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

Mallinckrodt38 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Systemic Lupus Erythematosus (SLE)

Interventions

ActharDRUG

Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day

PlaceboDRUG

Placebo contains the same inactive ingredients as Acthar, and is given by SC injection

Steroid DrugDRUG

The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (22)

Mallinckrodt Investigational Site

Jonesboro, Arkansas, United States

Outcomes

Primary Outcomes

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.

Time frame: within 4 weeks

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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Mallinckrodt Investigational Site

La Jolla, California, United States

Mallinckrodt Investigational Site

La Palma, California, United States

Mallinckrodt Investigational Site

Long Beach, California, United States

Mallinckrodt Investigational Site

Upland, California, United States

Mallinckrodt Investigational Site

Brandon, Florida, United States

Mallinckrodt Investigational Site

Clearwater, Florida, United States

Mallinckrodt Investigational Site

Miami Lakes, Florida, United States

Mallinckrodt Investigational Site

Orlando, Florida, United States

Mallinckrodt Investigational Site

Tampa, Florida, United States

...and 12 more locations

Time frame: 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.

Time frame: at Baseline

Physician's Global Assessment (PGA) of Disease Severity at Week 4

Time frame: at Week 4

Physician's Global Assessment (PGA) of Disease Severity at Week 8

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: at Baseline, Week 4 and Week 8 (within 8 weeks)

Number of Participants Who Meet the Definition of a Responder at Week 52

Time frame: at Week 52

Score on the SELENA-SLEDAI at Week 52

Time frame: at Week 52

Physician's Global Assessment (PGA) of Disease Severity at Week 52

Time frame: 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.

Time frame: at Week 52

Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52

Time frame: at Week 52

Krupp Fatigue Severity Score (FSS) at Week 52

Time frame: at Week 52

Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52

Time frame: at Week 52

Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52

Time frame: at Week 52

Number of Participants With a Relapse Within 52 Weeks

Time frame: within 52 weeks