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Chronic Kidney DiseasePhase 2NCT04492722

A Study to Evaluate the Safety and Efficacy of AZD5718 in Participants With Proteinuric Chronic Kidney Disease

A Phase 2 study testing AZD5718 and Dapagliflozin 10 mg in people with Chronic Kidney Disease, run by AstraZeneca at 111 sites in 11 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Chronic Kidney Disease
What is being tested?
AZD5718 and Dapagliflozin 10 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
613 participants
Where
111 sitesin 11 countries
Study dates
1 Oct 2020to 6 Sep 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 14Show fewer
  • 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.

Who cannot join

  • 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:
Show all 28Show fewer
  • 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.
  • Treatment with any concomitant medications known to be associated with Torsades de Pointes or potent inducers/inhibitors of cytochrome P450 3A4 within 4 weeks of Visit 3 (Randomization).
  • Treatment with zileuton, cilastatin (dipeptidase-1 [DPEP1] inhibitor), or leukotriene receptor antagonists (eg, montelukast) within 4 weeks of Screening Visit 1.
  • Treatment with simvastatin, lovastatin, and atorvastatin at doses > 40 mg per day within 1 month prior to Screening Visit 1.
  • Concurrent enrollment in another clinical study involving an investigational treatment or drug or participation in a device study within 3 months prior to Screening Visit 1.
  • Participants with a known hypersensitivity to AZD5718 or any of the excipients of the product. Participants with a known hypersensitivity to dapagliflozin or any of the excipients of the product.
  • 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).
  • Plasma donation within 60 days prior to Day 1.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study center).
  • 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.
  • 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.
  • An employee, or close relative of an employee, of AstraZeneca, the Contract Research Organisation, or the study site, regardless of the employee's role.
  • Participants who are legally institutionalized.
  • Participants working night shifts, and who cannot avoid strenuous manual labour during the study.

Trial locations and contacts

111 sites in 11 countries.

