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

Autoimmune Diseases Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03239600
• Other study ID #: 201579
• Status: Withdrawn
• Phase: Phase 2
• First received: June 19, 2017
• Last updated: March 6, 2018
• Start date: September 19, 2017
• Est. completion date: October 12, 2017

Study information

• Verified date: March 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 12, 2017
• Est. primary completion date: October 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Sjogren's Syndrome

Intervention

Drug:
• GSK2618960 2 mg/kg
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
• Placebo
Placebo solution will be administered by IV infusion.
• 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.

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with Adverse Events (AEs): Part 1	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
Primary	Number of subjects with abnormal clinical chemistry values: Part 1	Samples for clinical chemistry tests will be collected as a measure of safety	Up to Week 29
Primary	Number of subjects with abnormal hematology values: Part 1	Samples for clinical hematology tests will be collected as a measure of safety	Up to Week 29
Primary	Number of subjects with abnormal urine analysis values: Part 1	Samples for Urine analysis tests will be collected as a measure of safety	Up to Week 29
Primary	Number of subjects with abnormal findings of body temperature: Part 1	Body temperature will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 29
Primary	Number of subjects with abnormal findings of blood pressure: Part 1	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
Primary	Number of subjects with abnormal findings of pulse rate: Part 1	Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 29
Primary	Number of subjects with abnormal findings of respiratory rate: Part 1	Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 29
Primary	Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1	Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine	Up to Week 29
Primary	Number of subjects with AEs: Part 2	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
Primary	Number of subjects with abnormal clinical chemistry values: Part 2	Samples for clinical chemistry tests will be collected as a measure of safety	Up to Week 35
Primary	Number of subjects with abnormal hematology values: Part 2	Samples for clinical hematology tests will be collected as a measure of safety	Up to Week 35
Primary	Number of subjects with abnormal urine analysis values: Part 2	Samples for Urine analysis tests will be collected as a measure of safety	Up to Week 35
Primary	Number of subjects with abnormal findings of body temperature: Part 2	Body temperature will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 35
Primary	Number of subjects with abnormal findings of blood pressure: Part 2	SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 35
Primary	Number of subjects with abnormal findings of pulse rate: Part 2	Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 35
Primary	Number of subjects with abnormal findings of respiratory rate: Part 2	Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.	Up to Week 35
Primary	Number of subjects with abnormal ECG findings: Part 2	Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine	Up to Week 35
Secondary	Plasma concentration of GSK2618960: Part 1	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
Secondary	Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1	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
Secondary	Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1	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
Secondary	Area under the curve (AUC) of GSK2618960: Part 1	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
Secondary	Number of incidences of Anti-drug antibody (ADA) formation: Part 1	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
Secondary	Number of titres of ADA: Part 1	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
Secondary	Time to onset of ADA: Part 1	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
Secondary	Number of incidences of ADA neutralization: Part 1	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
Secondary	Plasma concentration of GSK2618960 : Part 2	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
Secondary	Cmax of GSK2618960: Part 2	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
Secondary	Cmin of GSK2618960: Part 2	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
Secondary	AUC of GSK2618960: Part 2	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
Secondary	Number of incidences of ADA formation: Part 2	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
Secondary	Number of titres of ADA: Part 2	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
Secondary	Time to onset of ADA: Part 2	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
Secondary	Number of incidences of ADA neutralization: Part 2	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
Secondary	Receptor occupancy (RO) on circulating T cells: Part 2	Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.	Up to Week 35
Secondary	Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2	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
Secondary	Change from Baseline in Focus score: Part 2	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