Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)

6. marts 2018 opdateret af: 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.

Studieoversigt

Status

Trukket tilbage

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
Medicin: GSK2618960 2 mg/kg
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
Medicin: Methotrexate
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
Medicin: Methotrexate
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.
Medicin: Placebo
Placebo solution will be administered by IV infusion.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of subjects with Adverse Events (AEs): Part 1
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Up to Week 35
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Up to Week 35

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Plasma concentration of GSK2618960: Part 1
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

GlaxoSmithKline

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

19. september 2017

Primær færdiggørelse (Faktiske)

12. oktober 2017

Studieafslutning (Forventet)

12. oktober 2017

Datoer for studieregistrering

Først indsendt

19. juni 2017

Først indsendt, der opfyldte QC-kriterier

1. august 2017

Først opslået (Faktiske)

4. august 2017

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

7. marts 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. marts 2018

Sidst verificeret

1. marts 2018

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 201579

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Autoimmune sygdomme

Kliniske forsøg med GSK2618960 2 mg/kg

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Djibouti

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner