A Phase 2b Diabetic Kidney Disease Study

Study Overview
=================
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.

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

Conditions
-----------------
Diabetic Kidney Disease

Intervention / Treatment
-----------------
* Drug: MEDI3506
* Drug: Placebo
* Drug: Dapagliflozin


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria Adult men or women ≥ 18 years of age. Diabetic kidney disease DKD defined as: diagnosis of T2DM eGFR 25-75 mL/min/1.73 m2 UACR 100-3000 mg albumin/g creatinine BP ≤ 150/100 mmHg 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 101 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine albumin:creatinine ratio (UACR) | 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 | 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 | Anti-drug antibodies (ADAs) incidence throughout the study | Day 1 to Day 230 | 
| 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 | 
| 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 |