台灣臨床試驗主持人資料庫|TPIDB

適應症

克隆氏症患者的透壁癒合和疾病改善

試驗目的

主要目標 •依據第48 週的核磁共振活性指數(MaRIA)，評估guselkumab 在達到透壁癒合方面的療效。基於MaRIA 的次要目標 •評估guselkumab 在第16 週和第96 週在達到透壁癒合方面的療效。 •評估guselkumab 達到嚴重發炎病灶透壁癒合的療效。 •依據MaRIA 和內視鏡，評估guselkumab 在達到透壁癒合方面的療效。 •根據MaRIA 和臨床資料，評估guselkumab在達到透壁癒合方面的療效。 •根據MaRIA 和生物標記，評估guselkumab在達到透壁癒合方面的療效。 •根據MaRIA 和內視鏡檢查和臨床資料，評估guselkumab 在達到透壁癒合方面的療效。 •根據MaRIA，評估guselkumab 在達到透壁緩解方面的療效。 •根據MaRIA 和根據SES-CD 的內視鏡緩解，評估guselkumab 在達到透壁緩解方面的療效。 •依據整體簡易MaRIA 分數，評估guselkumab 隨時間的療效。 •評估guselkumab 在依據MRE 評估的透壁緩解而維持疾病控制時消除皮質類固醇需求方面的療效。基於IUS 的次要目標 •評估guselkumab 在依據腸道超音波(IUS) 達到透壁（分節和整體）反應方面的療效。 •依據IUS，評估guselkumab 在達到透壁緩解方面的療效。 •依據國際腸道超音波節段活性分數(IBUS-SAS)，評估guselkumab 隨時間的療效。 •評估guselkumab 在依據IUS 評估的透壁緩解而維持疾病控制時消除皮質類固醇需求方面的療效 •依據IUS 隨時間所評估的BWT，評估guselkumab 的療效。 •依據CD 簡易IUS 分數(SUS-CD)，評估guselkumab 隨時間的療效。 •依據IUS 隨時間所評估的BWT，評估guselkumab 的療效。依據內視鏡檢查的次要目標 •評估guselkumab 在整個試驗期間達到內視鏡反應的療效。 •評估guselkumab 在整個試驗期間達到內視鏡緩解的療效。 •依據SES-CD，評估guselkumab 隨時間的療效。 •評估guselkumab 在依據內視鏡緩解而維持疾病控制時消除皮質類固醇需求方面的療效。 •評估guselkumab 在達到腸道黏膜內視鏡癒合方面的療效依據臨床資料的次要目標 •評估試驗期間guselkumab 在達到臨床緩解方面的療效。 •評估試驗期間guselkumab 在達到臨床反應方面的療效。 •評估guselkumab 在依據臨床緩解而維持疾病控制時消除皮質類固醇需求方面的療效。 •依據CDAI 評估guselkumab 隨時間的療效。依據PRO 的次要目標 •評估guselkumab 對於健康相關生活品質(HRQoL) 和PRO 的影響。依據生物標記的次要目標 •依據生物標記結果，評估guselkumab 的療效。安全性目的 •評估guselkumab 的整體安全性

藥品名稱

靜脈點滴注射劑
注射劑
預充填式注射劑

主成份

guselkumab

劑型

242
270
230

劑量

10 mg/mL, 200 mg/vial FVP(IV)
100mg/1mL guselkumab (pre-filled syringe)
100 mg/mL, 2 mL fill

