計劃書編號D7551C00001
2021-01-22 - 2023-03-23
Phase II
尚未開始2
召募中8
一項針對患有蛋白尿型慢性腎臟病參與者的第 2b期隨機分配、雙盲、安慰劑對照、多中心 的 AZD5718劑量範圍試驗
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試驗申請者
百瑞精鼎國際股份有限公司
-
試驗委託 / 贊助單位名稱
AstraZeneca AB
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臨床試驗規模
多國多中心
-
更新日期
2025/08/20
試驗主持人及試驗醫院
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
適應症
蛋白尿型慢性腎臟病
試驗目的
主要目的
• 評估蛋白尿型CKD參與者在20週時AZD5718對尿液肌酸酐比值(ACR)的劑量反應效應(在第12至20週以dapagliflozin治療作為未來的照護標準)
次要目的
• 評估AZD5718在12週時對尿液ACR的劑量反應療效(依目前照護標準)
• 在蛋白尿型CKD參與者中評估AZD5718的安全性及耐受性
• 評估AZD5718對蛋白尿型CKD參與者動態血壓的影響
• 評估患有蛋白尿型CKD的參與者重複口服給藥AZD5718 20週後之PK
• 評估AZD5718對蛋白尿型CKD參與者，增加與不增加dapagliflozin於腎功能的效果
探索性
• 評估AZD5718對蛋白尿型CKD參與者5-LO途徑活性生物標記的劑量反應效應
• 評估蛋白尿型CKD參與者對AZD5718治療反應和/或可以預測對AZD5718治療反應的探索性生物標記
• 評估AZD5718對蛋白尿型CKD參與者的DKD次組中，糖尿病性視網膜病變的效果
• 評估患有蛋白尿型CKD的參與者重複口服給藥dapagliflozin 8週後之PK
藥品名稱
AZD5718 tablets
主成份
AZD5718
劑型
錠劑
劑量
10mg, 25mg, 125mg
評估指標
評估AZD5718在12週時對尿液ACR的劑量反應療效(依目前照護標準)
在蛋白尿型CKD參與者中評估AZD5718的安全性及耐受性
評估AZD5718對蛋白尿型CKD參與者動態血壓的影響
評估患有蛋白尿型CKD的參與者重複口服給藥AZD5718 20週後之PK
評估AZD5718對蛋白尿型CKD參與者，增加與不增加dapagliflozin於腎功能的效果
在蛋白尿型CKD參與者中評估AZD5718的安全性及耐受性
評估AZD5718對蛋白尿型CKD參與者動態血壓的影響
評估患有蛋白尿型CKD的參與者重複口服給藥AZD5718 20週後之PK
評估AZD5718對蛋白尿型CKD參與者，增加與不增加dapagliflozin於腎功能的效果
主要納入條件
Inclusion Criteria
Age
1 Participants must be ≥ 18 years of age inclusive, at the time of signing the informed
consent.
For participants aged 18 to ＜ 20 years and enrolled in Japan, a written informed consent
should be obtained from the participant and his or her legally acceptable representative.
Type of Participant and Disease Characteristics
2 Participants with proteinuric CKD defined as
eGFR 20 – 75 mL/min/1.73m2 based on CKD-EPI equation at Visit 1 and
albuminuria defined as 200 -5000 mg albumin/g creatinine based on the geometric
mean of the replicated measurements using 3 sequential first morning void urine at
Visit 2.
and
with diagnosis of T2DM (for DKD sub-group only).
Weight
3 Body weight within 50-150 kg and BMI within the range 18 to 45 kg/m2 (inclusive).
Sex
4 Male or female
5 Female participants must be of non-childbearing potential and must have been surgically
sterilised (ie, bilateral oophorectomy, complete hysterectomy, or bilateral tube ligation),
or be postmenopausal (assessed by serum FSH and LH levels at Screening Visit 1). All
female participants must have a negative serum pregnancy test at Screening Visit 1 and
negative urine pregnancy test at Visit 3 (Day 1) prior to study drug administration.
6 Male participants must be surgically sterile or agree to use highly effective
contraceptives. Non-sterilised male participants who are sexually active with a female
partner of childbearing potential must use a male condom with spermicide from Day 1 to
3 months after the last dose of the study drug. It is strongly recommended for the female
partner of a male participant to also use a highly effective method of contraception
throughout this period.
Note: In case a male condom with spermicide is not available in a country or region,
non-sterilised male participants who are sexually active with a female partner of
childbearing potential must use a male condom without spermicide and the female partner
should use a highly effective contraceptive method.
