Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease

A Two-part Study Exploring the Efficacy, Safety, and Pharmacodynamics of Acthar in Systemic Lupus Erythematosus Patients With a History of Persistently Active Disease

This Phase 4 study is being performed to examine the effects of Acthar for the indicated use of treatment of SLE. This study will enroll patients with steroid-dependent, persistently active SLE with arthritic and/or cutaneous involvement.

The study will involve two periods: an 8-week double-blind period, to provide placebo-controlled safety, efficacy, and pharmacodynamic data, and an optional open-label period, to examine the prolonged effects of Acthar maintenance.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: Acthar; Drug: Placebo; Drug: Steroid Drug

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Mallinckrodt Investigational Site
  • California
    • La Jolla, California, United States, 92037
      • Mallinckrodt Investigational Site
    • La Palma, California, United States, 90623
      • Mallinckrodt Investigational Site
    • Long Beach, California, United States, 90806
      • Mallinckrodt Investigational Site
    • Upland, California, United States, 91786
      • Mallinckrodt Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Mallinckrodt Investigational Site
    • Clearwater, Florida, United States, 33765
      • Mallinckrodt Investigational Site
    • Miami Lakes, Florida, United States, 33014
      • Mallinckrodt Investigational Site
    • Orlando, Florida, United States, 32806
      • Mallinckrodt Investigational Site
    • Tampa, Florida, United States, 33614
      • Mallinckrodt Investigational Site
  • Indiana
    • Granger, Indiana, United States, 46530
      • Mallinckrodt Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mallinckrodt Investigational Site
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Mallinckrodt Investigational Site
    • Lansing, Michigan, United States, 48917
      • Mallinckrodt Investigational Site
  • New York
    • Brooklyn, New York, United States, 11201
      • Mallinckrodt Investigational Site
    • Great Neck, New York, United States, 11020
      • Mallinckrodt Investigational Site
    • New York, New York, United States, 10016
      • Mallinckrodt Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Mallinckrodt Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Mallinckrodt Investigational Site
    • Wyomissing, Pennsylvania, United States, 19610
      • Mallinckrodt Investigational Site
  • Texas
    • Houston, Texas, United States, 77004
      • Mallinckrodt Investigational Site
    • Houston, Texas, United States, 77034
      • Mallinckrodt Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female ≥ 18 years of age at screening who are able to provide informed consent
• Diagnosis of SLE according to the American College of Rheumatology revised criteria (fulfilled ≥ 4 criteria)
• Active SLE with arthritic and/or cutaneous involvement as demonstrated by a SELENA-SLEDAI score ≥ 2 (clinical manifestation must include rash and/or arthritis)
• Moderate to severe rash and/or arthritis as demonstrated by BILAG score A or B in the mucocutaneous and/or musculoskeletal body systems
• Documented history of autoantibodies to at least one of the following: anti-dsDNA, anti-Smith, or anti-cardiolipin
• Documented history of positive antinuclear antibody (ANA)
• Currently on a stable dose of prednisone (7.5 to 30 mg/day of prednisone or equivalent within the 4 weeks prior to screening). The prednisone regimen must remain stable through the double-blind phase and until the stable Acthar regimen is attained in the open-label phase.

Exclusion Criteria:

• Patients with a recent history (≤ 2 months prior to screening) of starting prednisone (or equivalent) use
• Patients with active nephritis defined as serum creatinine > 2.5 mg/dL or protein creatinine ratio (PCR) > 1.5 g/g, or patients that required hemodialysis within 3 months prior to screening
• Active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis), requiring therapeutic intervention within 3 months prior to screening
• Type 1 or type 2 diabetes mellitus (history of gestational diabetes mellitus is not an exclusion), or patients currently taking hypoglycemic medication

• History of using certain medications prior to screening:

  1. oral prednisone (or equivalent) > 30 mg/day, any steroid injection, cyclosporine, or non-biologic investigational drug within 3 months prior to screening
  2. intravenous immunoglobulin (IVIg) or plasmapheresis within 4 months prior to screening
  3. cyclophosphamide within 6 months prior to screening; and/or
  4. B-cell targeted therapy, abatacept, or any biologic investigational agent within 12 months prior to screening

• Contraindication per Acthar Prescribing Information: 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

  1. For the purposes of this study, osteoporosis is defined as evidence of vertebral or long bone fracture or vertebral T-score > 2.0
  2. For the purposes of this study, history of peptic ulcer is defined as ≤ 6 months prior to screening
  3. For the purposes of this study, congestive heart failure is defined as New York Heart Association Functional Class III-IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Period 2: Placebo/Acthar; Participants receive Placebo in Part 1, but after completion of Week 8 in the double-blind phase, patients who received Placebo may choose to participate in the optional open-label phase where they will receive an Acthar maintenance regimen for 44 weeks. The initial Acthar regimen will be assigned based on the study medication regimen the patient received at the completion of the double-blind phase (Visit 6, Week 8). Acthar regimen during Part 2 may be adjusted based on the Investigator's judgment with the goal of achieving a stable Acthar regimen no later than Week 28. Once the stable Acthar regimen is achieved, the Investigator should consider tapering the steroid regimen to a low daily dose or completely discontinue.	Drug: Acthar; Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day; Other Names: Repository Corticotropin Injection; H.P. Acthar Gel; Drug: Placebo; Placebo contains the same inactive ingredients as Acthar, and is given by SC injection; Other Names: Matching Placebo; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent
EXPERIMENTAL: Period 2: Acthar/Acthar; After completion of Week 8 in the double-blind phase, patients who received Acthar may choose to participate in the optional open-label phase where they will receive an Acthar maintenance regimen for 44 weeks. The initial Acthar regimen will be assigned based on the study medication regimen the patient received at the completion of the double-blind phase (Visit 6, Week 8). Acthar regimen may be adjusted based on the Investigator's judgment with the goal of achieving a stable Acthar regimen no later than Week 28. Once the stable Acthar regimen is achieved, the Investigator should consider tapering the steroid regimen to a low daily dose or completely discontinue.	Drug: Acthar; Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day; Other Names: Repository Corticotropin Injection; H.P. Acthar Gel; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent
PLACEBO_COMPARATOR: Period 1: Placebo; Participants receive matching placebo (in 0.5 mL daily or in 1 mL every other day) for 4 weeks. In Weeks 5-8, they will taper the study medication. Participants will continue on their stable steroid regimen during this phase of the study. After completion of Week 8 in the double-blind phase, they may choose to participate in the optional open-label phase. Participants will continue on their stable steroid regimen during this phase of the study.	Drug: Placebo; Placebo contains the same inactive ingredients as Acthar, and is given by SC injection; Other Names: Matching Placebo; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent
EXPERIMENTAL: Period 1: Acthar; Participants receive Acthar (40 units in 0.5 mL daily or 80 units in 1 mL every other day) for 4 weeks. In Weeks 5-8, they will taper the study medication. Participants will continue on their stable steroid regimen during this phase of the study. After completion of Week 8 in the double-blind phase, they may choose to participate in the optional open-label phase. Participants will continue on their stable steroid regimen during this phase of the study.	Drug: Acthar; Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day; Other Names: Repository Corticotropin Injection; H.P. Acthar Gel; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Meet the Definition of a Responder Within 4 Weeks	Participants are counted as responders based on two SLE indices: the Systemic Lupus Erythematosus Disease Activity Index amended by the SELENA group (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) Index.; decrease in SELENA-SLEDAI score from 4 to 0 for the arthritis descriptor (highest possible score is 4) and no worsening in other organ systems based on BILAG OR; decrease in SELENA-SLEDAI score from 2 to 0 for rash (highest possible score is 2) and no worsening in other organ systems based on BILAG The BILAG is a transitional index that captures changing severity of clinical manifestations. It has an ordinal scale scoring system by design that produces an overview of disease activity across eight systems. The individual system scores were not intended to be summated into a global score.	within 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Meet the Definition of a Responder Within 8 Weeks	Participants are counted as responders based on: decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG OR; decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG	within 8 weeks
Score on the SELENA-SLEDAI Within 8 Weeks	SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI). The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. Rows: Week 2, Week 4, Week 6, Week 8	within 8 weeks
BILAG Total Score Within 8 Weeks	The BILAG is a transitional index that captures changing severity of clinical manifestations that produces an overview of disease activity across eight systems. The 8 systems are scored on a scale from 0=not present to 4=worse, for the 4 week period before the assessment. The lowest possible score is 0, and the highest possible score is 32. A higher score means the symptoms are worse. Rows: Baseline, Week 4, Week 8	within 8 weeks
Physician's Global Assessment (PGA) of Disease Severity at Baseline	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.	at Baseline
Physician's Global Assessment (PGA) of Disease Severity at Week 4	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.	at Week 4
Physician's Global Assessment (PGA) of Disease Severity at Week 8	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.	at Week 8
Number of Tender or Swollen Joints Within 8 Weeks	The doctor counted the number of tender or swollen joints at Baseline, at Week 4, and at Week 8	at Baseline, Week 4, and Week 8 (within 8 weeks)
Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks	The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease. Rows: at Baseline, at Week 4, at Week 8	at Baseline, Week 4 and Week 8 (within 8 weeks)
Krupp Fatigue Severity Score (FSS) Within 8 Weeks	The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue. This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue). Rows: at Baseline, at Week 4, at Week 8	at Baseline, Week 4 and Week 8 (within 8 weeks)
Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement. Rows: at Baseline, at Week 4, at Week 8	at Baseline, Week 4 and Week 8 (within 8 weeks)
Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.	at Baseline, Week 4 and Week 8 (within 8 weeks)
Number of Participants Who Meet the Definition of a Responder at Week 52	Participants are counted as responders based on: decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG OR; decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG	at Week 52
Score on the SELENA-SLEDAI at Week 52	SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI). The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.	at Week 52
Physician's Global Assessment (PGA) of Disease Severity at Week 52	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.	at Week 52
Number of Tender or Swollen Joints at Week 52	The doctor counted the number of tender or swollen joints at Week 52.	at Week 52
Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52	The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease.	at Week 52
Krupp Fatigue Severity Score (FSS) at Week 52	The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue. This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue).	at Week 52
Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.	at Week 52
Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.	at Week 52
Number of Participants With a Relapse Within 52 Weeks		within 52 weeks

Collaborators and Investigators

• Sponsor: Mallinckrodt

Publications and helpful links

General Publications

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2013
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 19, 2012
• First Posted (ESTIMATE): December 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 14, 2020
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Lupus; SLE
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Adrenocorticotropic Hormone
• Other Study ID Numbers: QSC01-SLE-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO