Study Stopped
The Sponsor decided to terminate the study early due to lack of efficacy. There were no safety concerns related to the study.
A Study to Evaluate the Safety and Efficacy of AZD5718 in Participants With Proteinuric Chronic Kidney Disease
A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Multi-Centre, Dose-Ranging Study of AZD5718 in Participants With Proteinuric Chronic Kidney Disease
2 other identifiers
interventional
613
11 countries
111
Brief Summary
The purpose of the study is to evaluate the dose-response efficacy, safety, and pharmacokinetics (PK) of AZD5718 in participants with proteinuric chronic kidney disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2020
111 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 28, 2020
CompletedFirst Posted
Study publicly available on registry
July 30, 2020
CompletedStudy Start
First participant enrolled
October 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 6, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 6, 2022
CompletedResults Posted
Study results publicly available
December 26, 2023
CompletedDecember 20, 2024
November 1, 2024
1.9 years
July 28, 2020
September 5, 2023
November 27, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Reduction of Urine Albumin to Creatinine Ratio (ACR) to Week 20
The dose response effect of AZD5718 on urine ACR at 20 weeks was evaluated. Values less than 1 indicate improvement from baseline.
Week 1 (Baseline) to Week 20
Secondary Outcomes (5)
Change From Baseline in Reduction of Urine ACR to Week 12
Week 1 (Baseline) to Week 12
Number of Participants With Adverse Events and Serious Adverse Events
From Screening (Week -4 to 0) to Week 24
Change From Baseline in 24-hours Mean Systolic Blood Pressure to Week 12
Week 1 (Baseline) to Week 12
Plasma Concentrations of AZD5718
From Week 2 to Week 20
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
Week 1 (Baseline), Week 2, Week 4, Week 8, and Week 12
Study Arms (4)
AZD5718 Dose 1 + Dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose 1 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
AZD5718 Dose 2 + Dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose 2 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
AZD5718 Dose 3 + Dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose 3 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
Placebo + Dapagliflozin 10 mg
PLACEBO COMPARATORParticipants will receive once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
Interventions
Participants will receive once daily oral dose of AZD5718 as per the arms they are randomised, and will continue until Week 20.
Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.
Participants will receive once daily oral dose of placebo matched to AZD5718, and will continue until Week 20.
Eligibility Criteria
You may qualify if:
- Capable of giving signed informed consent form.
- Male or female adults, \>= 18 years of age at study entry.
- For participants who haven't reached the age of maturity according to local regulations in their country, a written informed consent should be obtained from the participant and participants legally acceptable representative.
- Body weight within 50-150 kg and body mass index within the range 18 to 45 kg/m\^2.
- Participants with proteinuric CKD defined as:
- eGFR 20 - 75 mL/min/1.73m\^2 based on Chronic Kidney Disease Epidemiology Collaboration equation at Screening Visit 1.
- 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.
- Participants with diagnosis of Type 2 Diabetes Mellitus (DM) \[for DKD sub-group only\].
- Females of non-childbearing potential must have been surgically sterilized or be postmenopausal, and all female participants must have a negative pregnancy test at screening and prior to study drug administration.
- Male participants must be surgically sterile or agree to use highly effective contraceptives. Non-sterilized 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. Approved/Certified measurements in Japan are as Vasectomy, tubal occlusion, intrauterine device (provided coils are copper banded), levonorgestrel intrauterine system (eg, Mirena®). These measurements are acceptable forms of highly effective birth control in Japan. Not Approved/Certified measurements in Japan are as: Cerazette® (desogestrel) pills, 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®).
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional exploratory genetic research.
- Participants should have: a) stable blood pressure (BP \[BP \<= 150/100 mmHg at Visit 1, and 3\]); b)stable dose of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) for at least 4 weeks prior to Screening Visit 1; c) participants who have been unable to tolerate ACEi or ARB therapy may be enrolled.
