Clinical trial NCT04170543: A Phase 2b Diabetic Kidney Disease Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-11-20
Enrollment: 609
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible subjects will be randomized to receive MEDI3506 or placebo as follows:

Group 1: MEDI3506 Dose 1. Group 2: MEDI3506 Dose 2. Group 3: MEDI3506 Dose 3 Group 4: MEDI3506 Dose 4 Group 5: Placebo (volume matched) All subjects will receive Dapa from Day 85 to Day 168.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline to Day 169 (Week 24) in UACR - Per Protocol Population
timeFrame: From baseline to Day 169
Secondary outcomes:
measure: Percent Change From Baseline to Day 85 (Week 12) in UACR - Per Protocol Population
timeFrame: From baseline to Day 85
measure: Percent Change From Day 85 (Week 12) to Day 169 (Week 24) in UACR - Per Protocol Population
timeFrame: From Day 85 to Day 169
measure: Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Per Protocol Population
timeFrame: Baseline and Day 169
measure: Percent Change From Baseline to Day 169 (Week 24) in UACR - Full Analysis Population
timeFrame: From baseline to Day 169
measure: Percent Change From Baseline to Day 85 (Week 12) in UACR - Full Analysis Population
timeFrame: From baseline to Day 85
measure: Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Full Analysis Population
timeFrame: Baseline and Day 169
measure: Immunogenicity of MEDI3506 - PK Analysis Population
timeFrame: Day 1 to Day 230
measure: Asymptomatic Participants Tested Positive for COVID-19 During the Study - Safety Analysis Population
timeFrame: Day 1 to Day 230
measure: Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events Among COVID-19 Positive Participants - Safety Analysis Population
timeFrame: Day 1 to Day 230
Other outcomes:
measure: Plasma Concentration of MEDI3506 - PK Analysis Population
timeFrame: Day 1, Day 29, Day 85 and Day 169
Locations:
city: Birmingham
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facility: Research Site
state: Alabama
city: Huntsville
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facility: Research Site
state: Alabama
city: Mesa
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state: Arizona
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city: Glendale
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city: Sacramento
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city: San Diego
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city: Fleming Island
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city: Miami
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city: Charlotte
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city: Greensboro
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city: Greenville
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city: Morehead City
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city: Houston
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state: West Virginia
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country: Argentina
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city: Buenos Aires
country: Argentina
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city: Buenos Aires
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city: Caba
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city: Caba
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city: Pergamino
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city: San Vicente
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country: Canada
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state: Alberta
city: Red Deer
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city: Santiago
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city: Santiago
country: Chile
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city: Victoria
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country: Japan
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city: Fukuoka-shi
country: Japan
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city: Ise-shi
country: Japan
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country: Japan
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country: Japan
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city: Osaka-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Sayama-Shi
country: Japan
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city: Gangnam-Gu
country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Suwon
country: Korea, Republic of
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city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Piura
country: Peru
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Study officials:
References: