A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
2018년 3월 6일 업데이트: 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.
연구 개요
연구 유형
중재적
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Cambridge, 영국, CB2 0GG
- GSK Investigational Site
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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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위약 비교기: 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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Number of subjects with Adverse Events (AEs): Part 1
기간: Up to Week 29
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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
기간: Up to Week 29
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Samples for clinical chemistry tests will be collected as a measure of safety
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Up to Week 29
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Number of subjects with abnormal hematology values: Part 1
기간: Up to Week 29
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Samples for clinical hematology tests will be collected as a measure of safety
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Up to Week 29
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Number of subjects with abnormal urine analysis values: Part 1
기간: Up to Week 29
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Samples for Urine analysis tests will be collected as a measure of safety
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Up to Week 29
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Number of subjects with abnormal findings of body temperature: Part 1
기간: Up to Week 29
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Body temperature 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 blood pressure: Part 1
기간: 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
기간: 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.
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Up to Week 29
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Number of subjects with abnormal findings of respiratory rate: Part 1
기간: Up to Week 29
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Respiratory rate 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 Electrocardiogram (ECG) findings: Part 1
기간: Up to Week 29
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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
기간: Up to Week 35
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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 35
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Number of subjects with abnormal clinical chemistry values: Part 2
기간: Up to Week 35
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Samples for clinical chemistry tests will be collected as a measure of safety
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Up to Week 35
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Number of subjects with abnormal hematology values: Part 2
기간: Up to Week 35
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Samples for clinical hematology tests will be collected as a measure of safety
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Up to Week 35
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Number of subjects with abnormal urine analysis values: Part 2
기간: Up to Week 35
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Samples for Urine analysis tests will be collected as a measure of safety
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Up to Week 35
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Number of subjects with abnormal findings of body temperature: Part 2
기간: Up to Week 35
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Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 35
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Number of subjects with abnormal findings of blood pressure: Part 2
기간: Up to Week 35
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SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 35
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Number of subjects with abnormal findings of pulse rate: Part 2
기간: 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
기간: Up to Week 35
|
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 35
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Number of subjects with abnormal ECG findings: Part 2
기간: Up to Week 35
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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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Plasma concentration of GSK2618960: Part 1
기간: 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
기간: 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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Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
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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
기간: 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.
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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
기간: 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.
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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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AUC of GSK2618960: Part 2
기간: 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
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Number of incidences of ADA formation: Part 2
기간: Up to Week 35
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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 35
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Number of titres of ADA: Part 2
기간: Up to Week 35
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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 35
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Time to onset of ADA: Part 2
기간: Up to Week 35
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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 35
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Number of incidences of ADA neutralization: Part 2
기간: Up to Week 35
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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 35
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Receptor occupancy (RO) on circulating T cells: Part 2
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2017년 9월 19일
기본 완료 (실제)
2017년 10월 12일
연구 완료 (예상)
2017년 10월 12일
연구 등록 날짜
최초 제출
2017년 6월 19일
QC 기준을 충족하는 최초 제출
2017년 8월 1일
처음 게시됨 (실제)
2017년 8월 4일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 3월 7일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 3월 6일
마지막으로 확인됨
2018년 3월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 201579
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
자가면역질환에 대한 임상 시험
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GSK2618960 2 mg/kg에 대한 임상 시험
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Poitiers University Hospital완전한
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Hoag Memorial Hospital PresbyterianDa Zen Theranostics Inc초대로 등록
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