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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
34
H.P. Acthar Gel (repository corticotropin injection) is administered via daily SC injection for 36 weeks in the three dose groups \[8 U (0.1 mL), 16 U (0.2 mL), or 32 U (0.4 mL)\].
Placebo contains the same inactive ingredients as H.P. Acthar Gel without the active pharmaceutical ingredient (API). Placebo is administered via daily SC injection for 36 weeks in equal volumes as the Acthar comparator volumes.
Questcor Investigational Site
Roseville, California, United States
Questcor Investigational Site
Cooper City, Florida, United States
Questcor Investigational Site
Miami Springs, Florida, United States
Questcor Investigational Site
The Bronx, New York, United States
Questcor Investigational Site
Columbus, Ohio, United States
Questcor Investigational Site
Bethlehem, Pennsylvania, United States
Questcor Investigational Site
Chattanooga, Tennessee, United States
Questcor Investigational Site
Greenville, Texas, United States
Questcor Investigational Site
Houston, Texas, United States
Questcor Investigational Site
San Antonio, Texas, United States
Percent Change in Estimated Glomerular Filtration Rate (eGFR) at Visit 12
Percent change in eGFR at Visit 12 (Week 36) compared to average baseline eGFR obtained during screening
Time frame: Visit 12 (Week 36)
Percent Change in eGFR at Visit 17
Percent change in eGFR at Visit 17 (Week 52) compared to baseline eGFR obtained during screening
Time frame: Visit 17 (Week 52)
Frequency of Patients With a Doubling of Serum Creatinine, Progression to End-stage Renal Disease (ESRD), or Death
Time frame: Visit 12 (Week 36) and Visit 17 (Week 52)
Complete or Partial Remission of Proteinuria
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)
Time frame: Visit 12 (Week 36) and Visit 17 (Week 52)
Percent Change in eGFR Calculated Using Cystatin C
Percent change in eGFR calculated using cystatin C compared to baseline obtained at Visit 2.
Time frame: Visit 12 (Week 36) and Visit 17 (Week 52)
Percent Change From Baseline in eGFR by Visit
Percent change from baseline in eGFR by visit
Time frame: Visit 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17
Percent Change From Baseline in Protein to Creatinine Ratio (PCR)
Percent change from baseline in PCR
Time frame: Visits 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria
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
Time frame: Visit 12 (Week 36) and Visit 17 (Week 52)
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol
Percent change from baseline of serum total cholesterol, triglycerides, LDL, HDL, Lp(a), albumin, and cortisol
Time frame: Visit 6, 9, 12, and 17
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