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Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients

Primary Purpose

Diabetic Nephropathy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Repository Corticotropin Injection
Placebo
Sponsored by
Mallinckrodt
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Nephropathy focused on measuring H.P. Acthar Gel, Acthar, diabetic nephropathy, proteinuria, nephrotic syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria (numbers 2, 3, 4, 5, 6, and 7 per protocol):

  • Body mass index ≤ 45 kg/m2 at screening.
  • Diagnosis of T1DM or T2DM, with HbA1c ≤ 9.0% at Visit 1A. Diagnosis of T2DM should have been made at > 30 years of age (if diabetes developed at a younger age, C-peptide level may be obtained to confirmed the diagnosis).
  • Currently insulin-requiring

    • Patients on oral hypoglycemic therapy plus insulin are eligible provided that oral hypoglycemic agent(s) administered and the dosing regimen(s) of oral hypoglycemic therapy have been stable for ≥ 12 weeks prior to screening. No changes in oral hypoglycemic therapy should be planned or anticipated during the treatment period.
  • Renal Target Disease Requirements:

    • The average of two eGFR values collected during screening (Visits 1 and 1A) must be between 20-60 mL/min/1.73m2 (calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation AND
    • Protein to creatinine ratio (PCR) ≥ 3.0 g/g OR total urine protein ≥ 3.0 g from the 24-hour urine collection returned at Visit 1A.
  • Antihypertensive Therapy:

    • Treatment with an ACEI and/or an ARB for at least 6 weeks prior to screening Visit 1A, with stable maintenance dose for ≥ 14 days prior to screening Visit 1A. No change in ACEI or ARB therapy should be planned or anticipated for the period of the study.
    • If treated with additional antihypertensive therapy(ies), duration of therapy ≥ 30 days prior to screening Visit 1A, with stable maintenance dose for ≥ 14 days prior to screening Visit 1A.
    • If the patient has documented intolerance to ACEI and/or ARB therapy (e.g. angioedema, hyperkalemia), they may be eligible for study entry, but the Medical Monitor must be consulted in these cases prior to randomization.
  • Mean systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg on ≥ 3 seated readings taken at least 5 minutes apart during the screening period at Visit 1A.

Exclusion Criteria (numbers 2, 3, 4, 5, 7, and 11 per protocol):

  • Therapies and/or Medications:

    • History of prior sensitivity to Acthar or other porcine protein products.
    • Chronic systemic corticosteroid use, defined as ≥ 20 mg of prednisone or equivalent systemic corticosteroid taken for more than 4 consecutive weeks within 6 months prior to randomization. Topical, inhaled, or intra-articular corticosteroids are allowed.
    • Planned treatment with live or live attenuated vaccines once enrolled in the study.
    • Previous treatment on a drug being investigated for the treatment of diabetic nephropathy within 6 months prior to randomization.
  • Contraindication to Acthar per Prescribing Information Section 4: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction.

    • For the purpose of this study, history of peptic ulcer is defined as ≤ 6 months prior to Visit 1A.
  • Diabetes Target Disease Exceptions:

    • Severely uncontrolled diabetes mellitus as judged by the Principal Investigator
    • HbA1c > 9% at screening Visit 1A.
    • Fasting serum glucose > 230 mg/dL at BOTH screening Visits 1 and 1A.
    • History of diabetic ketoacidosis or non-ketotic hyperosmolar coma within 6 months of screening.
    • History of ocular laser photocoagulation therapy within 6 months of screening OR diabetic retinopathy, diabetic macular edema, or cataracts associated with impairment of visual acuity that will affect adherence with the dosing or administration of SC injections.
    • Patients unwilling to titrate insulin for blood glucose control if adjustment of hypoglycemic therapy is required during the study.
  • Renal Target Disease Exceptions:

    • History of clinical or renal biopsy evidence of non-diabetic renal disease
    • Patients requiring diagnostic or interventional procedure requiring an intravenous contrast agent must delay screening/randomization for at least 14 days
  • Tuberculosis: Any patient with a positive Interferon-gamma release assay, OR signs and symptoms concerning for active tuberculosis.
  • Cardiovascular:

    • History of congestive heart failure (NYHA Functional Class III-IV).
    • History of dilated cardiomyopathy with ejection fraction < 40%.

