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

Study Overview
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Brief Summary
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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.

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

Conditions
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Systemic Lupus Erythematosus (SLE)

Intervention / Treatment
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* Drug: Acthar
* Drug: Placebo
* Drug: Steroid Drug


Participation Criteria
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Eligibility Criteria
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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: oral prednisone (or equivalent) > 30 mg/day, any steroid injection, cyclosporine, or non-biologic investigational drug within 3 months prior to screening intravenous immunoglobulin (IVIg) or plasmapheresis within 4 months prior to screening cyclophosphamide within 6 months prior to screening; and/or 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 For the purposes of this study, osteoporosis is defined as evidence of vertebral or long bone fracture or vertebral T-score > 2.0 For the purposes of this study, history of peptic ulcer is defined as ≤ 6 months prior to screening For the purposes of this study, congestive heart failure is defined as New York Heart Association Functional Class III-IV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 2: Placebo/Acthar<br>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<br>* Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day<br>* Other names: Repository Corticotropin Injection;Drug: Placebo<br>* Placebo contains the same inactive ingredients as Acthar, and is given by SC injection<br>* Other names: Matching Placebo;Drug: Steroid Drug<br>* The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.<br>* Other names: Prednisone or equivalent;|
| Experimental: Period 2: Acthar/Acthar<br>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<br>* Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day<br>* Other names: Repository Corticotropin Injection;Drug: Steroid Drug<br>* The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.<br>* Other names: Prednisone or equivalent;|
| Placebo Comparator: Period 1: Placebo<br>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<br>* Placebo contains the same inactive ingredients as Acthar, and is given by SC injection<br>* Other names: Matching Placebo;Drug: Steroid Drug<br>* The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.<br>* Other names: Prednisone or equivalent;|
| Experimental: Period 1: Acthar<br>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<br>* Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day<br>* Other names: Repository Corticotropin Injection;Drug: Steroid Drug<br>* The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.<br>* Other names: Prednisone or equivalent;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Lupus