評估指標

在第48 週時，所有腸道節段中達到
MaRIA ＜11 的參與者比例。

主要納入條件

Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1. Male or female (according to their reproductive organs and functions assigned by
chromosomal complement) aged 18 years (or the legal age of consent in the jurisdiction
in which the study is taking place) or over.
Type of Participant and Disease Characteristics
2. Has luminal Crohn’s disease of at least 3 months duration (defined as a minimum of
12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by
radiography, histology, and/or endoscopy.
3. Has clinically active Crohn’s disease, defined as a baseline CDAI score ≥220 but ≤450
and either:
a. Mean daily SF count ≥4, based on the unweighted CDAI component of the number
of liquid or very soft stools
OR
b. Mean daily AP score ≥2, based on the unweighted CDAI component of AP
4. Active transmural activity in at least one segment (segmental MaRIA ≥ 11)
5. a. Has demonstrated inadequate response/intolerance to conventional therapy
(Appendix 3: Definitions of Inadequate Response to or Intolerance of Corticosteroids
or 6-MP/AZA/MTX and Corticosteroid Dependence) and is naïve to, or exposed to but
never failed, advanced therapies16
OR
b. Has previously demonstrated lack of initial response (ie, primary non‐responders),
responded initially but then lost response with continued therapy (ie, secondary
non-responders), or was intolerant to a maximum of 1 class of advanced therapies at a
dose approved for the treatment of Crohn's disease (ie, JAK inhibitors, infliximab,
adalimumab, certolizumab pegol, vedolizumab, ustekinumab, or approved biosimilars
for these agents). To note, the proportion of participants that have failed to IL12-23
(eg, ustekinumab) will be limited to around 20% of this advanced therapy non-
responders/intolerant group included in the study (see Section 4.1). Please refer to
Appendix 4: Definition of Inadequate Initial Response, Loss of Response, or
Intolerance to TNF Antagonist Therapies (Infliximab, Adalimumab, or Certolizumab
Pegol), Vedolizumab, or Ustekinumab for details. Inadequate response to JAK
inhibitors is based on the clinical judgment of the investigator.
17
6. Adheres to the following requirements for concomitant medication for the treatment of
Crohn's disease. The following medications are permitted if doses meeting the
requirements listed below are stable or have been discontinued prior to baseline and
within the timeframes specified below:
a. Oral corticosteroids at a prednisone‐equivalent dose at or below 20 mg/day, or
6 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate, and on stable
dosing for at least 2 weeks or if recently discontinued, must have been stopped for at
least 2 weeks.
b. If the participant was on 5-ASA therapy at baseline, they must have been on a stable
dose for at least 2 weeks, or if recently discontinued, they must have stopped at least 2
weeks before baseline. Participants may continue the 5-ASA treatment if ongoing at
baseline.
c. Conventional immunomodulators (ie, AZA, 6‐MP, or MTX) for at least 12 weeks and
have been on a stable dose for at least 4 weeks or if recently discontinued, must have
been stopped for at least 4 weeks.
d. If receiving antibiotics as a primary treatment of luminal Crohn's disease, doses must
be stable for at least 3 weeks or if recently discontinued, must have been stopped for at
least 3 weeks.
e. If receiving enteral nutrition as a primary treatment for Crohn’s disease, must have
been receiving for at least 2 weeks or if recently discontinued, must have been stopped
for at least 2 weeks.
f. Must agree not to receive a Bacille Calmette-Guérin (BCG) vaccination during the
study and for 12 weeks after receiving the last dose of study intervention.
g. Must agree not to receive a live virus or live bacterial vaccination during the study and
for 12 weeks after receiving the last dose of study intervention.
Note: Participant who requires treatment for latent TB must complete the appropriate course of
TB therapy.
7. Screening laboratory test results within the following parameters, and if 1 or more of
the laboratory parameters is out of range, a single retest of laboratory values is
permitted during the approximate 3-week screening period:
a. Hemoglobin ≥8.0 g/dL
b. White blood cells (WBCs) ≥ 3.0 x 103 /μL
c. Neutrophils ≥1.5 x 103 /μL
d. Platelets ≥100 x 103 /μL
e. Serum creatinine ≤1.5 mg/dL.
f. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 using the Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
g. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations
must be ≤2 times the upper limit of normal range for the laboratory conducting the test.
h. Direct (conjugated) bilirubin ≤1.5 x ULN.
Must be otherwise healthy on the basis of clinical laboratory tests performed at screening. If the
results of the serum chemistry panel, including liver enzymes hematology, or urinalysis are
outside the normal reference ranges, the participant may be included only if the investigator
judges the abnormalities or deviations from normal to be not clinically significant or to be
appropriate and reasonable for the population under study. This determination must be recorded
in the participant's source documents and initialed by the investigator.
.
Sex and Contraceptive/Barrier Requirements
8. A female participant of childbearing potential all female participants must have a
negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) at
screening.
9. A female participant must be (as defined in Appendix 8: Contraceptive and Barrier
Guidance)
a. Not of childbearing potential
OR
b. Of childbearing potential and practicing a highly effective method of contraception
(failure rate of ＜1% per year when used consistently and correctly) and agrees to remain
on a highly effective method while receiving study intervention and until 150 days after
last dose - the end of relevant systemic exposure. The investigator must evaluate the
potential for contraceptive method failure (eg, noncompliance, recently initiated) in
relationship to the first dose of study intervention. Examples of highly effective
methods of contraception are located in Appendix 8: Contraceptive and Barrier
Guidance.
Note: If a participant’s childbearing potential changes after start of the study (eg, a
premenarchal woman experiences menarche) or the risk of pregnancy changes (eg, a
woman who is not heterosexually active becomes active), a woman must begin using a
highly effective method of contraception,
18
as described throughout the inclusion and
exclusion criteria.
10. A male participant must wear a condom when engaging in any activity that allows for
passage of ejaculate to another person for 90 days after the last dose of azathioprine
guselkumab or placebo. Male participants must also be advised of the benefit for a
female partner to use a highly effective method of contraception as condom may break
or leak.
11. Woman of childbearing potential or man capable of fathering children must be using
adequate birth control measures. Donation of Ova, oocytes and sperm for the purpose
of assisted reproduction during the study and for a period of 12 weeks after the last
administration of study interventions are prohibited.
Informed Consent
12. Must sign an informed consent form (ICF) (or their legally acceptable representative
when permitted by local regulations must sign) indicating that he/she understands the
purpose of, and procedures required for, the study and is willing to participate.
13. Be willing and able to adhere to all specified requirements including but not limited to
completion of assessments, adherence to visit schedule etc, as specified in this protocol.

