A Phase 2b Diabetic Kidney Disease Study

June 15, 2023 updated by: AstraZeneca

A Phase 2b Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of MEDI3506 in Subjects With Diabetic Kidney Disease

A Phase 2b Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of MEDI3506 in Subjects with Diabetic Kidney Disease

Study Overview

Status

Completed

Detailed Description

This is a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy, safety, PK, and immunogenicity of MEDI3506 on top of standard of care, including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and dapagliflozin in adult subjects with diabetic kidney disease, defined as subjects with type 2 diabetes mellitus (T2DM) and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 with a UACR in the range of 100-3000 mg/g, who meet all eligibility criteria. Approximately 565 subjects, among multiple countries will be randomized to MEDI3506 dose 1, 2, 3 or dose 4, or placebo during a treatment period of 24 weeks. All subjects will receive Dapagliflozin daily, as administered orally from Day 85 to Day 168. The primary objective is to evaluate the effect of MEDI3506 on albuminuria in subjects with DKD. Secondary objectives include evaluating safety, PK and the incidence of ADA during the treatment period.

Study Type

Interventional

Enrollment (Actual)

609

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Buenos Aires, Argentina, C1056ABJ
        • Research Site
      • Buenos Aires, Argentina, 1425DES
        • Research Site
      • Buenos Aires, Argentina, C1429BWN
        • Research Site
      • Caba, Argentina, C1425AGC
        • Research Site
      • Caba, Argentina, C1120AAC
        • Research Site
      • Caba, Argentina, C1128AAF
        • Research Site
      • Cordoba, Argentina, X5000AAW
        • Research Site
      • Corrientes, Argentina, W3400AMZ
        • Research Site
      • Mar del Plata, Argentina, 7600
        • Research Site
      • Pergamino, Argentina, B2700LDK
        • Research Site
      • Ramos Mejía, Argentina, B1704ETD
        • Research Site
      • Rosario, Argentina, S2000DNM
        • Research Site
      • San Luis, Argentina, D5700CTA
        • Research Site
      • San Nicolás, Argentina, B2900DMH
        • Research Site
      • San Vicente, Argentina, 5006
        • Research Site
    • Alberta
      • Calgary, Alberta, Canada, T2H 2G4
        • Research Site
      • Red Deer, Alberta, Canada, T4N 6V7
        • Research Site
    • Ontario
      • Brampton, Ontario, Canada, L6T 0G1
        • Research Site
      • Brampton, Ontario, Canada, L6S 0S9
        • Research Site
      • Concord, Ontario, Canada, L4K 4M2
        • Research Site
      • Etobicoke, Ontario, Canada, M9R 4E1
        • Research Site
      • Toronto, Ontario, Canada, M4G 3E8
        • Research Site
      • Concepción, Chile
        • Research Site
      • Nunoa, Chile, 8520398
        • Research Site
      • Santiago, Chile
        • Research Site
      • Santiago, Chile, 8320000
        • Research Site
      • Santiago, Chile, 7500021
        • Research Site
      • Santiago, Chile, 7500710
        • Research Site
      • Victoria, Chile
        • Research Site
      • Chuo-ku, Japan, 103-0027
        • Research Site
      • Fukuoka-shi, Japan, 815-8555
        • Research Site
      • Ise-shi, Japan, 516-8512
        • Research Site
      • Kisarazu-shi, Japan, 292-8535
        • Research Site
      • Koshigaya-shi, Japan, 343-8577
        • Research Site
      • Nagano-shi, Japan, 388-8004
        • Research Site
      • Nagoya, Japan, 451-8511
        • Research Site
      • Nishinomiya-Shi, Japan, 662-0918
        • Research Site
      • Osaka-shi, Japan, 530-0001
        • Research Site
      • Osaka-shi, Japan, 558-8558
        • Research Site
      • Sayama-Shi, Japan
        • Research Site
      • Gangnam-Gu, Korea, Republic of, 6273
        • Research Site
      • Goyang-si, Korea, Republic of, 10444
        • Research Site
      • Jongno-gu, Korea, Republic of, 110-746