Note: Highly effective birth control methods for female partners of male participants
include: total sexual abstinence (true abstinence in line with the preferred and usual
lifestyle choice of the participant), vasectomised partner, tubal occlusion, intrauterine
device (provided coils are copper banded), levonorgestrel intrauterine system (eg,
Mirena®), medroxyprogesterone injections (eg, Depo-Provera®), etonogestrel implants (eg, Implanon®, Norplan®), normal and low dose combined oral pills,
norelgestromin/ethinylestradiol transdermal system (eg Evra® Patch), Intravaginal device
(eg, NuvaRing®), and Cerazette® (desogestrel) pills.
Informed Consent
7 Capable of giving signed informed consent as described in Appendix A which includes
compliance with the requirements and restrictions listed in the ICF and in this CSP.
8 Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples for optional exploratory genetic research that
supports Genomic Initiative.
Other Criteria
9 Participants should have a stable BP meeting all of the following criteria:
(a) BP ≤ 150/100 mmHg at Visit 1 and Visit 3.
(b) Stable dose of ACEi or ARB for at least 4 weeks prior to Visit 1 with ACEi and ARB
dosing according to local guidelines. Participants who have been deemed unable to
tolerate ACEi or ARB therapy due to allergy or complications may be enrolled.
10 For participants on any additional antihypertensive medication (including diuretic
therapy), the doses must be stable for at least 4 weeks prior to Visit 1.
11 If on SGLT2i or GLP1-RA treatment, the participants must have been on a stable dose for
at least 4 weeks prior to randomisation visit. No new additional SGLT2i or GLP1-RA
therapy is permitted until the 8-week extension period.
12 If on treatment with other drugs with potential to influence albuminuria, eg NSAIDs, the
participants must have been on a stable dose for at least 4 weeks prior to Screening
Visit 1.
13 Renin inhibitor or an aldosterone antagonist in combination with an ACEi or an ARB
(dual renin angiotensin aldosterone system inhibitor therapy) is permitted and participants
must have been on a stable dose for at least 4 weeks prior to Screening Visit 1.
Exclusion Criteria
Medical Conditions
1 Recent hepatitis, or positive screening test for hepatitis B (hepatitis B virus surface
antigen) or hepatitis C (hepatitis C antibody).
2 Diagnosis of polycystic kidney disease or anatomical causes of CKD.
3 Diagnosis of T1DM.
4 Participants with severe hepatic impairment (Child-Pugh class C).
5 Abnormal laboratory findings at Screening Visit 1
(a) Alanine aminotransferase or AST ＞ 2 × ULN or total bilirubin ＞ 2 × ULN (unless
due to Gilbert’s disease) or evidence of chronic liver disease.
(b) Serum potassium ＞ 5.5 mmol/L that cannot be adjusted to values ≤ 5.5 mmol/L by
appropriate management.
6 Any of the following concomitant conditions or diseases at Screening Visit 1
(a) History of QT prolongation associated with other medications that required
discontinuation of that medication.
(b) Congenital long QT syndrome.
(c) Acute coronary syndrome, percutaneous coronary intervention, coronary artery
bypass grafting within 6 months.
(d) High degree atrioventricular block II-III, sinus node dysfunction with significant
sinus pause, untreated with pacemaker.
(e) Stroke within 3 months.
(f) Heart failure New York Heart Association classification III-IV.
(g) Anticipated dialysis or renal transplantation within 1 year.
(h) History of substance dependence or a positive screen for drugs or alcohol abuse,
likely to impact participant safety or compliance with study procedures, at the
discretion of the Investigator. Alcohol and drug screening to be completed for all
participants locally with laboratory kits provided by the central laboratory.
(i) Prior malignancy other than non-melanoma skin cancer or cervical cancer in situ
treated with apparent success with curative therapy (response duration of ＞ 5 years).
(j) Any other condition or clinically relevant abnormal findings in physical examination,
laboratory results or ECG during screening period that, in the opinion of the
Investigator, may compromise the safety of the participant in the study, reduce the
participant’s ability to participate in the study, or interfere with evaluation of the
study drug.
7 Participant who had severe course of COVID-19 (extracorporeal membrane oxygenation,
mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks of
Screening Visit 1 (for further details See Appendix F).
Prior/Concomitant Therapy
8 Ongoing use of any biologic drug and/or small molecule targeting the immune system
(for example, tumour necrosis factor blockers, anakinra, rituximab, abatacept,
azathioprine, mycophenolate, cyclophosphamide, tocilizumab, corticosteroids other than
topical or inhaled).
9 Any serum creatinine-altering drugs within 1 month prior to Screening Visit 1 including
but not limited to amphotericin, cimetidine, clofibrate, dronedarone, ketoconazole,
probenecid, ranolazine, trimethoprim, aminoglycosides, or cephalosporins.
10 Any concomitant medications known to be associated with Torsades de Pointes or potent
inducers/inhibitors of cytochrome P450 3A4.
11 Treatment with zileuton, cilastatin (DPEP1 inhibitor), or leukotriene receptor antagonists
(eg, montelukast) within 4 weeks of Screening Visit 1.
12 Treatment with simvastatin, lovastatin, and atorvastatin at doses ＞ 40 mg per day within
1 month prior to Screening Visit 1.
Prior/Concurrent Clinical Study Experience
13 Concurrent enrolment in another clinical study involving an investigational treatment or
drug or participation in a device study within 3 months prior to Screening Visit 1.
14 Participants with a known hypersensitivity to AZD5718 or any of the excipients of the
product.
Other Exclusions
15 Donation of blood or significant blood loss in excess of 500 mL within 3 months prior to
Day 1 (or ＞ 1200 mL in the year prior to Day 1).
16 Plasma donation within 60 days prior to Day 1.
17 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study centre).
18 Judgement by the Investigator that the participant should not participate in the study if the
participant is unlikely to comply with study procedures, restrictions, and requirements.
19 For women only - currently pregnant (a negative serum pregnancy test is required at
Screening Visit 1 and urine pregnancy test at Day 1 [Visit 3]) or breast-feeding.
20 An employee, or close relative of an employee, of AstraZeneca, the CRO, or the study
site, regardless of the employee’s role.
21 Participants who are legally institutionalised.N/A
Age
1 Participants must be ≥ 18 years of age inclusive, at the time of signing the informed
consent.
For participants aged 18 to ＜ 20 years and enrolled in Japan, a written informed consent
should be obtained from the participant and his or her legally acceptable representative.
Type of Participant and Disease Characteristics
2 Participants with proteinuric CKD defined as
eGFR 20 – 75 mL/min/1.73m2 based on CKD-EPI equation at Visit 1 and
albuminuria defined as 200 -5000 mg albumin/g creatinine based on the geometric
mean of the replicated measurements using 3 sequential first morning void urine at
Visit 2.
and
with diagnosis of T2DM (for DKD sub-group only).
Weight
3 Body weight within 50-150 kg and BMI within the range 18 to 45 kg/m2 (inclusive).
Sex
4 Male or female
5 Female participants must be of non-childbearing potential and must have been surgically
sterilised (ie, bilateral oophorectomy, complete hysterectomy, or bilateral tube ligation),
or be postmenopausal (assessed by serum FSH and LH levels at Screening Visit 1). All
female participants must have a negative serum pregnancy test at Screening Visit 1 and
negative urine pregnancy test at Visit 3 (Day 1) prior to study drug administration.
6 Male participants must be surgically sterile or agree to use highly effective
contraceptives. Non-sterilised male participants who are sexually active with a female
partner of childbearing potential must use a male condom with spermicide from Day 1 to
3 months after the last dose of the study drug. It is strongly recommended for the female
partner of a male participant to also use a highly effective method of contraception
throughout this period.
Note: In case a male condom with spermicide is not available in a country or region,
non-sterilised male participants who are sexually active with a female partner of
childbearing potential must use a male condom without spermicide and the female partner
should use a highly effective contraceptive method.
Note: Highly effective birth control methods for female partners of male participants
include: total sexual abstinence (true abstinence in line with the preferred and usual
lifestyle choice of the participant), vasectomised partner, tubal occlusion, intrauterine
device (provided coils are copper banded), levonorgestrel intrauterine system (eg,
Mirena®), medroxyprogesterone injections (eg, Depo-Provera®), etonogestrel implants (eg, Implanon®, Norplan®), normal and low dose combined oral pills,
norelgestromin/ethinylestradiol transdermal system (eg Evra® Patch), Intravaginal device
(eg, NuvaRing®), and Cerazette® (desogestrel) pills.
Informed Consent
7 Capable of giving signed informed consent as described in Appendix A which includes
compliance with the requirements and restrictions listed in the ICF and in this CSP.
8 Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples for optional exploratory genetic research that
supports Genomic Initiative.
Other Criteria
9 Participants should have a stable BP meeting all of the following criteria:
(a) BP ≤ 150/100 mmHg at Visit 1 and Visit 3.
(b) Stable dose of ACEi or ARB for at least 4 weeks prior to Visit 1 with ACEi and ARB
dosing according to local guidelines. Participants who have been deemed unable to
tolerate ACEi or ARB therapy due to allergy or complications may be enrolled.
10 For participants on any additional antihypertensive medication (including diuretic
therapy), the doses must be stable for at least 4 weeks prior to Visit 1.
11 If on SGLT2i or GLP1-RA treatment, the participants must have been on a stable dose for
at least 4 weeks prior to randomisation visit. No new additional SGLT2i or GLP1-RA
therapy is permitted until the 8-week extension period.
12 If on treatment with other drugs with potential to influence albuminuria, eg NSAIDs, the
participants must have been on a stable dose for at least 4 weeks prior to Screening
Visit 1.
13 Renin inhibitor or an aldosterone antagonist in combination with an ACEi or an ARB
(dual renin angiotensin aldosterone system inhibitor therapy) is permitted and participants
must have been on a stable dose for at least 4 weeks prior to Screening Visit 1.
Exclusion Criteria
Medical Conditions
1 Recent hepatitis, or positive screening test for hepatitis B (hepatitis B virus surface
antigen) or hepatitis C (hepatitis C antibody).
2 Diagnosis of polycystic kidney disease or anatomical causes of CKD.
3 Diagnosis of T1DM.
4 Participants with severe hepatic impairment (Child-Pugh class C).
5 Abnormal laboratory findings at Screening Visit 1
(a) Alanine aminotransferase or AST ＞ 2 × ULN or total bilirubin ＞ 2 × ULN (unless
due to Gilbert’s disease) or evidence of chronic liver disease.
(b) Serum potassium ＞ 5.5 mmol/L that cannot be adjusted to values ≤ 5.5 mmol/L by
appropriate management.
6 Any of the following concomitant conditions or diseases at Screening Visit 1
(a) History of QT prolongation associated with other medications that required
discontinuation of that medication.
(b) Congenital long QT syndrome.
(c) Acute coronary syndrome, percutaneous coronary intervention, coronary artery
bypass grafting within 6 months.
(d) High degree atrioventricular block II-III, sinus node dysfunction with significant
sinus pause, untreated with pacemaker.
(e) Stroke within 3 months.
(f) Heart failure New York Heart Association classification III-IV.
(g) Anticipated dialysis or renal transplantation within 1 year.
(h) History of substance dependence or a positive screen for drugs or alcohol abuse,
likely to impact participant safety or compliance with study procedures, at the
discretion of the Investigator. Alcohol and drug screening to be completed for all
participants locally with laboratory kits provided by the central laboratory.
(i) Prior malignancy other than non-melanoma skin cancer or cervical cancer in situ
treated with apparent success with curative therapy (response duration of ＞ 5 years).
(j) Any other condition or clinically relevant abnormal findings in physical examination,
laboratory results or ECG during screening period that, in the opinion of the
Investigator, may compromise the safety of the participant in the study, reduce the
participant’s ability to participate in the study, or interfere with evaluation of the
study drug.
7 Participant who had severe course of COVID-19 (extracorporeal membrane oxygenation,
mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks of
Screening Visit 1 (for further details See Appendix F).
Prior/Concomitant Therapy
8 Ongoing use of any biologic drug and/or small molecule targeting the immune system
(for example, tumour necrosis factor blockers, anakinra, rituximab, abatacept,
azathioprine, mycophenolate, cyclophosphamide, tocilizumab, corticosteroids other than
topical or inhaled).
9 Any serum creatinine-altering drugs within 1 month prior to Screening Visit 1 including
but not limited to amphotericin, cimetidine, clofibrate, dronedarone, ketoconazole,
probenecid, ranolazine, trimethoprim, aminoglycosides, or cephalosporins.
10 Any concomitant medications known to be associated with Torsades de Pointes or potent
inducers/inhibitors of cytochrome P450 3A4.
11 Treatment with zileuton, cilastatin (DPEP1 inhibitor), or leukotriene receptor antagonists
(eg, montelukast) within 4 weeks of Screening Visit 1.
12 Treatment with simvastatin, lovastatin, and atorvastatin at doses ＞ 40 mg per day within
1 month prior to Screening Visit 1.
Prior/Concurrent Clinical Study Experience
13 Concurrent enrolment in another clinical study involving an investigational treatment or
drug or participation in a device study within 3 months prior to Screening Visit 1.
14 Participants with a known hypersensitivity to AZD5718 or any of the excipients of the
product.
Other Exclusions
15 Donation of blood or significant blood loss in excess of 500 mL within 3 months prior to
Day 1 (or ＞ 1200 mL in the year prior to Day 1).
16 Plasma donation within 60 days prior to Day 1.
17 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study centre).
18 Judgement by the Investigator that the participant should not participate in the study if the
participant is unlikely to comply with study procedures, restrictions, and requirements.
19 For women only - currently pregnant (a negative serum pregnancy test is required at
Screening Visit 1 and urine pregnancy test at Day 1 [Visit 3]) or breast-feeding.
20 An employee, or close relative of an employee, of AstraZeneca, the CRO, or the study
site, regardless of the employee’s role.
21 Participants who are legally institutionalised.N/A
試驗計畫預計收納受試者人數
-
台灣人數
60 人
-
全球人數
632 人