主要排除條件

Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1. Male or female (according to their reproductive organs and functions assigned by
chromosomal complement) aged 18 years (or the legal age of consent in the jurisdiction
in which the study is taking place) or over.
Type of Participant and Disease Characteristics
2. Has luminal Crohn’s disease of at least 3 months duration (defined as a minimum of
12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by
radiography, histology, and/or endoscopy.
3. Has clinically active Crohn’s disease, defined as a baseline CDAI score ≥220 but ≤450
and either:
a. Mean daily SF count ≥4, based on the unweighted CDAI component of the number
of liquid or very soft stools
OR
b. Mean daily AP score ≥2, based on the unweighted CDAI component of AP
4. Active transmural activity in at least one segment (segmental MaRIA ≥ 11)
5. a. Has demonstrated inadequate response/intolerance to conventional therapy
(Appendix 3: Definitions of Inadequate Response to or Intolerance of Corticosteroids
or 6-MP/AZA/MTX and Corticosteroid Dependence) and is naïve to, or exposed to but
never failed, advanced therapies16
OR
b. Has previously demonstrated lack of initial response (ie, primary non‐responders),
responded initially but then lost response with continued therapy (ie, secondary
non-responders), or was intolerant to a maximum of 1 class of advanced therapies at a
dose approved for the treatment of Crohn's disease (ie, JAK inhibitors, infliximab,
adalimumab, certolizumab pegol, vedolizumab, ustekinumab, or approved biosimilars
for these agents). To note, the proportion of participants that have failed to IL12-23
(eg, ustekinumab) will be limited to around 20% of this advanced therapy non-
responders/intolerant group included in the study (see Section 4.1). Please refer to
Appendix 4: Definition of Inadequate Initial Response, Loss of Response, or
Intolerance to TNF Antagonist Therapies (Infliximab, Adalimumab, or Certolizumab
Pegol), Vedolizumab, or Ustekinumab for details. Inadequate response to JAK
inhibitors is based on the clinical judgment of the investigator.
17
6. Adheres to the following requirements for concomitant medication for the treatment of
Crohn's disease. The following medications are permitted if doses meeting the
requirements listed below are stable or have been discontinued prior to baseline and
within the timeframes specified below:
a. Oral corticosteroids at a prednisone‐equivalent dose at or below 20 mg/day, or
6 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate, and on stable
dosing for at least 2 weeks or if recently discontinued, must have been stopped for at
least 2 weeks.
b. If the participant was on 5-ASA therapy at baseline, they must have been on a stable
dose for at least 2 weeks, or if recently discontinued, they must have stopped at least 2
weeks before baseline. Participants may continue the 5-ASA treatment if ongoing at
baseline.
c. Conventional immunomodulators (ie, AZA, 6‐MP, or MTX) for at least 12 weeks and
have been on a stable dose for at least 4 weeks or if recently discontinued, must have
been stopped for at least 4 weeks.
d. If receiving antibiotics as a primary treatment of luminal Crohn's disease, doses must
be stable for at least 3 weeks or if recently discontinued, must have been stopped for at
least 3 weeks.
e. If receiving enteral nutrition as a primary treatment for Crohn’s disease, must have
been receiving for at least 2 weeks or if recently discontinued, must have been stopped
for at least 2 weeks.
f. Must agree not to receive a Bacille Calmette-Guérin (BCG) vaccination during the
study and for 12 weeks after receiving the last dose of study intervention.
g. Must agree not to receive a live virus or live bacterial vaccination during the study and
for 12 weeks after receiving the last dose of study intervention.