- Participants must have been on a stable dose for at least 4 weeks prior to Screening Visit 1, who have been on additional antihypertensives (including diuretics); on treatment with drugs with potential to influence albuminuria eg., non-steroidal anti-inflammatory drug; on renin inhibitor or an aldosterone antagonist in combination with an ACEi or an ARB.
- Participants on Sodium-glucose co-transporter-2 inhibitors (SGLT2i) or Glucagon-like peptide-1 receptor agonist (GLP1-RA) treatment, the participants must have been on a stable dose for at least 4 weeks prior to randomization visit.
You may not qualify if:
- Participants with recent positive hepatitis B or hepatitis C.
- Diagnosis of polycystic kidney disease or anatomical causes of CKD.
- Diagnosis of Type 1 DM.
- Participants with severe hepatic impairment (Child-Pugh class C).
- Abnormal laboratory findings at Screening Visit 1.
- Any of the following concomitant conditions or diseases at Screening Visit 1:
- History of QT prolongation associated with other medications that required discontinuation of that medication, and congenital long QT syndrome.
- Acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass grafting within 6 months.
- High degree atrioventricular block II-III, sinus node dysfunction.
- Stroke within 3 months, heart failure, and anticipated dialysis or renal transplantation within 1 year.
- Any other condition or clinically relevant abnormal findings in physical examination, laboratory results or ECG during screening period.
- History of substance dependence or a positive screen for drugs or alcohol abuse. Alcohol and drug screening to be completed for all participants locally with laboratory kits provided by the central laboratory.
- 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.
- Ongoing use of any biologic drug and/or small molecule targeting the immune system.
- Any serum creatinine-altering drugs within 1 month prior to Screening Visit 1.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Parexelcollaborator
- Emerald Clinical Inc.collaborator
Study Sites (111)
Research Site
Canoga Park, California, 91303, United States
Research Site
La Mesa, California, 91942, United States
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San Carlos, California, 94070, United States
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San Francisco, California, 94110, United States
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Victorville, California, 92392, United States
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Denver, Colorado, 80045, United States
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Jacksonville, Florida, 32216, United States
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Winter Haven, Florida, 33880, United States
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Columbus, Georgia, 31904, United States
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Roseville, Michigan, 48066, United States
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Hazelwood, Missouri, 63042, United States
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Fresh Meadows, New York, 11365, United States
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Great Neck, New York, 11021, United States
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Jamaica, New York, 11432, United States
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Blue Ash, Ohio, 45242, United States
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East Providence, Rhode Island, 02914, United States
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Memphis, Tennessee, 38104-2127, United States
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Austin, Texas, 78738, United States
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Houston, Texas, 77099, United States
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Pearland, Texas, 77584, United States
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San Antonio, Texas, 78215, United States
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Schertz, Texas, 78154, United States
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Bahía Blanca, B8109, Argentina
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Buenos Aires, 1280, Argentina
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Córdoba, 5000, Argentina
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Córdoba, X5016KEH, Argentina
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Córdoba, X5016KET, Argentina
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Junín, 6000, Argentina
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Mar del Plata, B7600, Argentina
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Belém, 66073-005, Brazil
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Brasília, 71625-175, Brazil
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Curitiba, 80215-901, Brazil
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Fortaleza, 60430-375, Brazil
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Meireles, 60160-230, Brazil
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Porto Alegre, 90035-074, Brazil
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Porto Alegre, 90430-001, Brazil
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Santo André, 09090-790, Brazil
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São Paulo, 01323-020, Brazil
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São Paulo, 05016-090, Brazil
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São Paulo, 05403-9000, Brazil
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Aschaffenburg, 63739, Germany
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Berlin, 13509, Germany
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Essen, 45136, Germany
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Trier, 54292, Germany
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Balatonfüred, 8230, Hungary
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Budapest, 1083, Hungary
