg/m^2 and = 40 kg/m^2.

3. Diagnosis of PAH classified by one of the following:

1. Idiopathic PAH (IPAH) or heritable PAH (HPAH).

2. PAH associated with connective tissue disease (CTD-APAH); PAH associated with
anorexigen or PAH associated with methamphetamine use.

3. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year
after surgical repair.

4. 6MWDs = 150 meters and = 450 meters at Screening.

5. WHO FC II or III.

6. US Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2
Risk Score = 5 OR NT-proBNP = 300 ng/L.

7. Cardiac catheterization within the screening period, or a standard of care right heart
catheterization (RHC) (with pressure wave forms available for review) up to 24 weeks
prior to Screening.

1. Mean pulmonary arterial pressure (mPAP) > 20 mmHg (at rest), AND

2. Pulmonary vascular resistance (PVR) = 400 dyne·s/cm^5, AND

3. Pulmonary capillary wedge pressure (PCWP) or left ventricle end-diastolic
pressure (LVEDP) = 12 mmHg if PVR = 400 to < 500 dyne·s/cm^5 OR PCWP or LVEDP =
15 mmHg if PVR = 500 dyne·s/cm^5.

8. Treatment with at least one allowed background PAH disease-specific medication prior
to Screening, and on stable regimen and doses for at least 12 weeks.

9. Pulmonary function tests (PFTs) at Screening or completed no more than 12 weeks prior
to Screening.

10. Women of childbearing potential (WOCBP) must have a negative pregnancy test at
Screening and on Day 1 before first administration of Investigational Product (IP).

11. WOCBP who are not abstinent and intend to be sexually active with a non-sterilized
male partner must be willing to use a highly effective method of contraception from
consent through 30 days following the last administration of IP.

12. Male subjects: Non-sterilized male subjects who are not abstinent and intend to be
sexually active with a female partner of childbearing potential must use a male condom
from consent through 90 days after the last dose of IP.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Evidence of chronic thromboembolic disease or acute pulmonary embolism.

2. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >
160 mm Hg or sitting diastolic blood pressure > 100 mm Hg.

3. Systolic blood pressure < 90 mm Hg during Screening.

4. WHO Pulmonary Hypertension Group 2 - 5.

5. Human immunodeficiency virus (HIV)-associated PAH, schistosomiasis associated PAH, PAH
associated with portal hypertension, or pulmonary venous-occlusive disease (POVD).

6. Recent history of left-sided heart disease and/or clinically significant cardiac
disease within 48 weeks of Screening.

7. Left ventricular ejection fraction (LVEF) = 50% within 24 weeks of Screening.

8. Hemodynamically significant valvular heart disease.

9. History of atrial septostomy.

10. Uncontrolled atrial fibrillation or paroxysmal atrial fibrillation.

11. Untreated severe obstructive sleep apnea.

12. Hepatic dysfunction defined as Child-Pugh Class A or higher, or as evidenced by one of
the following at Screening: alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) > 2 x upper limit of normal (ULN) or total bilirubin = 2 x ULN.

13. Severe acute or chronic medical or laboratory abnormality that may increase the risk
associated with study participation or IP administration (eg, history of intracranial
hemorrhage, recurrent syncope).

14. Any musculoskeletal disease, injury, or any other disease that limits evaluation of
6MWT.

15. Initiation of an exercise program for cardiopulmonary rehabilitation within 12 weeks
prior to Screening or planned during the study.

16. Pregnant or nursing or intends to become pregnant during the duration of the study.

17. Body weight < 40 kg at Screening.

18. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m^2 Hemoglobin (Hgb)
concentration < 8.5 g/dL at Screening.

19. Evidence of active or latent Human immunodeficiency virus (HIV), Hepatitis B or
Hepatitis C, or tuberculosis (TB) infection at Screening.

20. Tyrosine kinase inhibitors within 12 weeks prior to Screening.

21. Requirement of IV inotropes (ie, levosimendan, dopamine, dobutamine, milrinone,
norepinephrine) or IV diuretics for more than 24 hours within 4 weeks prior to
Screening.

22. Subjects currently receiving oral anticoagulants (ie, warfarin/other vitamin K
antagonists or direct-acting oral anticoagulants [DOACs]) if any of the following
criteria are met:

a. History within 24 weeks of Screening of: i. Syncope, or ii. Symptomatic bleeding in
a critical area or organ iii. Intramuscular with compartment syndrome, or iv. Bleeding
causing a fall in hemoglobin levels of 1.24 mmol/L (20 g/L or greater) or more, or v.
Leading to a transfusion of 2 U or more of whole blood or red blood cells.

b. History of central nervous system pathology.

c. History of clinically significant (massive) hemoptysis.

d. If on warfarin/other vitamin K antagonist, uncontrolled International normalized
ratio (eg, INR > 3) as assessed.

e. Platelet count < 150 x 10^9/L at Screening.

f. Concomitant use of antiplatelet agents.