111 sites in 11 countries

United States22 sites

  • Research Site

    Austin, Texas, 78738

  • Research Site

    Blue Ash, Ohio, 45242

  • Research Site

    Canoga Park, California, 91303

  • Research Site

    Columbus, Georgia, 31904

  • Research Site

    Denver, Colorado, 80045

  • Research Site

    East Providence, Rhode Island, 02914

  • Research Site

    Fresh Meadows, New York, 11365

  • Research Site

    Great Neck, New York, 11021

  • Research Site

    Hazelwood, Missouri, 63042

  • Research Site

    Houston, Texas, 77099

  • Research Site

    Jacksonville, Florida, 32216

  • Research Site

    Jamaica, New York, 11432

  • Research Site

    La Mesa, California, 91942

  • Research Site

    Memphis, Tennessee, 38104-2127

  • Research Site

    Pearland, Texas, 77584

  • Research Site

    Roseville, Michigan, 48066

  • Research Site

    San Antonio, Texas, 78215

  • Research Site

    San Carlos, California, 94070

  • Research Site

    San Francisco, California, 94110

  • Research Site

    Schertz, Texas, 78154

  • Research Site

    Victorville, California, 92392

  • Research Site

    Winter Haven, Florida, 33880

Other trials in United States

Japan19 sites

  • Research Site

    Ageo, 362-8588

  • Research Site

    Asahikawa-shi, 070-8530

  • Research Site

    Chiba, 261-0004

  • Research Site

    Hiroshima, 732-0057

  • Research Site

    Kasugai-shi, 486-8510

  • Research Site

    Kitakyushu, 805-8508

  • Research Site

    Koga-shi, 306-0041

  • Research Site

    Kyoto, 604-8845

  • Research Site

    Mito, 311-4198

  • Research Site

    Morioka, 020-0066

  • Research Site

    Osaka, 530-0005

  • Research Site

    Osaka, 553-0003

  • Research Site

    Osaka, 558-8558

  • Research Site

    Sashima-gun, 306-0433

  • Research Site

    Shizuoka, 420-8630

  • Research Site

    Toride-shi, 302-0022

  • Research Site

    Yokohama, 234-0054

  • Research Site

    Yokohama, 236-0004

  • Research Site

    Yokohama, 247-8581

Other trials in Japan

Ukraine13 sites

  • Research Site

    Dnipro, 49005

  • Research Site

    Dnipro, 49038

  • Research Site

    Ivano-Frankivsk, 76000

  • Research Site

    Ivano-Frankivsk, 76014

  • Research Site

    Kyiv, 02125

  • Research Site

    Kyiv, 03049

  • Research Site

    Kyiv, 1004

  • Research Site

    Lviv, 79010

  • Research Site

    Uzhhorod, 88018

  • Research Site

    Vinnytsia, 21001

  • Research Site

    Vinnytsia, 21010

  • Research Site

    Zaporizhzhya, 69600

  • Research Site

    Zhytomyr, 10002

Other trials in Ukraine

Brazil11 sites

  • Research Site

    Belém, 66073-005

  • Research Site

    Brasília, 71625-175

  • Research Site

    Curitiba, 80215-901

  • Research Site

    Fortaleza, 60430-375

  • Research Site

    Meireles, 60160-230

  • Research Site

    Porto Alegre, 90035-074

  • Research Site

    Porto Alegre, 90430-001

  • Research Site

    Santo André, 09090-790

  • Research Site

    São Paulo, 01323-020

  • Research Site

    São Paulo, 05016-090

  • Research Site

    São Paulo, 05403-9000

Other trials in Brazil

Taiwan10 sites

  • Research Site

    Kaohsiung City, 82445

  • Research Site

    Kaohsiung City, 833

  • Research Site

    Keelung, 20448

  • Research Site

    New Taipei City, 23148

  • Research Site

    Taichung, 40443

  • Research Site

    Taichung, 40705

  • Research Site

    Taichung, 433

  • Research Site

    Taipei, 100

  • Research Site

    Taipei, 116

  • Research Site

    Taipei

Other trials in Taiwan

Malaysia8 sites

  • Research Site

    Kota Kinabalu, 88586

  • Research Site

    Kuala Lumpur, 50586

  • Research Site

    Kuala Lumpur, 56000

  • Research Site

    Kuala Lumpur, 59100

  • Research Site

    Malacca, 78300

  • Research Site

    Seremban, 70300

  • Research Site

    Seri Manjung, 32040

  • Research Site

    Sibu, 96000

Other trials in Malaysia

Argentina7 sites

  • Research Site

    Bahía Blanca, B8109

  • Research Site

    Buenos Aires, 1280

  • Research Site

    Córdoba, 5000

  • Research Site

    Córdoba, X5016KEH

  • Research Site

    Córdoba, X5016KET

  • Research Site

    Junín, 6000

  • Research Site

    Mar del Plata, B7600

Other trials in Argentina

Hungary6 sites

  • Research Site

    Balatonfüred, 8230

  • Research Site

    Budapest, 1083

  • Research Site

    Budapest, 1115

  • Research Site

    Debrecen, 4032

  • Research Site

    Szentes, 6600

  • Research Site

    Szigetvár, 7900

Other trials in Hungary

Poland6 sites

  • Research Site

    Bialystok, 15-375

  • Research Site

    Bialystok, 15-435

  • Research Site

    Krakow, 31-559

  • Research Site

    Lodz, 92-213

  • Research Site

    Oświęcim, 32-600

  • Research Site

    Rzeszów, 35-055

Other trials in Poland

Israel5 sites

  • Research Site

    Afula, 1834111

  • Research Site

    Ashdod, 7747629

  • Research Site

    Ashkelon, 78306

  • Research Site

    Haifa, 34362

  • Research Site

    Jerusalem, 91031

Other trials in Israel

Germany4 sites

  • Research Site

    Aschaffenburg, 63739

  • Research Site

    Berlin, 13509

  • Research Site

    Essen, 45136

  • Research Site

    Trier, 54292

Other trials in Germany

About this study

Official title: A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Multi-Centre, Dose-Ranging Study of AZD5718 in Participants With Proteinuric Chronic Kidney Disease

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.

