A Phase 2b Diabetic Kidney Disease Study

Phase 2

Completed

Conditions: Diabetic Kidney Disease

Interventions: Drug: MEDI3506
Drug: Placebo
Drug: Dapagliflozin

Registration Number: NCT04170543

Lead Sponsor: AstraZeneca

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 609

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Dapagliflozin	MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).
Group 1	MEDI3506	MEDI3506 Dose 1 plus Dapagliflozin (Day 85 to Day 168).
Group 2	MEDI3506	MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).
Group 2	Dapagliflozin	MEDI3506 Dose 2 plus Dapagliflozin (Day 85 to Day 168).
Group 3	MEDI3506	MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).
Group 3	Dapagliflozin	MEDI3506 Dose 3 plus Dapagliflozin (Day 85 to Day 168).
Group 4	MEDI3506	MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).
Group 4	Dapagliflozin	MEDI3506 Dose 4 plus Dapagliflozin (Day 85 to Day 168).
Group 5	Placebo	Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).
Group 5	Dapagliflozin	Placebo (volume matched) plus Dapagliflozin (Day 85 to Day 168).

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Day 169 (Week 24) in UACR - Per Protocol Population	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 Outcome Measures

Name	Time	Method
Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Full Analysis Population	Baseline and 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. Only participants with values at Baseline and Day 169 are included.
Percent Change From Baseline to Day 85 (Week 12) in UACR - Per Protocol Population	From baseline to Day 85	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.
Percent Change From Baseline to Day 169 (Week 24) in UACR - Full Analysis Population	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.
Percent Change From Baseline to Day 85 (Week 12) in UACR - Full Analysis Population	From baseline to Day 85	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.
Percent Change From Day 85 (Week 12) to Day 169 (Week 24) in UACR - Per Protocol Population	From Day 85 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 Day 85 up to Day 169.
Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Per Protocol Population	Baseline and 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. Only participants with values at Baseline and Day 169 are included.
Asymptomatic Participants Tested Positive for COVID-19 During the Study - Safety Analysis Population	Day 1 to Day 230	Participants were tested for COVID-19 during the course of the study. Descriptive analysis of asymptomatic participants tested positive for COVID-19 during the study.
Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events Among COVID-19 Positive Participants - Safety Analysis Population	Day 1 to Day 230	For participants tested positive for COVID-19 during the intervention and follow-up periods, this analysis provides: * the number and proportion of subjects with any treatment-emergent adverse event * the number and proportion of subjects with any treatment-emergent serious adverse event
Immunogenicity of MEDI3506 - PK Analysis Population	Day 1 to Day 230	ADA prevalence: number of participants ADA positive (ADA+) at baseline and/or post-baseline. Treatment-induced ADA+: ADA not detected or missing at baseline and at least one post-baseline ADA+. Treatment-boosted ADA+: ADA+ at baseline and baseline titre is boosted by ≥ 4-fold increase at ≥ 1 post-baseline time point. Treatment-emergent ADA+ (TE-ADA + or ADA incidence): Treatment-induced ADA+ OR and Treatment-boosted ADA+.