        • Research Site
      • Seongbuk-Gu, Korea, Republic of, 02841
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Research Site
      • Suwon, Korea, Republic of, 16499
        • Research Site
      • Wonju-si, Korea, Republic of, 26426
        • Research Site
      • Piura, Peru
        • Research Site
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Research Site
      • Huntsville, Alabama, United States, 35805
        • Research Site
    • Arizona
      • Mesa, Arizona, United States, 85210
        • Research Site
    • California
      • Alhambra, California, United States, 91801
        • Research Site
      • Glendale, California, United States, 91204
        • Research Site
      • Granada Hills, California, United States, 91344
        • Research Site
      • Huntington Park, California, United States, 90255
        • Research Site
      • Northridge, California, United States, 91324
        • Research Site
      • Sacramento, California, United States, 95821
        • Research Site
      • San Diego, California, United States, 92123
        • Research Site
      • San Dimas, California, United States, 91773
        • Research Site
      • Vacaville, California, United States, 95687
        • Research Site
    • Florida
      • Fleming Island, Florida, United States, 32003
        • Research Site
      • Hialeah, Florida, United States, 33016
        • Research Site
      • Jacksonville, Florida, United States, 32204
        • Research Site
      • Miami, Florida, United States, 33015
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States, 30338
        • Research Site
    • Hawaii
      • Honolulu, Hawaii, United States, 96814
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Research Site
      • Chicago, Illinois, United States, 60643
        • Research Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Research Site
    • Kansas
      • Manhattan, Kansas, United States, 66502
        • Research Site
      • Topeka, Kansas, United States, 66606
        • Research Site
      • Wichita, Kansas, United States, 67214
        • Research Site
    • Michigan
      • Flint, Michigan, United States, 48504
        • Research Site
    • Nevada
      • Henderson, Nevada, United States, 89014
        • Research Site
      • Las Vegas, Nevada, United States, 89129
        • Research Site
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Research Site
      • Greensboro, North Carolina, United States, 27408
        • Research Site
      • Greenville, North Carolina, United States, 27834
        • Research Site
      • Morehead City, North Carolina, United States, 28557
        • Research Site
    • Ohio
      • Maumee, Ohio, United States, 43537
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73116
        • Research Site
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Research Site
    • Rhode Island
      • East Providence, Rhode Island, United States, 02915
        • Research Site
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Research Site
    • Tennessee
      • Memphis, Tennessee, United States, 38119
        • Research Site
    • Texas
      • Cypress, Texas, United States, 77429
        • Research Site
      • Houston, Texas, United States, 77004
        • Research Site
      • Houston, Texas, United States, 77079
        • Research Site
      • Katy, Texas, United States, 77450
        • Research Site
      • San Antonio, Texas, United States, 78229
        • Research Site
      • San Antonio, Texas, United States, 78251
        • Research Site
      • San Antonio, Texas, United States, 78212
        • Research Site
    • Utah
      • Saint George, Utah, United States, 84790
        • Research Site
    • Virginia
      • Burke, Virginia, United States, 22015
        • Research Site
    • Washington
      • Tacoma, Washington, United States, 98405
        • Research Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 101 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria

