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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 mis à jour par: 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.

Aperçu de l'étude

Statut

Retiré

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Royaume-Uni
      • Cambridge, Royaume-Uni, CB2 0GG
        • GSK Investigational Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
Médicament: GSK2618960 2 mg/kg
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
Médicament: 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.
Comparateur placebo: Part II: Placebo
Placebo will be administered IV with MTX
Médicament: 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.
Médicament: Placebo
Placebo solution will be administered by IV infusion.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of subjects with Adverse Events (AEs): Part 1
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Up to Week 35
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Up to Week 35

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Plasma concentration of GSK2618960: Part 1
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

GlaxoSmithKline

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

19 septembre 2017

Achèvement primaire (Réel)

12 octobre 2017

Achèvement de l'étude (Anticipé)

12 octobre 2017

Dates d'inscription aux études

Première soumission

19 juin 2017

Première soumission répondant aux critères de contrôle qualité

1 août 2017

Première publication (Réel)

4 août 2017

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

7 mars 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

6 mars 2018

Dernière vérification

1 mars 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 201579

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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