      1. Exceptions require approval by the Medical Monitor.

    • Patient has had any of the following within 3 months of screening:

      1. Unstable angina
      2. Myocardial infarction
      3. Coronary artery bypass graft or percutaneous transluminal coronary angioplasty
      4. Transient ischemic attack or cerebrovascular accident
      5. Unstable arrhythmia

Sites / Locations

  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site
  • Questcor Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Acthar 8 U (0.1 mL) daily

Placebo (0.1 mL) daily

Acthar 16 U (0.2 mL) daily

Placebo (0.2 mL) daily

Acthar 32 U (0.4 mL) daily

Placebo (0.4 mL) daily

Arm Description

Repository Corticotropin Injection

Placebo

Repository Corticotropin Injection

Placebo

Repository Corticotropin Injection

Placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Percent Change in eGFR at Visit 17
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
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)
Percent Change in eGFR Calculated Using Cystatin C
Percent change in eGFR calculated using cystatin C compared to baseline obtained at Visit 2.
Percent Change From Baseline in eGFR by Visit
Percent change from baseline in eGFR by visit
Percent Change From Baseline in Protein to Creatinine Ratio (PCR)
Percent change from baseline in PCR
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
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

Full Information

First Posted
May 15, 2012
Last Updated
October 31, 2019
Sponsor
Mallinckrodt
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1. Study Identification

Unique Protocol Identification Number
NCT01601236
Brief Title
Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Adaptive Design Pilot Safety and Efficacy Study of H.P. Acthar Gel (Acthar) in Patients With Diabetic Nephropathy and Proteinuria.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mallinckrodt

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy
Keywords
H.P. Acthar Gel, Acthar, diabetic nephropathy, proteinuria, nephrotic syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The 32U group was discontinued after 2 patients met pre-specified criteria related to tolerability and patients assigned to the 32U were re-assigned to the 16U group.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acthar 8 U (0.1 mL) daily
Arm Type
Experimental
Arm Description
Repository Corticotropin Injection
Arm Title
Placebo (0.1 mL) daily
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
Acthar 16 U (0.2 mL) daily
Arm Type
Experimental
Arm Description
Repository Corticotropin Injection
Arm Title
Placebo (0.2 mL) daily
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
Acthar 32 U (0.4 mL) daily
Arm Type
Experimental
Arm Description
Repository Corticotropin Injection
Arm Title
Placebo (0.4 mL) daily
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Repository Corticotropin Injection
Other Intervention Name(s)
H.P. Acthar Gel (repository corticotropin injection), Acthar, ACTH Gel, ACTH
Intervention Description
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)].
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Change in Estimated Glomerular Filtration Rate (eGFR) at Visit 12
Description
Percent change in eGFR at Visit 12 (Week 36) compared to average baseline eGFR obtained during screening
Time Frame
Visit 12 (Week 36)
Secondary Outcome Measure Information:
Title
Percent Change in eGFR at Visit 17
Description
Percent change in eGFR at Visit 17 (Week 52) compared to baseline eGFR obtained during screening
Time Frame
Visit 17 (Week 52)
Title
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)
Title
Complete or Partial Remission of Proteinuria
Description
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)
Title
Percent Change in eGFR Calculated Using Cystatin C
Description
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)
Title
Percent Change From Baseline in eGFR by Visit
Description
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
Title
Percent Change From Baseline in Protein to Creatinine Ratio (PCR)
Description
Percent change from baseline in PCR
Time Frame
Visits 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17
Title
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria
Description
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)
Title
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol
Description
Percent change from baseline of serum total cholesterol, triglycerides, LDL, HDL, Lp(a), albumin, and cortisol
Time Frame
Visit 6, 9, 12, and 17
Other Pre-specified Outcome Measures:
Title
Change in Mean HbA1c
Description
Change from baseline mean HbA1c (%) to Week 36
Time Frame
Week 36

