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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT05934526
Ethics application status
Date submitted
28/06/2023
Date registered
7/07/2023

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 24 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 = 475 meters during Screening prior to randomization.
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 OR PVR = 800 dyne s/cm^5.
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 48 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) = 15 mmHg.
8. Treatment with at least one allowed background PAH disease-specific medication prior to Screening.

1. Subjects receiving treatment with endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, guanylate cyclase stimulators, and/or prostacyclin analogues or prostacyclin receptor agonists are eligible only if on a stable dose for at least 12 weeks prior to and throughout Screening.
2. Subjects receiving treatment with sotatercept are eligible only if on a stable dose of sotatercept (WINREVAIR™) for at least 24 weeks prior to and throughout Screening, with a RHC performed during Screening (or within 2 weeks prior to Screening).
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 systolic blood pressure > 160 mm Hg or 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 veno-occlusive disease (PVOD).
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 or uncontrolled symptomatic coronary 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. Prior/concurrent treatment with tyrosine kinase inhibitors or activin signaling inhibitors:

1. Tyrosine kinase inhibitors, other than Janus kinase inhibitors approved for systemic autoimmune rheumatic diseases, within 12 weeks prior to Screening.
2. Activin signaling inhibitors within 5 half-lives 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. Bleeding 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.

g. CTD-APAH

h. Concomitant use of sotatercept.
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 12 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
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 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
- Hobart
Recruitment postcode(s) [4] 0 0
- Kingswood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
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Connecticut
Country [5] 0 0
United States of America
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District of Columbia
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United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
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Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
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Kansas
Country [11] 0 0
United States of America
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Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Missouri
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Nebraska
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New Mexico
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United States of America
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Texas
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Utah
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Virginia
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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
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Argentina
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Córdoba
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Argentina
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Quilmes
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Argentina
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Rosario
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Argentina
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Río Cuarto
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Argentina
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Santa Fe
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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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Brazil
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Porto Alegre
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Canada
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Ontario
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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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Montpellier
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Poitiers
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Vandœuvre-lès-Nancy
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Dresden
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Gießen
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Germany
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Greifswald
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Germany
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Halle
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Germany
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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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Homburg
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Germany
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Munich
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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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Bologna
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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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Pavia
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Italy
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Rome
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Japan
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Suita
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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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Mexico
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Mexico City
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Mexico
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Monterrey
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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
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Portugal
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Porto
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Portugal
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Vila Nova De Gaia
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Puerto Rico
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Guaynabo
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Romania
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Bucharest
Country [96] 0 0
Romania
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Cluj-Napoca
Country [97] 0 0
Romania
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Târgu-Mures
Country [98] 0 0
Serbia
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Belgrade
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Majadahonda
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Spain
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Marbella
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Spain
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Palma De Mallorca
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Spain
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Salamanca
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Spain
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Santander
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Spain
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Sevilla
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Spain
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Toledo
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Spain
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Valencia
Country [110] 0 0
United Kingdom
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Cambridge
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Clydebank
Country [112] 0 0
United Kingdom
State/province [112] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05934526