A Phase 2b Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of MEDI3506 in Subjects With Diabetic Kidney Disease
Overview
- Phase
- Phase 2
- Intervention
- MEDI3506
- Conditions
- Diabetic Kidney Disease
- Sponsor
- AstraZeneca
- Enrollment
- 609
- Locations
- 1
- Primary Endpoint
- Percent Change From Baseline to Day 169 (Week 24) in UACR - Per Protocol Population
- Status
- Completed
- Last Updated
- last year
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group 1
MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).
Intervention: MEDI3506
Group 1
MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).
Intervention: Dapagliflozin
Group 2
MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).
Intervention: MEDI3506
Group 2
MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).
Intervention: Dapagliflozin
Group 3
MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).
Intervention: MEDI3506
Group 3
MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).
Intervention: Dapagliflozin
Group 4
MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).
Intervention: MEDI3506
Group 4
MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).
Intervention: Dapagliflozin
Group 5
Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).
Intervention: Placebo
Group 5
Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).
Intervention: Dapagliflozin
Outcomes
Primary Outcomes
Percent Change From Baseline to Day 169 (Week 24) in UACR - Per Protocol Population
Time Frame: From baseline to Day 169
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.
Secondary Outcomes
- Percent Change From Baseline to Day 85 (Week 12) in UACR - Per Protocol Population(From baseline to Day 85)
- Percent Change From Baseline to Day 169 (Week 24) in UACR - Full Analysis Population(From baseline to Day 169)
- Percent Change From Baseline to Day 85 (Week 12) in UACR - Full Analysis Population(From baseline to Day 85)
- Percent Change From Day 85 (Week 12) to Day 169 (Week 24) in UACR - Per Protocol Population(From Day 85 to Day 169)
- Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Per Protocol Population(Baseline and Day 169)
- Asymptomatic Participants Tested Positive for COVID-19 During the Study - Safety Analysis Population(Day 1 to Day 230)
- Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events Among COVID-19 Positive Participants - Safety Analysis Population(Day 1 to Day 230)
- Immunogenicity of MEDI3506 - PK Analysis Population(Day 1 to Day 230)
- Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Full Analysis Population(Baseline and Day 169)