A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
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
Przegląd badań
Status
Status
Warunki
Warunki
Interwencja / Leczenie
Interwencja / Leczenie
Typ studiów
Typ studiów
Faza
Faza
- Faza 2
Kontakty i lokalizacje
Lokalizacje studiów
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Cambridge, Zjednoczone Królestwo, CB2 0GG
- GSK Investigational Site
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Kryteria uczestnictwa
Kryteria kwalifikacji
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Poczwórny
Liczba ramion
Broń i interwencje
Grupa uczestników / ArmGrupa uczestników / Arm |
Interwencja / LeczenieInterwencja / Leczenie |
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Eksperymentalny: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
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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.
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Komparator placebo: Part II: Placebo
Placebo will be administered IV with MTX
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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.
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Co mierzy badanie?
Podstawowe miary wyniku
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Number of subjects with Adverse Events (AEs): Part 1
Ramy czasowe: 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.
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Up to Week 29
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Number of subjects with abnormal clinical chemistry values: Part 1
Ramy czasowe: Up to Week 29
|
Samples for clinical chemistry tests will be collected as a measure of safety
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Up to Week 29
|
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Number of subjects with abnormal hematology values: Part 1
Ramy czasowe: 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
Ramy czasowe: Up to Week 29
|
Samples for Urine analysis tests will be collected as a measure of safety
|
Up to Week 29
|
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Number of subjects with abnormal findings of body temperature: Part 1
Ramy czasowe: Up to Week 29
|
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
|
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Number of subjects with abnormal findings of blood pressure: Part 1
Ramy czasowe: 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.
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Up to Week 29
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Number of subjects with abnormal findings of pulse rate: Part 1
Ramy czasowe: Up to Week 29
|
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
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Number of subjects with abnormal findings of respiratory rate: Part 1
Ramy czasowe: Up to Week 29
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Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
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Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
Ramy czasowe: Up to Week 29
|
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
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Up to Week 29
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Number of subjects with AEs: Part 2
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
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Number of subjects with abnormal ECG findings: Part 2
Ramy czasowe: Up to Week 35
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Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
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Up to Week 35
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Miary wyników drugorzędnych
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Plasma concentration of GSK2618960: Part 1
Ramy czasowe: 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
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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.
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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
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Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
Ramy czasowe: 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
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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.
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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
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Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
Ramy czasowe: 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
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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.
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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
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Area under the curve (AUC) of GSK2618960: Part 1
Ramy czasowe: 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
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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.
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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
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Number of incidences of Anti-drug antibody (ADA) formation: Part 1
Ramy czasowe: Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Number of titres of ADA: Part 1
Ramy czasowe: Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Time to onset of ADA: Part 1
Ramy czasowe: Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Number of incidences of ADA neutralization: Part 1
Ramy czasowe: Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Plasma concentration of GSK2618960 : Part 2
Ramy czasowe: 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
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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
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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
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Cmax of GSK2618960: Part 2
Ramy czasowe: 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
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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.
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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
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Cmin of GSK2618960: Part 2
Ramy czasowe: 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
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AUC of GSK2618960: Part 2
Ramy czasowe: 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
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Number of incidences of ADA formation: Part 2
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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.
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Up to Week 35
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Receptor occupancy (RO) on circulating T cells: Part 2
Ramy czasowe: Up to Week 35
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Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.
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Up to Week 35
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Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
Ramy czasowe: Up to Week 35
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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.
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Up to Week 35
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Change from Baseline in Focus score: Part 2
Ramy czasowe: Up to Day 29
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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.
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Up to Day 29
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Współpracownicy i badacze
Sponsor
Sponsor
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Rozpoczęcie studiów
Zakończenie podstawowe (Rzeczywisty)
Zakończenie podstawowe
Ukończenie studiów (Oczekiwany)
Ukończenie studiów
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Pierwszy wysłany
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia wysłana aktualizacja
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
- Choroby układu odpornościowego
- Choroby oczu
- Choroby stawów
- Choroby układu mięśniowo-szkieletowego
- Choroby reumatyczne
- Choroby tkanki łącznej
- Artretyzm
- Choroby Stomatognatyczne
- Choroby jamy ustnej
- Choroby aparatu łzowego
- Zapalenie stawów, reumatoidalne
- Kserostomia
- Choroby gruczołów ślinowych
- Zespoły suchego oka
- Choroby Autoimmunologiczne
- Zespół Sjogrena
- Fizjologiczne skutki leków
- Molekularne mechanizmy działania farmakologicznego
- Inhibitory syntezy kwasów nukleinowych
- Inhibitory enzymów
- Środki przeciwreumatyczne
- Antymetabolity, przeciwnowotworowe
- Antymetabolity
- Środki przeciwnowotworowe
- Środki immunosupresyjne
- Czynniki immunologiczne
- Środki dermatologiczne
- Środki kontroli reprodukcji
- Środki poronne, niesteroidowe
- Środki poronne
- Antagoniści kwasu foliowego
- Metotreksat
Inne numery identyfikacyjne badania
Inne numery identyfikacyjne badania
- 201579
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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