  1. Adult men or women ≥ 18 years of age.
  2. Diabetic kidney disease DKD defined as:

    1. diagnosis of T2DM
    2. eGFR 25-75 mL/min/1.73 m2
    3. UACR 100-3000 mg albumin/g creatinine
  3. BP ≤ 150/100 mmHg
  4. Stable dose of ACEi or ARB Key Exclusion Criteria

1. Serum potassium > 5.5 mmol/L 2. Significant hepatic disease 3. Hemoglobin A1c > 10.5 % 4. B-type natriuretic peptide level > 200 pg/mL 5. History of clinically significant heart disease 6. Anticipated dialysis or renal transplantation within 1 year 7. History of underlying condition that predisposes the subject to infections 8. Significant infection (viral, bacterial, or fungal) 9. Amputation due to peripheral artery disease 10. Subjects with a positive diagnostic nucleic acid test for SARS-CoV-2 11. Pregnancy, breastfeeding or intention to become pregnant during the course of the study, 12. Any other medical condition or clinically relevant abnormal findings in physical examination, laboratory results, or electrocardiogram (ECG) during screening that, in the opinion of the investigator, may compromise the safety of the subject in the study, reduce the subject's ability to participate in the study, or interfere with evaluation of the investigational product

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).
Dose 1, Dose 2, Dose 3, Dose 4
Dapagliflozin 10 mg
Experimental: Group 2
MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).
Dose 1, Dose 2, Dose 3, Dose 4
Dapagliflozin 10 mg
Experimental: Group 3
MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).
Dose 1, Dose 2, Dose 3, Dose 4
Dapagliflozin 10 mg
Experimental: Group 4
MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).
Dose 1, Dose 2, Dose 3, Dose 4
Dapagliflozin 10 mg
Placebo Comparator: Group 5
Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).
Placebo
Dapagliflozin 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urine albumin:creatinine ratio (UACR)
Time Frame: Baseline to Day 169 (24 weeks)
Change compared to placebo
Baseline to Day 169 (24 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability by assessment of adverse events
Time Frame: Visit 1 (Screening) to Day 230 (End of Study)
To assess the number Treatment Emergent Adverse events (TEAEs), Serious Adverse Events (SAEs), Treatment Emergent Adverse Events of Special Interest (AESIs)
Visit 1 (Screening) to Day 230 (End of Study)
Immunogenicity of MEDI3506
Time Frame: Day 1 to Day 230
Anti-drug antibodies (ADAs) incidence throughout the study
Day 1 to Day 230
UACR
Time Frame: At Day 169, baseline to Day 85 (12 weeks) or Day 85 to Day 169
Proportion of subjects with > 30%, > 40% and > 50% at Day 169, change in UACR from baseline to Day 85 and change from Day 85 to Day 169
At Day 169, baseline to Day 85 (12 weeks) or Day 85 to Day 169
Safety and tolerability by clinical laboratory evaluations
Time Frame: Visit 1(Screening) to End of study
  1. Number of subjects with clinically significant changes in hematology or clinical chemistry [Time Frame: Measurement at Day -3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169]
  2. Number of subjects with clinically significant changes in urinalysis [Time Frame: Measurement at Day -3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169]
  3. Number of subjects with clinically significant changes in BNP [Time Frame: Measurement at Day -3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169]
  4. Number of COVID-19 positive subjects with and without adverse events [Time Frame: Measurement at Day -3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169]
Visit 1(Screening) to End of study

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Outcome: Geometric mean of MEDI3506.
Time Frame: Time Frame: Measurement at screening, at Day time frame: measurement at day 29, 85 and 169
Percentage change from baseline in geometric mean of MEDI3506 concentration in plasma.
Time Frame: Measurement at screening, at Day time frame: measurement at day 29, 85 and 169
Secondary Outcome: Concentration in plasma
Time Frame: Measurement at screening, at Day 29, Day 85 and Day 169
Plasma concentration of MEDI3506 concentration in plasma
Measurement at screening, at Day 29, Day 85 and Day 169
Secondary Outcome: Anti-drug antibodies (ADAs)
Time Frame: Measurement at Day 1, Day 29, Day 85 and Day 169
Anti-drug antibodies (ADAs) during the treatment period and follow-up period
Measurement at Day 1, Day 29, Day 85 and Day 169
Secondary Outcome: Percentage change from baseline
Time Frame: Measurement at screening, Day 1, Day 29, Day 85
Percentage change from baseline in levels of biomarker of inflammation and fibrosis relevant to DKD progression including but not limited to: hsCRP, sST2, IL-33, MCP-1, TNFR1/2
Measurement at screening, Day 1, Day 29, Day 85
Safety and tolerability by assessment of vital signs
Time Frame: Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Vital sign: Systolic blood pressure (SBP)
Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Safety and tolerability by assessment of vital signs
Time Frame: Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Vital sign: Diastolic blood pressure (DBP)
Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Safety and tolerability by assessment of vital signs
Time Frame: Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Vital sign: Heart rate and respiratory rate
Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Safety and tolerability by assessment of vital signs
Time Frame: Measurement Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Vital sign: Oral body temperature
Measurement Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Safety and tolerability by assessment of vital signs
Time Frame: Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Number of subjects with an ECG determined to be abnormal and clinically significant
Measurement at Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Safety and tolerability by assessment of vital signs
Time Frame: Measurement at Day -3 and Day 169
Number of subjects with clinically significant changes in left ventricular ejection fraction
Measurement at Day -3 and Day 169

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 18, 2019

Primary Completion (Actual)

May 16, 2023

Study Completion (Actual)

May 16, 2023

Study Registration Dates

First Submitted

November 18, 2019

First Submitted That Met QC Criteria

November 18, 2019

First Posted (Actual)

November 20, 2019

Study Record Updates

Last Update Posted (Estimated)

June 16, 2023

Last Update Submitted That Met QC Criteria

June 15, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.All request 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

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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