23. Prior participation in seralutinib studies and/or prior treatment with seralutinib.

24. 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 8 weeks or 5
half-lives of the investigational agent, whichever is longer, prior to Screening.

25. Current use of inhaled tobacco- or nicotine-containing products (including e-vapor
products) and/or inhaled marijuana.

26. Current alcohol use disorder based on the opinion of the Investigator, and/or a
positive test for drugs of abuse.

27. Subjects with a history of severe milk protein allergy or known intolerance to
lactose.

28. QT interval corrected for heart rate using Fridericia's formula (QTcF) of > 500 msec.

29. Have any other condition or reason that, in the opinion of the Investigator or in the
opinion of the Sponsor's Medical Monitor (MM) (or designee) in consultation with the
Investigator, would prohibit the subject from participating in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
350
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Macquarie University - North Ryde
Recruitment hospital [2] 0 0
St Vincent's Hospital - Melbourne
Recruitment hospital [3] 0 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment postcode(s) [2] 0 0
3065 - Melbourne
Recruitment postcode(s) [3] 0 0
- Kingswood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
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Ohio
Country [18] 0 0
United States of America
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Oklahoma
Country [19] 0 0
United States of America
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Oregon
Country [20] 0 0
United States of America
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Pennsylvania
Country [21] 0 0
United States of America
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South Carolina
Country [22] 0 0
United States of America
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Texas
Country [23] 0 0
United States of America
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Virginia
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United States of America
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Wisconsin
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Argentina
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Buenos Aires
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Argentina
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Corrientes
Country [27] 0 0
Argentina
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Córdoba
Country [28] 0 0
Argentina
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Quilmes
Country [29] 0 0
Argentina
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Rosario
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Argentina
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Río Cuarto
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Austria
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Linz
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Belgium
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Anderlecht
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Belgium
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Leuven
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Chile
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Region Metropolitana
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Chile
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Santiago
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Czechia
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Praha
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Aarhus
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Denmark
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Copenhagen
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France
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Le Kremlin-Bicêtre
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France
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Lille
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France
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Montpellier
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France
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Nice
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France
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Poitiers
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France
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Vandœuvre-lès-Nancy
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Germany
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Berlin
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Germany
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Dresden
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Gießen
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Germany
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Halle
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Hamburg
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Würzburg
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Greece
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Athens
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Greece
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Kallithéa
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Greece
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Thessaloníki
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Israel
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Haifa
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Israel
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Kfar Saba
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Israel
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Petach Tikva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Genova
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Italy
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Napoli
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Italy
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Rome
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Latvia
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Riga
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Lithuania
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Kaunas
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Netherlands
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Amsterdam
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Netherlands
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Rotterdam
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Poland
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Kraków
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Poland
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Otwock
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Portugal
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Coimbra
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Portugal
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Lisboa
Country [74] 0 0
Portugal
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Vila Nova De Gaia
Country [75] 0 0
Puerto Rico
State/province [75] 0 0
Guaynabo
Country [76] 0 0
Romania
State/province [76] 0 0
Bucharest
Country [77] 0 0
Romania
State/province [77] 0 0
Cluj-Napoca
Country [78] 0 0
Romania
State/province [78] 0 0
Târgu-Mures
Country [79] 0 0
Serbia
State/province [79] 0 0
Belgrade
Country [80] 0 0
Singapore
State/province [80] 0 0
Singapore
Country [81] 0 0
Spain
State/province [81] 0 0
Barcelona
Country [82] 0 0
Spain
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Madrid
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Spain
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Majadahonda
Country [84] 0 0
Spain
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Marbella
Country [85] 0 0
Spain
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Santander
Country [86] 0 0
Spain
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Sevilla
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Clydebank
Country [88] 0 0
United Kingdom
State/province [88] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GB002, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to determine the effect of seralutinib on improving
exercise capacity in subjects with WHO Group 1 PAH who are FC II or III. The secondary
objective for this trial is to determine time to clinical worsening.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05934526
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard Aranda, MD
Address 0 0
Gossamer Bio Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
GB002, Inc.
Address 0 0
Country 0 0
Phone 0 0
1-866-668-4083
Fax 0 0
Email 0 0
ClinicalTrials@gossamerbio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05934526