A Phase 2b Diabetic Kidney Disease Study

Diabetic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04170543
• Other study ID #: D9183C00001
• Status: Completed
• Phase: Phase 2
• Start date: November 18, 2019
• Est. completion date: May 16, 2023

Study information

• Verified date: June 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 609
• Est. completion date: May 16, 2023
• Est. primary completion date: May 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• MEDI3506
Dose 1, Dose 2, Dose 3, Dose 4
• Placebo
Placebo
• Dapagliflozin
Dapagliflozin 10 mg

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Cordoba
Argentina	Research Site	Corrientes
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Pergamino
Argentina	Research Site	Ramos Mejía
Argentina	Research Site	Rosario
Argentina	Research Site	San Luis
Argentina	Research Site	San Nicolás
Argentina	Research Site	San Vicente
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Concord	Ontario
Canada	Research Site	Etobicoke	Ontario
Canada	Research Site	Red Deer	Alberta
Canada	Research Site	Toronto	Ontario
Chile	Research Site	Concepción
Chile	Research Site	Nunoa
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Victoria
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Ise-shi
Japan	Research Site	Kisarazu-shi
Japan	Research Site	Koshigaya-shi
Japan	Research Site	Nagano-shi
Japan	Research Site	Nagoya
Japan	Research Site	Nishinomiya-Shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sayama-Shi
Korea, Republic of	Research Site	Gangnam-Gu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Jongno-gu
Korea, Republic of	Research Site	Seongbuk-Gu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Wonju-si
Peru	Research Site	Piura
United States	Research Site	Alhambra	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Berlin	New Jersey
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Birmingham	Alabama
United States	Research Site	Burke	Virginia
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbia	South Carolina
United States	Research Site	Cypress	Texas
United States	Research Site	East Providence	Rhode Island
United States	Research Site	Fleming Island	Florida
United States	Research Site	Flint	Michigan
United States	Research Site	Glendale	California
United States	Research Site	Granada Hills	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	North Carolina
United States	Research Site	Henderson	Nevada
United States	Research Site	Hialeah	Florida
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Park	California
United States	Research Site	Huntsville	Alabama
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jacksonville	Florida
United States	Research Site	Katy	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Manhattan	Kansas
United States	Research Site	Maumee	Ohio
United States	Research Site	Memphis	Tennessee
United States	Research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	Morehead City	North Carolina
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Sacramento	California
United States	Research Site	Saint George	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Dimas	California
United States	Research Site	Tacoma	Washington
United States	Research Site	Topeka	Kansas
United States	Research Site	Vacaville	California
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Japan,  Korea, Republic of,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Secondary Outcome: Geometric mean of MEDI3506.	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
Other	Secondary Outcome: Concentration in plasma	Plasma concentration of MEDI3506 concentration in plasma	Measurement at screening, at Day 29, Day 85 and Day 169
Other	Secondary Outcome: Anti-drug antibodies (ADAs)	Anti-drug antibodies (ADAs) during the treatment period and follow-up period	Measurement at Day 1, Day 29, Day 85 and Day 169
Other	Secondary Outcome: Percentage change from baseline	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
Other	Safety and tolerability by assessment of vital signs	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
Other	Safety and tolerability by assessment of vital signs	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
Other	Safety and tolerability by assessment of vital signs	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
Other	Safety and tolerability by assessment of vital signs	Vital sign: Oral body temperature	Measurement Day - 3, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169
Other	Safety and tolerability by assessment of vital signs	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
Other	Safety and tolerability by assessment of vital signs	Number of subjects with clinically significant changes in left ventricular ejection fraction	Measurement at Day -3 and Day 169
Primary	Urine albumin:creatinine ratio (UACR)	Change compared to placebo	Baseline to Day 169 (24 weeks)
Secondary	Safety and Tolerability by assessment of adverse events	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)
Secondary	Immunogenicity of MEDI3506	Anti-drug antibodies (ADAs) incidence throughout the study	Day 1 to Day 230
Secondary	UACR	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
Secondary	Safety and tolerability by clinical laboratory evaluations	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]; 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]; 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]; 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