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Budapest, 1115, Hungary
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Debrecen, 4032, Hungary
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Szentes, 6600, Hungary
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Szigetvár, 7900, Hungary
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Afula, 1834111, Israel
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Ashdod, 7747629, Israel
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Ashkelon, 78306, Israel
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Haifa, 34362, Israel
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Jerusalem, 91031, Israel
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Ageo, 362-8588, Japan
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Asahikawa-shi, 070-8530, Japan
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Chiba, 261-0004, Japan
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Hiroshima, 732-0057, Japan
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Kasugai-shi, 486-8510, Japan
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Kitakyushu, 805-8508, Japan
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Koga-shi, 306-0041, Japan
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Kyoto, 604-8845, Japan
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Mito, 311-4198, Japan
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Morioka, 020-0066, Japan
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Osaka, 530-0005, Japan
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Osaka, 553-0003, Japan
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Osaka, 558-8558, Japan
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Sashima-gun, 306-0433, Japan
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Shizuoka, 420-8630, Japan
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Toride-shi, 302-0022, Japan
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Yokohama, 234-0054, Japan
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Yokohama, 236-0004, Japan
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Yokohama, 247-8581, Japan
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Kota Kinabalu, 88586, Malaysia
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Kuala Lumpur, 50586, Malaysia
Research Site
Kuala Lumpur, 56000, Malaysia
Research Site
Kuala Lumpur, 59100, Malaysia
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Malacca, 78300, Malaysia
Research Site
Seremban, 70300, Malaysia
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Seri Manjung, 32040, Malaysia
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Sibu, 96000, Malaysia
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Bialystok, 15-375, Poland
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Bialystok, 15-435, Poland
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Krakow, 31-559, Poland
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Lodz, 92-213, Poland
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Oświęcim, 32-600, Poland
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Rzeszów, 35-055, Poland
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Kaohsiung City, 82445, Taiwan
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Kaohsiung City, 833, Taiwan
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Keelung, 20448, Taiwan
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New Taipei City, 23148, Taiwan
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Taichung, 40443, Taiwan
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Taichung, 40705, Taiwan
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Taichung, 433, Taiwan
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Taipei, 100, Taiwan
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Taipei, 116, Taiwan
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Taipei, Taiwan
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Dnipro, 49005, Ukraine
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Dnipro, 49038, Ukraine
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Ivano-Frankivsk, 76000, Ukraine
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Ivano-Frankivsk, 76014, Ukraine
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Kyiv, 02125, Ukraine
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Kyiv, 03049, Ukraine
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Kyiv, 1004, Ukraine
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Lviv, 79010, Ukraine
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Uzhhorod, 88018, Ukraine
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Vinnytsia, 21001, Ukraine
Research Site
Vinnytsia, 21010, Ukraine
Research Site
Zaporizhzhia, 69600, Ukraine
Research Site
Zhytomyr, 10002, Ukraine
Related Publications (1)
Heerspink HJL, Law G, Psachoulia K, Connolly K, Whatling C, Ericsson H, Knochel J, Lindstedt EL, MacPhee I. Design of FLAIR: a Phase 2b Study of the 5-Lipoxygenase Activating Protein Inhibitor AZD5718 in Patients With Proteinuric CKD. Kidney Int Rep. 2021 Aug 27;6(11):2803-2810. doi: 10.1016/j.ekir.2021.08.018. eCollection 2021 Nov.
PMID: 34805632DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Following study termination and reduced scope of the analysis, the PK analysis has not been performed.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Hiddo J. L. Heerspink
Department of Clinical Pharmacy and Pharmacology University Medical Centre Groningen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- No member of the study team at AstraZeneca, or representative, personnel at study centres, or any CRO handling data will have access to the randomization scheme prior to unblinding for the primary analysis.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 28, 2020
First Posted
July 30, 2020
Study Start
October 1, 2020
Primary Completion
September 6, 2022
Study Completion
September 6, 2022
Last Updated
December 20, 2024
Results First Posted
December 26, 2023
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.