Clinical trial NCT03239600: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Autoimmune Diseases
Keywords: Anti-IL-7 Receptor-alpha Monoclonal Antibody
Safety
GSK2618960
Primary Sjögren's Syndrome
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-08-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel assignment where in Part II of the study, randomized subject will receive GSK2618960 and placebo drug simultaneously.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with Adverse Events (AEs): Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal clinical chemistry values: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal hematology values: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal urine analysis values: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal findings of body temperature: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal findings of blood pressure: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal findings of pulse rate: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal findings of respiratory rate: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
timeFrame: Up to Week 29
measure: Number of subjects with AEs: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal clinical chemistry values: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal hematology values: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal urine analysis values: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal findings of body temperature: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal findings of blood pressure: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal findings of pulse rate: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal findings of respiratory rate: Part 2
timeFrame: Up to Week 35
measure: Number of subjects with abnormal ECG findings: Part 2
timeFrame: Up to Week 35
Secondary outcomes:
measure: Plasma concentration of GSK2618960: Part 1
timeFrame: 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
measure: Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
timeFrame: 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
measure: Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
timeFrame: 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
measure: Area under the curve (AUC) of GSK2618960: Part 1
timeFrame: 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
measure: Number of incidences of Anti-drug antibody (ADA) formation: Part 1
timeFrame: Up to Week 29
measure: Number of titres of ADA: Part 1
timeFrame: Up to Week 29
measure: Time to onset of ADA: Part 1
timeFrame: Up to Week 29
measure: Number of incidences of ADA neutralization: Part 1
timeFrame: Up to Week 29
measure: Plasma concentration of GSK2618960 : Part 2
timeFrame: 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
measure: Cmax of GSK2618960: Part 2
timeFrame: 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
measure: Cmin of GSK2618960: Part 2
timeFrame: 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
measure: AUC of GSK2618960: Part 2
timeFrame: 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
measure: Number of incidences of ADA formation: Part 2
timeFrame: Up to Week 35
measure: Number of titres of ADA: Part 2
timeFrame: Up to Week 35
measure: Time to onset of ADA: Part 2
timeFrame: Up to Week 35
measure: Number of incidences of ADA neutralization: Part 2
timeFrame: Up to Week 35
measure: Receptor occupancy (RO) on circulating T cells: Part 2
timeFrame: Up to Week 35
measure: Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
timeFrame: Up to Week 35
measure: Change from Baseline in Focus score: Part 2
timeFrame: Up to Day 29
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: