- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT03239600
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
tiistai 6. maaliskuuta 2018 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Tila
Peruutettu
Ehdot
Interventio / Hoito
Opintotyyppi
Interventio
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Cambridge, Yhdistynyt kuningaskunta, CB2 0GG
- GSK Investigational Site
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta - 70 vuotta (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: 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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Placebo Comparator: 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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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
---|---|---|
Number of subjects with Adverse Events (AEs): Part 1
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
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Number of subjects with abnormal findings of blood pressure: Part 1
Aikaikkuna: Up to Week 29
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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
Aikaikkuna: Up to Week 29
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Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 29
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Number of subjects with abnormal findings of respiratory rate: Part 1
Aikaikkuna: 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
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Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
Aikaikkuna: 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
Aikaikkuna: 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
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Number of subjects with abnormal clinical chemistry values: Part 2
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Up to Week 35
|
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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
---|---|---|
Plasma concentration of GSK2618960: Part 1
Aikaikkuna: 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
Aikaikkuna: 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.
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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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
|
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
Aikaikkuna: 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.
|
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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
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Receptor occupancy (RO) on circulating T cells: Part 2
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Tiistai 19. syyskuuta 2017
Ensisijainen valmistuminen (Todellinen)
Torstai 12. lokakuuta 2017
Opintojen valmistuminen (Odotettu)
Torstai 12. lokakuuta 2017
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Maanantai 19. kesäkuuta 2017
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Tiistai 1. elokuuta 2017
Ensimmäinen Lähetetty (Todellinen)
Perjantai 4. elokuuta 2017
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Keskiviikko 7. maaliskuuta 2018
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Tiistai 6. maaliskuuta 2018
Viimeksi vahvistettu
Torstai 1. maaliskuuta 2018
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Immuunijärjestelmän sairaudet
- Silmäsairaudet
- Nivelsairaudet
- Tuki- ja liikuntaelinten sairaudet
- Reumaattiset sairaudet
- Sidekudostaudit
- Niveltulehdus
- Stomatognaattiset sairaudet
- Suun sairaudet
- Kyynellaitteiston sairaudet
- Niveltulehdus, nivelreuma
- Kserostomia
- Sylkirauhasten sairaudet
- Kuivan silmän oireyhtymät
- Autoimmuunisairaudet
- Sjogrenin syndrooma
- Huumeiden fysiologiset vaikutukset
- Farmakologisen vaikutuksen molekyylimekanismit
- Nukleiinihapposynteesin estäjät
- Entsyymin estäjät
- Reumaattiset aineet
- Antimetaboliitit, antineoplastiset
- Antimetaboliitit
- Antineoplastiset aineet
- Immunosuppressiiviset aineet
- Immunologiset tekijät
- Dermatologiset aineet
- Lisääntymistä säätelevät aineet
- Raskaudenkeskeytysaineet, ei-steroidiset
- Abortiagentit
- Foolihappoantagonistit
- Metotreksaatti
Muut tutkimustunnusnumerot
- 201579
Lääke- ja laitetiedot, tutkimusasiakirjat
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