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Completed

NCT Number: NCT04170543

A Phase 2b Diabetic Kidney Disease Study

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

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Key information

Conditions

Diabetic Kidney Disease Diabetes Complications Diabetes Mellitus Diabetic Nephropathies Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Urogenital Diseases Urologic Diseases

Age range

18 year–101 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • 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

Treatment and study plan

MEDI3506

Drug

Dose 1, Dose 2, Dose 3, Dose 4

Placebo

Drug

Placebo

Dapagliflozin

Drug

Dapagliflozin 10 mg

Primary outcomes

  1. 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

  1. Percent Change From Baseline to Day 85 (Week 12) in UACR - Per Protocol Population

    Time frame: 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.

  2. Percent Change From Day 85 (Week 12) to Day 169 (Week 24) in UACR - Per Protocol Population

    Time frame: 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.

  3. Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Per Protocol Population

    Time frame: 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.

  4. Percent Change From Baseline to Day 169 (Week 24) in UACR - Full Analysis 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.

  5. Percent Change From Baseline to Day 85 (Week 12) in UACR - Full Analysis Population

    Time frame: 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.

  6. Proportion of Subjects With Reduction in UACR at Day 169 (Week 24) - Full Analysis Population

    Time frame: 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.

  7. Immunogenicity of MEDI3506 - PK Analysis Population

    Time frame: 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+.

  8. Asymptomatic Participants Tested Positive for COVID-19 During the Study - Safety Analysis Population

    Time frame: 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.

  9. Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events Among COVID-19 Positive Participants - Safety Analysis Population

    Time frame: 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

Other outcomes

  1. Plasma Concentration of MEDI3506 - PK Analysis Population

    Time frame: Day 1, Day 29, Day 85 and Day 169

    MEDI3506/Tozorakimab serum concentrations were measured using a validated assay method.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Nov 20, 2019
Registry last updated
Jul 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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