Read the detailed description

The study will be conducted in approximately 118 study centers across 12 countries. The overall study period will be around 28 weeks. Approximately 632 participants comprising of 67% diabetic kidney disease (DKD) and 33% non-DKD participants will be enrolled. After a screening period of up to 4 weeks, the participants will be randomised in a 1:1:1:1 ratio to receive one of the doses of AZD5718 and/or placebo for the first 12 weeks (Day 85 [treatment period 1]), with an add-on therapy of 8 weeks of dapagliflozin for all participants from Week 12 to 20 (Day 85 to 141 [treatment period 2]). Only participants still taking their assigned treatment from treatment period 1 will progress to treatment period 2. Any participant with urine albumin to creatinine ratio (ACR) < 30 mg/g at Week 12 will be excluded from treatment period 2. The eligibility check to enter treatment period 2 will be done at Visit 7 (Week 12) using the last available urine ACR result. The final analysis will be done after all participants have completed follow-up period of up to 4 weeks. The expected total study duration, including the Screening Period, for each participant will be at least 28 weeks.

Being tested
AZD5718, Dapagliflozin 10 mg, Placebo
Keywords
Nephrology, Chronic kidney disease, Proteinuria, Diabetic kidney disease, Diabetes mellitus
Medical subject headings
Renal Insufficiency, Chronic, Proteinuria, Diabetic Nephropathies, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD5718Drug

    Participants will receive once daily oral dose of AZD5718 as per the arms they are randomised, and will continue until Week 20.

  • Dapagliflozin 10 mgDrug

    Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.

  • PlaceboDrug

    Participants will receive once daily oral dose of placebo matched to AZD5718, and will continue until Week 20.

Study groups in NCT04492722
Study groupRoleWhat they receive
AZD5718 Dose 1 + Dapagliflozin 10 mgExperimentalParticipants will receive once daily oral dose 1 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
Receives: Drug: AZD5718; Drug: Dapagliflozin 10 mg
AZD5718 Dose 2 + Dapagliflozin 10 mgExperimentalParticipants will receive once daily oral dose 2 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
Receives: Drug: AZD5718; Drug: Dapagliflozin 10 mg
AZD5718 Dose 3 + Dapagliflozin 10 mgExperimentalParticipants will receive once daily oral dose 3 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
Receives: Drug: AZD5718; Drug: Dapagliflozin 10 mg
Placebo + Dapagliflozin 10 mgPlacebo 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.
Receives: Drug: Dapagliflozin 10 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 1 (Baseline) to Week 20

Secondary outcomes (5)

  1. Change From Baseline in Reduction of Urine ACR to Week 12

    The dose response effect of AZD5718 on urine ACR at 12 weeks was evaluated. Values less than 1 indicate improvement from baseline.

    Measured: Week 1 (Baseline) to Week 12

  2. Number of Participants With Adverse Events and Serious Adverse Events

    The safety and tolerability profile of AZD5718 treatment was assessed

    Measured: From Screening (Week -4 to 0) to Week 24

  3. Change From Baseline in 24-hours Mean Systolic Blood Pressure to Week 12

    The effect of AZD5718 on ambulatory blood pressure was assessed

    Measured: Week 1 (Baseline) to Week 12

  4. Plasma Concentrations of AZD5718

    The PK of AZD5718 after repeated oral dosing for 20 weeks was evaluated

    Measured: From Week 2 to Week 20

  5. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12

    The effect of AZD5718 on renal function was evaluated

    Measured: Week 1 (Baseline), Week 2, Week 4, Week 8, and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2020
  2. Study start1 Oct 2020
  3. Primary completion6 Sep 2022
  4. Study completion6 Sep 2022

Why it stopped: The Sponsor decided to terminate the study early due to lack of efficacy. There were no safety concerns related to the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
613 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04492722
Sponsor's protocol ID
D7551C00001
Other IDs
2020-002263-54
Status last verified
Nov 2024
First submitted
28 Jul 2020
Last updated
20 Dec 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 34805632

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD5718 and Dapagliflozin 10 mg in people with Chronic Kidney Disease, run by AstraZeneca at 111 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 111 sites in United States, Japan, Ukraine, Brazil, Taiwan and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Reduction of Urine Albumin to Creatinine Ratio (ACR) to Week 20 (time frame: Week 1 (Baseline) to Week 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04492722, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.

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