- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT03239600
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
6. März 2018 aktualisiert von: GlaxoSmithKline
A Two Part Phase IIa Study, to Evaluate the Safety and Tolerability, Pharmacokinetics, Proof of Mechanism and Potential for Efficacy of an Anti-IL-7 Receptor-α Monoclonal Antibody (GSK2618960) in the Treatment of Primary Sjögren's Syndrome
This study aims to evaluate the safety, tolerability and PK of repeat dose administration of GSK2618960 in the treatment of pSS.
The study will contain two parts, Part I will be open label and Part II will be randomized, double-blind.
The minimum duration of Part I & Part II of the study will be 26 and 32 weeks respectively.
Studienübersicht
Status
Zurückgezogen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
-
Cambridge, Vereinigtes Königreich, CB2 0GG
- GSK Investigational Site
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 70 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Part I and Part II: Male and females aged 18-70
- Part I and Part II: pSS diagnosis according to the American-European Consensus Group Criteria
- Part I and Part II: Documented previous biopsy evidence of salivary gland inflammation consistent with pSS and/or documented history of anti-Ro and/or anti-La antibodies
- Part II: Has any of the following abnormalities at screening: hypergammaglobulinaemia [serum Immunoglobulin G (IgG) greater than or equal to 16 gram per liter (g/L); Presence of Rheumatoid factor (RF); Anti Nuclear Antibodies (ANA) titer greater than or equal to 320:1.
- Stimulated whole salivary flow greater than 0.1 milliliter per minute (mL/min) at screening.
- Symptomatic oral dryness greater than or equal to 5 out of 10 on Visual Analogue Scale (VAS) scale and/or Schirmer test less than 10 millimeter (mm) at screening.
Exclusion Criteria:
- Part I and II: Secondary Sjögren's Syndrome
- Part I and II: Receiving cyclophosphamide, other biologic, immunosuppressive or immunomodulatory treatments
- Part I and II: Active infections, or history of recurrent infections
- Part I and II: History of significant medical illness
- Part I and II: History of lymphoma
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
|
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
MTX dose between 7.5 to 15 mg will be administered in tablet form once in a week till last dose of GSK2618960 to all subjects in Part I and Part II.
|
Placebo-Komparator: Part II: Placebo
Placebo will be administered IV with MTX
|
MTX dose between 7.5 to 15 mg will be administered in tablet form once in a week till last dose of GSK2618960 to all subjects in Part I and Part II.
Placebo solution will be administered by IV infusion.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Number of subjects with Adverse Events (AEs): Part 1
Zeitfenster: Up to Week 29
|
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
|
Up to Week 29
|
Number of subjects with abnormal clinical chemistry values: Part 1
Zeitfenster: Up to Week 29
|
Samples for clinical chemistry tests will be collected as a measure of safety
|
Up to Week 29
|
Number of subjects with abnormal hematology values: Part 1
Zeitfenster: Up to Week 29
|
Samples for clinical hematology tests will be collected as a measure of safety
|
Up to Week 29
|
Number of subjects with abnormal urine analysis values: Part 1
Zeitfenster: Up to Week 29
|
Samples for Urine analysis tests will be collected as a measure of safety
|
Up to Week 29
|
Number of subjects with abnormal findings of body temperature: Part 1
Zeitfenster: Up to Week 29
|
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 29
|
Number of subjects with abnormal findings of blood pressure: Part 1
Zeitfenster: Up to Week 29
|
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 29
|
Number of subjects with abnormal findings of pulse rate: Part 1
Zeitfenster: Up to Week 29
|
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 29
|
Number of subjects with abnormal findings of respiratory rate: Part 1
Zeitfenster: Up to Week 29
|
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 29
|
Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
Zeitfenster: Up to Week 29
|
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
|
Up to Week 29
|
Number of subjects with AEs: Part 2
Zeitfenster: Up to Week 35
|
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
|
Up to Week 35
|
Number of subjects with abnormal clinical chemistry values: Part 2
Zeitfenster: Up to Week 35
|
Samples for clinical chemistry tests will be collected as a measure of safety
|
Up to Week 35
|
Number of subjects with abnormal hematology values: Part 2
Zeitfenster: Up to Week 35
|
Samples for clinical hematology tests will be collected as a measure of safety
|
Up to Week 35
|
Number of subjects with abnormal urine analysis values: Part 2
Zeitfenster: Up to Week 35
|
Samples for Urine analysis tests will be collected as a measure of safety
|
Up to Week 35
|
Number of subjects with abnormal findings of body temperature: Part 2
Zeitfenster: Up to Week 35
|
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 35
|
Number of subjects with abnormal findings of blood pressure: Part 2
Zeitfenster: Up to Week 35
|
SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 35
|
Number of subjects with abnormal findings of pulse rate: Part 2
Zeitfenster: Up to Week 35
|
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 35
|
Number of subjects with abnormal findings of respiratory rate: Part 2
Zeitfenster: Up to Week 35
|
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 35
|
Number of subjects with abnormal ECG findings: Part 2
Zeitfenster: Up to Week 35
|
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
|
Up to Week 35
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Plasma concentration of GSK2618960: Part 1
Zeitfenster: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
Zeitfenster: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
Zeitfenster: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Area under the curve (AUC) of GSK2618960: Part 1
Zeitfenster: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Blood samples will be collected prior to start and at the end of infusion at indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
|
Number of incidences of Anti-drug antibody (ADA) formation: Part 1
Zeitfenster: Up to Week 29
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 29
|
Number of titres of ADA: Part 1
Zeitfenster: Up to Week 29
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 29
|
Time to onset of ADA: Part 1
Zeitfenster: Up to Week 29
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 29
|
Number of incidences of ADA neutralization: Part 1
Zeitfenster: Up to Week 29
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 29
|
Plasma concentration of GSK2618960 : Part 2
Zeitfenster: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters
|
Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Cmax of GSK2618960: Part 2
Zeitfenster: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Cmin of GSK2618960: Part 2
Zeitfenster: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
AUC of GSK2618960: Part 2
Zeitfenster: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Blood samples will be collected prior to start and at the end of infusion at indicated time points and will be analyzed for PK parameters.