Note: Participant who requires treatment for latent TB must complete the appropriate course of
TB therapy.
7. Screening laboratory test results within the following parameters, and if 1 or more of
the laboratory parameters is out of range, a single retest of laboratory values is
permitted during the approximate 3-week screening period:
a. Hemoglobin ≥8.0 g/dL
b. White blood cells (WBCs) ≥ 3.0 x 103 /μL
c. Neutrophils ≥1.5 x 103 /μL
d. Platelets ≥100 x 103 /μL
e. Serum creatinine ≤1.5 mg/dL.
f. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 using the Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
g. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations
must be ≤2 times the upper limit of normal range for the laboratory conducting the test.
h. Direct (conjugated) bilirubin ≤1.5 x ULN.
Must be otherwise healthy on the basis of clinical laboratory tests performed at screening. If the
results of the serum chemistry panel, including liver enzymes hematology, or urinalysis are
outside the normal reference ranges, the participant may be included only if the investigator
judges the abnormalities or deviations from normal to be not clinically significant or to be
appropriate and reasonable for the population under study. This determination must be recorded
in the participant's source documents and initialed by the investigator.
.
Sex and Contraceptive/Barrier Requirements
8. A female participant of childbearing potential all female participants must have a
negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) at
screening.
9. A female participant must be (as defined in Appendix 8: Contraceptive and Barrier
Guidance)
a. Not of childbearing potential
OR
b. Of childbearing potential and practicing a highly effective method of contraception
(failure rate of ＜1% per year when used consistently and correctly) and agrees to remain
on a highly effective method while receiving study intervention and until 150 days after
last dose - the end of relevant systemic exposure. The investigator must evaluate the
potential for contraceptive method failure (eg, noncompliance, recently initiated) in
relationship to the first dose of study intervention. Examples of highly effective
methods of contraception are located in Appendix 8: Contraceptive and Barrier
Guidance.
Note: If a participant’s childbearing potential changes after start of the study (eg, a
premenarchal woman experiences menarche) or the risk of pregnancy changes (eg, a
woman who is not heterosexually active becomes active), a woman must begin using a
highly effective method of contraception,
18
as described throughout the inclusion and
exclusion criteria.
10. A male participant must wear a condom when engaging in any activity that allows for
passage of ejaculate to another person for 90 days after the last dose of azathioprine
guselkumab or placebo. Male participants must also be advised of the benefit for a
female partner to use a highly effective method of contraception as condom may break
or leak.
11. Woman of childbearing potential or man capable of fathering children must be using
adequate birth control measures. Donation of Ova, oocytes and sperm for the purpose
of assisted reproduction during the study and for a period of 12 weeks after the last
administration of study interventions are prohibited.
Informed Consent
12. Must sign an informed consent form (ICF) (or their legally acceptable representative
when permitted by local regulations must sign) indicating that he/she understands the
purpose of, and procedures required for, the study and is willing to participate.
13. Be willing and able to adhere to all specified requirements including but not limited to
completion of assessments, adherence to visit schedule etc, as specified in this protocol.

臨床試驗計畫

一項第3b 期、開放性、多中心試驗，評估Guselkumab 使用於克隆氏症患者的透壁癒合和疾病

試驗主持人及試驗醫院

適應症