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A Phase 2b Diabetic Kidney Disease Study

Primary Purpose

Diabetic Kidney Disease

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

MEDI3506

Placebo

Dapagliflozin

About this trial

This is an interventional treatment trial for Diabetic Kidney Disease

Eligibility Criteria

18 Years - 101 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria

Adult men or women ≥ 18 years of age.
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
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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

Group 1

Group 2

Group 3

Group 4

Group 5

Arm Description

MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).

MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).

MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).

MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).

Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).

Outcomes

Primary Outcome Measures

Urine albumin:creatinine ratio (UACR)

Change compared to placebo

Secondary Outcome Measures

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)

Immunogenicity of MEDI3506

Anti-drug antibodies (ADAs) incidence throughout the study

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

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]

Full Information

NCT ID

NCT04170543

First Posted

November 18, 2019

Last Updated

June 15, 2023

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT04170543

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

November 18, 2019 (Actual)

Primary Completion Date

May 16, 2023 (Actual)

Study Completion Date

May 16, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Kidney Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This is a double-blinded study in which MEDI3506 and placebo. Neither the subject nor any of the investigator or sponsor staff who are involved in the treatment or clinical evaluation of the subjects will be aware of the treatment received.

Allocation

Randomized

Enrollment

609 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).

Arm Title

Group 2

Arm Type

Experimental

Arm Description

MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).

Arm Title

Group 3

Arm Type

Experimental

Arm Description

MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).

Arm Title

Group 4

Arm Type

Experimental

Arm Description

MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).

Arm Title

Group 5

Arm Type

Placebo Comparator

Arm Description

Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).

Intervention Type

Drug

Intervention Name(s)

MEDI3506

Intervention Description

Dose 1, Dose 2, Dose 3, Dose 4

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin

Intervention Description

Dapagliflozin 10 mg

Primary Outcome Measure Information:

Title

Urine albumin:creatinine ratio (UACR)

Description

Change compared to placebo

Time Frame

Baseline to Day 169 (24 weeks)

Secondary Outcome Measure Information:

Title

Safety and Tolerability by assessment of adverse events

Description

To assess the number Treatment Emergent Adverse events (TEAEs), Serious Adverse Events (SAEs), Treatment Emergent Adverse Events of Special Interest (AESIs)

Time Frame

Visit 1 (Screening) to Day 230 (End of Study)

Title

Immunogenicity of MEDI3506

Description

Anti-drug antibodies (ADAs) incidence throughout the study

Time Frame

Day 1 to Day 230

Title

UACR

Description

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

Time Frame

At Day 169, baseline to Day 85 (12 weeks) or Day 85 to Day 169

Title

Safety and tolerability by clinical laboratory evaluations

Description

Time Frame

Visit 1(Screening) to End of study

Other Pre-specified Outcome Measures:

Title

Secondary Outcome: Geometric mean of MEDI3506.

Description

Percentage change from baseline in geometric mean of MEDI3506 concentration in plasma.

Time Frame

Time Frame: Measurement at screening, at Day time frame: measurement at day 29, 85 and 169

Title

Secondary Outcome: Concentration in plasma

Description

Plasma concentration of MEDI3506 concentration in plasma

Time Frame

Measurement at screening, at Day 29, Day 85 and Day 169

Title

Secondary Outcome: Anti-drug antibodies (ADAs)

Description

Anti-drug antibodies (ADAs) during the treatment period and follow-up period

Time Frame

Measurement at Day 1, Day 29, Day 85 and Day 169

Title

Secondary Outcome: Percentage change from baseline

Description

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

Time Frame

Measurement at screening, Day 1, Day 29, Day 85

Title