Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients

NCT01601236 | Completed Phase 2 Results

• 1 other identifier: QSC01-DN-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 10

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.

Conditions

Diabetic Nephropathy

Keywords

H.P. Acthar Gel; Acthar; diabetic nephropathy; proteinuria; nephrotic syndrome

Outcome Measures

Primary Outcomes (1)

• 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

  Visit 12 (Week 36)

Secondary Outcomes (8)

• Percent Change in eGFR at Visit 17

  Visit 17 (Week 52)

• 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)

• Complete or Partial Remission of Proteinuria

  Visit 12 (Week 36) and Visit 17 (Week 52)

• Percent Change in eGFR Calculated Using Cystatin C

  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

Other Outcomes (1)

• Change in Mean HbA1c

  Week 36

Study Arms (6)

Acthar 8 U (0.1 mL) daily

EXPERIMENTAL

Repository Corticotropin Injection

Drug: Repository Corticotropin Injection

Placebo (0.1 mL) daily

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Acthar 16 U (0.2 mL) daily

EXPERIMENTAL

Repository Corticotropin Injection

Drug: Repository Corticotropin Injection

Placebo (0.2 mL) daily

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Acthar 32 U (0.4 mL) daily

EXPERIMENTAL

Repository Corticotropin Injection

Drug: Repository Corticotropin Injection

Placebo (0.4 mL) daily

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Repository Corticotropin Injection DRUG

H.P. Acthar Gel (repository corticotropin injection) is administered via daily SC injection for 36 weeks in the three dose groups \[8 U (0.1 mL), 16 U (0.2 mL), or 32 U (0.4 mL)\].

Also known as: H.P. Acthar Gel (repository corticotropin injection), Acthar, ACTH Gel, ACTH

Acthar 16 U (0.2 mL) daily; Acthar 32 U (0.4 mL) daily; Acthar 8 U (0.1 mL) daily

Placebo DRUG

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.

Placebo (0.1 mL) daily; Placebo (0.2 mL) daily; Placebo (0.4 mL) daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (10)

Questcor Investigational Site

Roseville, California, 95661, United States

Location

Questcor Investigational Site

Cooper City, Florida, 33024, United States

Location

Questcor Investigational Site

Miami Springs, Florida, 33166, United States

Location

Questcor Investigational Site

The Bronx, New York, 10461, United States

Location

Questcor Investigational Site

Columbus, Ohio, 43210, United States

Location

Questcor Investigational Site

Bethlehem, Pennsylvania, 18017, United States

Location

Questcor Investigational Site

Chattanooga, Tennessee, 37408, United States

Location

Questcor Investigational Site

Greenville, Texas, 75402, United States

Location

Questcor Investigational Site

Houston, Texas, 77030, United States

Location

Questcor Investigational Site

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetic Nephropathies; Proteinuria; Nephrotic Syndrome

Interventions

Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nephrosis

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Limitations and Caveats

Groups 5 \& 6 were closed when 2 of the 1st 4 subjects met predefined tolerability criteria. Enrollment terminated early at 34/40 subjects due to slow recruitment.16 of 34 subjects discontinued prior to collecting primary endpoint data at week 36.

Results Point of Contact

• Title: Medical Information Call Center
• Organization: Mallinckrodt

clinicaltrials@mnk.com

800-556-3314

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 15, 2012
• First Posted: May 17, 2012
• Study Start: May 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: November 18, 2019
• Results First Posted: July 24, 2017

Record last verified: 2017-07

Locations

US (10)