Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients

Phase 2

Completed

Conditions: Diabetic Nephropathy

Interventions: Drug: Repository Corticotropin Injection
Drug: Placebo

Registration Number: NCT01601236

Lead Sponsor: Mallinckrodt

Brief Summary: This Phase 2A study is an adaptive design pilot study investigating the efficacy and safety of daily Acthar administration in diabetic patients with nephropathy and proteinuria. Patients with type 1 diabetes mellitus (T1DM) or T2DM who currently take insulin will be enrolled and randomized into 6 study groups and will be treated with either Acthar or Placebo for 36 weeks, followed by a 4 week dose taper, and a 12 week observation period. The study will compare three dose regimens of Acthar (8 U \[0.1 mL\], 16 U \[0.2 mL\], and 32 U \[0.4 mL\]) to equivalent volumes of Placebo to ensure the double-blind nature of the study.

Insulin-requiring patients are being enrolled to aid compliance with the daily SC administration of study medication and to allow for ease of blood glucose control by adjustment of current insulin therapy in the event of glycemic excursions. Routine safety measures, including glycemic control, will be monitored throughout the study. The adaptive design component of the study allows for the re-assignment of the high dose group to the mid dose group if unacceptable toxicity is noted as per study protocol in the high dose group. Efficacy will be assessed by monitoring serum creatinine, calculated eGFR, and proteinuria (via urinary protein to creatinine ratio \[PCR\]). Serum cortisol concentration and additional biomarkers in blood and urine will also be monitored.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acthar 8 U (0.1 mL) daily	Repository Corticotropin Injection	Repository Corticotropin Injection
Placebo (0.1 mL) daily	Placebo	Placebo
Acthar 16 U (0.2 mL) daily	Repository Corticotropin Injection	Repository Corticotropin Injection
Placebo (0.4 mL) daily	Placebo	Placebo
Placebo (0.2 mL) daily	Placebo	Placebo
Acthar 32 U (0.4 mL) daily	Repository Corticotropin Injection	Repository Corticotropin Injection

Primary Outcome Measures

Name	Time	Method
Percent Change in Estimated Glomerular Filtration Rate (eGFR) at Visit 12	Visit 12 (Week 36)	Percent change in eGFR at Visit 12 (Week 36) compared to average baseline eGFR obtained during screening

Secondary Outcome Measures

Name	Time	Method
Percent Change in eGFR at Visit 17	Visit 17 (Week 52)	Percent change in eGFR at Visit 17 (Week 52) compared to baseline eGFR obtained during screening
Frequency of Patients With a Doubling of Serum Creatinine, Progression to End-stage Renal Disease (ESRD), or Death	Visit 12 (Week 36) and Visit 17 (Week 52)
Percent Change From Baseline in eGFR by Visit	Visit 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17	Percent change from baseline in eGFR by visit
Percent Change From Baseline in Protein to Creatinine Ratio (PCR)	Visits 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17	Percent change from baseline in PCR
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria	Visit 12 (Week 36) and Visit 17 (Week 52)	Proportion of subjects whose best response was complete remission (PCR 0.5 g/g) or partial remission (reduction in PCR of \>50% from baseline, plus PCR≤2.5 g/g but \>0.5 g/g) of proteinuria
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol	Visit 6, 9, 12, and 17	Percent change from baseline of serum total cholesterol, triglycerides, LDL, HDL, Lp(a), albumin, and cortisol
Complete or Partial Remission of Proteinuria	Visit 12 (Week 36) and Visit 17 (Week 52)	Proportion of patients with complete remission (PCR 0.5 g/g) or partial remission (reduction in PCR of \>50% from baseline, plus PCR≤2.5 g/g but \>0.5 g/g) of proteinuria at Visit 12 (Week 36) and/or at Visit 17 (Week 52)
Percent Change in eGFR Calculated Using Cystatin C	Visit 12 (Week 36) and Visit 17 (Week 52)	Percent change in eGFR calculated using cystatin C compared to baseline obtained at Visit 2.