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

6. mars 2018 oppdatert av: 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.

Studieoversikt

Status

Tilbaketrukket

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Storbritannia
      • Cambridge, Storbritannia, CB2 0GG
        • GSK Investigational Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 70 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

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

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

GlaxoSmithKline

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

19. september 2017

Primær fullføring (Faktiske)

12. oktober 2017

Studiet fullført (Forventet)

12. oktober 2017

Datoer for studieregistrering

Først innsendt

19. juni 2017

Først innsendt som oppfylte QC-kriteriene

1. august 2017

Først lagt ut (Faktiske)

4. august 2017

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

7. mars 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

6. mars 2018

Sist bekreftet

1. mars 2018

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 201579

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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