A Phase 2b Diabetic Kidney Disease Study

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
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: MEDI3506; Drug: Dapagliflozin

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

Study Locations

• Argentina
  • 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
• Canada
  • 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
• Chile
  • 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
• Japan
  • 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
• Korea, Republic of
  • 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
• Peru
  • Piura, Peru
    • Research Site
• United States
  • 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

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

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Day 169 (Week 24) in UACR - Per Protocol Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. For the intercurrent events, if a subject is lost to follow-up (EOT), discontinues treatment due to AE, or uses prohibited medication, the UACR data are treated as missing on or after the event and no imputation is performed. The LS means of percent change and difference in percent change, corresponding 90% confidence intervals are calculated based on a mixed model with repeated measures (MMRM) of log (UACR post-baseline/UACR baseline) as the response, adjusting for fixed effects of treatment, visit, and treatment-by-visit interaction, SGLT2i, region (Japan or ROW), baseline log UACR, and baseline log UACR-by-visit interaction. The MMRM includes UACR values at protocol specified visits from baseline up to Day 169.	From baseline to Day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Day 85 (Week 12) in UACR - Per Protocol Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. For the intercurrent events, if a subject is lost to follow-up (EOT), discontinues treatment due to AE, or uses prohibited medication, the UACR data are treated as missing on or after the event and no imputation is performed. The LS means of percent change and difference in percent change, corresponding 90% confidence intervals are calculated based on a mixed model with repeated measures (MMRM) of log (UACR post-baseline/UACR baseline) as the response, adjusting for fixed effects of treatment, visit, and treatment-by-visit interaction, SGLT2i, region (Japan or ROW), baseline log UACR, and baseline log UACR-by-visit interaction. The MMRM includes UACR values at protocol specified visits from baseline up to Day 169.	From baseline to Day 85
Percent Change From Day 85 (Week 12) to Day 169 (Week 24) in UACR - Per Protocol Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. For the intercurrent events, if a subject is lost to follow-up (EOT), discontinues treatment due to AE, or uses prohibited medication, the UACR data are treated as missing on or after the event and no imputation is performed. The LS means of percent change and difference in percent change, corresponding 90% confidence intervals are calculated based on a mixed model with repeated measures (MMRM) of log (UACR post-baseline/UACR baseline) as the response, adjusting for fixed effects of treatment, visit, and treatment-by-visit interaction, SGLT2i, region (Japan or ROW), baseline log UACR, and baseline log UACR-by-visit interaction. The MMRM includes UACR values at protocol specified visits from Day 85 up to Day 169.	From Day 85 to Day 169
Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Per Protocol Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. Only participants with values at Baseline and Day 169 are included.	Baseline and Day 169
Percent Change From Baseline to Day 169 (Week 24) in UACR - Full Analysis Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. For the intercurrent events, if a subject is lost to follow-up (EOT), discontinues treatment due to AE, or uses prohibited medication, the UACR data are treated as missing on or after the event and no imputation is performed. The LS means of percent change and difference in percent change, corresponding 90% confidence intervals are calculated based on a mixed model with repeated measures (MMRM) of log (UACR post-baseline/UACR baseline) as the response, adjusting for fixed effects of treatment, visit, and treatment-by-visit interaction, SGLT2i, region (Japan or ROW), baseline log UACR, and baseline log UACR-by-visit interaction. The MMRM includes UACR values at protocol specified visits from baseline up to Day 169.	From baseline to Day 169
Percent Change From Baseline to Day 85 (Week 12) in UACR - Full Analysis Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. For the intercurrent events, if a subject is lost to follow-up (EOT), discontinues treatment due to AE, or uses prohibited medication, the UACR data are treated as missing on or after the event and no imputation is performed. The LS means of percent change and difference in percent change, corresponding 90% confidence intervals are calculated based on a mixed model with repeated measures (MMRM) of log (UACR post-baseline/UACR baseline) as the response, adjusting for fixed effects of treatment, visit, and treatment-by-visit interaction, SGLT2i, region (Japan or ROW), baseline log UACR, and baseline log UACR-by-visit interaction. The MMRM includes UACR values at protocol specified visits from baseline up to Day 169.	From baseline to Day 85
Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Full Analysis Population	UACR values are collected as triplicates at baseline and at each CSP planned visit. For each triplicate, the UACR are averaged with geometric mean. Baseline is defined as the geometric mean of UACR measurements prior to first dose of study treatment. Only participants with values at Baseline and Day 169 are included.	Baseline and Day 169
Immunogenicity of MEDI3506 - PK Analysis Population	ADA prevalence: number of participants ADA positive (ADA+) at baseline and/or post-baseline. Treatment-induced ADA+: ADA not detected or missing at baseline and at least one post-baseline ADA+. Treatment-boosted ADA+: ADA+ at baseline and baseline titre is boosted by ≥ 4-fold increase at ≥ 1 post-baseline time point. Treatment-emergent ADA+ (TE-ADA + or ADA incidence): Treatment-induced ADA+ OR and Treatment-boosted ADA+.	Day 1 to Day 230
Asymptomatic Participants Tested Positive for COVID-19 During the Study - Safety Analysis Population	Participants were tested for COVID-19 during the course of the study. Descriptive analysis of asymptomatic participants tested positive for COVID-19 during the study.	Day 1 to Day 230
Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events Among COVID-19 Positive Participants - Safety Analysis Population	For participants tested positive for COVID-19 during the intervention and follow-up periods, this analysis provides: the number and proportion of subjects with any treatment-emergent adverse event; the number and proportion of subjects with any treatment-emergent serious adverse event	Day 1 to Day 230

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of MEDI3506 - PK Analysis Population	MEDI3506/Tozorakimab serum concentrations were measured using a validated assay method.	Day 1, Day 29, Day 85 and Day 169

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• D9183C00001_Redacted_CSP
• D9183C00001_Redacted_CSR_Synopsis
• D9183C00001_Redacted_SAP

Study record dates

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 (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 8, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: D9183C00001

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