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (numbers 2, 3, 4, 5, 6, and 7 per protocol): Body mass index ≤ 45 kg/m2 at screening. Diagnosis of T1DM or T2DM, with HbA1c ≤ 9.0% at Visit 1A. Diagnosis of T2DM should have been made at > 30 years of age (if diabetes developed at a younger age, C-peptide level may be obtained to confirmed the diagnosis). Currently insulin-requiring Patients on oral hypoglycemic therapy plus insulin are eligible provided that oral hypoglycemic agent(s) administered and the dosing regimen(s) of oral hypoglycemic therapy have been stable for ≥ 12 weeks prior to screening. No changes in oral hypoglycemic therapy should be planned or anticipated during the treatment period. Renal Target Disease Requirements: The average of two eGFR values collected during screening (Visits 1 and 1A) must be between 20-60 mL/min/1.73m2 (calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation AND Protein to creatinine ratio (PCR) ≥ 3.0 g/g OR total urine protein ≥ 3.0 g from the 24-hour urine collection returned at Visit 1A. Antihypertensive Therapy: Treatment with an ACEI and/or an ARB for at least 6 weeks prior to screening Visit 1A, with stable maintenance dose for ≥ 14 days prior to screening Visit 1A. No change in ACEI or ARB therapy should be planned or anticipated for the period of the study. If treated with additional antihypertensive therapy(ies), duration of therapy ≥ 30 days prior to screening Visit 1A, with stable maintenance dose for ≥ 14 days prior to screening Visit 1A. If the patient has documented intolerance to ACEI and/or ARB therapy (e.g. angioedema, hyperkalemia), they may be eligible for study entry, but the Medical Monitor must be consulted in these cases prior to randomization. Mean systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg on ≥ 3 seated readings taken at least 5 minutes apart during the screening period at Visit 1A. Exclusion Criteria (numbers 2, 3, 4, 5, 7, and 11 per protocol): Therapies and/or Medications: History of prior sensitivity to Acthar or other porcine protein products. Chronic systemic corticosteroid use, defined as ≥ 20 mg of prednisone or equivalent systemic corticosteroid taken for more than 4 consecutive weeks within 6 months prior to randomization. Topical, inhaled, or intra-articular corticosteroids are allowed. Planned treatment with live or live attenuated vaccines once enrolled in the study. Previous treatment on a drug being investigated for the treatment of diabetic nephropathy within 6 months prior to randomization. Contraindication to Acthar per Prescribing Information Section 4: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction. For the purpose of this study, history of peptic ulcer is defined as ≤ 6 months prior to Visit 1A. Diabetes Target Disease Exceptions: Severely uncontrolled diabetes mellitus as judged by the Principal Investigator HbA1c > 9% at screening Visit 1A. Fasting serum glucose > 230 mg/dL at BOTH screening Visits 1 and 1A. History of diabetic ketoacidosis or non-ketotic hyperosmolar coma within 6 months of screening. History of ocular laser photocoagulation therapy within 6 months of screening OR diabetic retinopathy, diabetic macular edema, or cataracts associated with impairment of visual acuity that will affect adherence with the dosing or administration of SC injections. Patients unwilling to titrate insulin for blood glucose control if adjustment of hypoglycemic therapy is required during the study. Renal Target Disease Exceptions: History of clinical or renal biopsy evidence of non-diabetic renal disease Patients requiring diagnostic or interventional procedure requiring an intravenous contrast agent must delay screening/randomization for at least 14 days Tuberculosis: Any patient with a positive Interferon-gamma release assay, OR signs and symptoms concerning for active tuberculosis. Cardiovascular: History of congestive heart failure (NYHA Functional Class III-IV). History of dilated cardiomyopathy with ejection fraction < 40%. 1. Exceptions require approval by the Medical Monitor. Patient has had any of the following within 3 months of screening: Unstable angina Myocardial infarction Coronary artery bypass graft or percutaneous transluminal coronary angioplasty Transient ischemic attack or cerebrovascular accident Unstable arrhythmia
Facility Information:
Facility Name
Questcor Investigational Site
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Questcor Investigational Site
City
Cooper City
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
Questcor Investigational Site
City
Miami Springs
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Questcor Investigational Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Questcor Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Questcor Investigational Site
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Facility Name
Questcor Investigational Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37408
Country
United States
Facility Name
Questcor Investigational Site
City
Greenville
State/Province
Texas
ZIP/Postal Code
75402
Country
United States
Facility Name
Questcor Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Questcor Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

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Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients

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