|
Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
|
Number of incidences of ADA formation: Part 2
Zeitfenster: Up to Week 35
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 35
|
Number of titres of ADA: Part 2
Zeitfenster: Up to Week 35
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 35
|
Time to onset of ADA: Part 2
Zeitfenster: Up to Week 35
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 35
|
Number of incidences of ADA neutralization: Part 2
Zeitfenster: Up to Week 35
|
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 35
|
Receptor occupancy (RO) on circulating T cells: Part 2
Zeitfenster: Up to Week 35
|
Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.
|
Up to Week 35
|
Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
Zeitfenster: Up to Week 35
|
Blood samples will be collected from subjects at indicated time points to measure phosphorylation of STAT 5 in response to ex vivo IL-7 stimulation.
|
Up to Week 35
|
Change from Baseline in Focus score: Part 2
Zeitfenster: Up to Day 29
|
Salivary glands for immunohistochemistry analysis will be evaluated for general appearance and total inflammatory infiltrate (focus score).
Salivary gland biopsy will be performed at Baseline and blood samples will be collected at indicated time points.
|
Up to Day 29
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
19. September 2017
Primärer Abschluss (Tatsächlich)
12. Oktober 2017
Studienabschluss (Voraussichtlich)
12. Oktober 2017
Studienanmeldedaten
Zuerst eingereicht
19. Juni 2017
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
1. August 2017
Zuerst gepostet (Tatsächlich)
4. August 2017
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
7. März 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
6. März 2018
Zuletzt verifiziert
1. März 2018
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Immunsystems
- Augenkrankheiten
- Gelenkerkrankungen
- Erkrankungen des Bewegungsapparates
- Rheumatische Erkrankungen
- Bindegewebserkrankungen
- Arthritis
- Stomatognathe Erkrankungen
- Mundkrankheiten
- Erkrankungen des Tränenapparates
- Arthritis, Rheuma
- Xerostomie
- Speicheldrüsenerkrankungen
- Syndrome des trockenen Auges
- Autoimmunerkrankungen
- Sjögren-Syndrom
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Inhibitoren der Nukleinsäuresynthese
- Enzym-Inhibitoren
- Antirheumatika
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Dermatologische Wirkstoffe
- Reproduktionskontrollmittel
- Abtreibungsmittel, nichtsteroidal
- Abtreibungsmittel
- Folsäure-Antagonisten
- Methotrexat
Andere Studien-ID-Nummern
- 201579
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Nein
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
Klinische Studien zur Autoimmunerkrankungen
-
Yale UniversityNational Institute of Allergy and Infectious Diseases (NIAID); National Institutes... und andere MitarbeiterAbgeschlossen
-
University Hospital, Basel, SwitzerlandSwiss National Science Foundation; Kantonsspital Baselland Bruderholz; HEMMI Stiftung...RekrutierungAutoimmun | Entzündliche StörungDeutschland, Schweiz
-
Assiut UniversityUnbekanntAutoimmun-Uveitis
-
Ahvaz Jundishapur University of Medical SciencesAbgeschlossenLupus erythematodes, systemisch | AutoimmunIran, Islamische Republik
-
Second Affiliated Hospital, School of Medicine,...Changxing People's Hospital; First People's Hospital of Yuhang; Taizhou Women...UnbekanntThyreoiditis, AutoimmunChina
-
Nanjing Medical UniversityUnbekannt
-
TaiwanJ Pharmaceuticals Co., LtdUnbekanntAutoimmunhepatitis
-
Cugene Inc.RekrutierungSystemischer Lupus erythematodes | Autoimmun | SLE (systemischer Lupus)Vereinigte Staaten
-
Rock Creek Pharmaceuticals, Inc.AbgeschlossenThyreoiditis, AutoimmunVereinigte Staaten
-
Northwestern UniversityIcahn School of Medicine at Mount Sinai; Mount Sinai Hospital, New YorkAbgeschlossenAutoimmunhepatitisVereinigte Staaten
Klinische Studien zur GSK2618960 2 mg/kg
-
Keymed Biosciences Co.LtdNoch keine RekrutierungSystemischer Lupus erythematodes
-
Genor Biopharma Co., Ltd.RekrutierungHER2-positiver BrustkrebsChina
-
Crucell Holland BVNational Institute of Allergy and Infectious Diseases (NIAID)AbgeschlossenGrippeVereinigte Staaten
-
Crucell Holland BVNational Institute of Allergy and Infectious Diseases (NIAID)AbgeschlossenGrippeVereinigte Staaten
-
Xentria, Inc.AbgeschlossenGesunde TeilnehmerVereinigte Staaten
-
Serum Institute of India Pvt. Ltd.PPDAbgeschlossen
-
GlaxoSmithKlineBeendetMultiple Sklerose, schubförmig remittierendVereinigtes Königreich
-
Poitiers University HospitalAbgeschlossen
-
Corvus Pharmaceuticals, Inc.BeendetCovid-19Vereinigte Staaten, Kolumbien, Spanien, Kanada, Peru, Brasilien, Italien, Argentinien, Chile, Deutschland, Mexiko, Ukraine
-
Acceleron Pharma Inc. (a wholly owned subsidiary...Beendet