A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
2018年3月6日 更新者：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.
調査の概要
研究の種類
介入
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Cambridge、イギリス、CB2 0GG
- GSK Investigational Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～70年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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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プラセボコンパレーター：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of subjects with Adverse Events (AEs): Part 1
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：Up to Week 35
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Samples for Urine analysis tests will be collected as a measure of safety
|
Up to Week 35
|
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Number of subjects with abnormal findings of body temperature: Part 2
時間枠：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
時間枠：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
時間枠：Up to Week 35
|
Pulse 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 findings of respiratory rate: Part 2
時間枠：Up to Week 35
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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 35
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Number of subjects with abnormal ECG findings: Part 2
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Plasma concentration of GSK2618960: Part 1
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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AUC of GSK2618960: Part 2
時間枠：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 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
時間枠：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
|
|
Number of titres of ADA: Part 2
時間枠：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
|
|
Time to onset of ADA: Part 2
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2017年9月19日
一次修了 (実際)
2017年10月12日
研究の完了 (予想される)
2017年10月12日
試験登録日
最初に提出
2017年6月19日
QC基準を満たした最初の提出物
2017年8月1日
最初の投稿 (実際)
2017年8月4日
学習記録の更新
投稿された最後の更新 (実際)
2018年3月7日
QC基準を満たした最後の更新が送信されました
2018年3月6日
最終確認日
2018年3月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 201579
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
GSK2618960 2 mg/kgの臨床試験
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University of Ioannina募集
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GlaxoSmithKline終了しました
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Rockefeller UniversityBrigham and Women's Hospital; Weill Medical College of Cornell University; University of Cologne完了
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GlaxoSmithKline完了