Clinical trial NCT01753401: Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
Official title: A Two-part Study Exploring the Efficacy, Safety, and Pharmacodynamics of Acthar in Systemic Lupus Erythematosus Patients With a History of Persistently Active Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: SLE
Lupus
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2012-12-20
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Meet the Definition of a Responder Within 4 Weeks
timeFrame: within 4 weeks
Secondary outcomes:
measure: Number of Participants Who Meet the Definition of a Responder Within 8 Weeks
timeFrame: within 8 weeks
measure: Score on the SELENA-SLEDAI Within 8 Weeks
timeFrame: within 8 weeks
measure: BILAG Total Score Within 8 Weeks
timeFrame: within 8 weeks
measure: Physician's Global Assessment (PGA) of Disease Severity at Baseline
timeFrame: at Baseline
measure: Physician's Global Assessment (PGA) of Disease Severity at Week 4
timeFrame: at Week 4
measure: Physician's Global Assessment (PGA) of Disease Severity at Week 8
timeFrame: at Week 8
measure: Number of Tender or Swollen Joints Within 8 Weeks
timeFrame: at Baseline, Week 4, and Week 8 (within 8 weeks)
measure: Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks
timeFrame: at Baseline, Week 4 and Week 8 (within 8 weeks)
measure: Krupp Fatigue Severity Score (FSS) Within 8 Weeks
timeFrame: at Baseline, Week 4 and Week 8 (within 8 weeks)
measure: Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks
timeFrame: at Baseline, Week 4 and Week 8 (within 8 weeks)
measure: Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks
timeFrame: at Baseline, Week 4 and Week 8 (within 8 weeks)
measure: Number of Participants Who Meet the Definition of a Responder at Week 52
timeFrame: at Week 52
measure: Score on the SELENA-SLEDAI at Week 52
timeFrame: at Week 52
measure: Physician's Global Assessment (PGA) of Disease Severity at Week 52
timeFrame: at Week 52
measure: Number of Tender or Swollen Joints at Week 52
timeFrame: at Week 52
measure: Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52
timeFrame: at Week 52
measure: Krupp Fatigue Severity Score (FSS) at Week 52
timeFrame: at Week 52
measure: Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52
timeFrame: at Week 52
measure: Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52
timeFrame: at Week 52
measure: Number of Participants With a Relapse Within 52 Weeks
timeFrame: within 52 weeks
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Mallinckrodt Investigational Site
state: Arkansas
city: La Jolla
country: United States
facility: Mallinckrodt Investigational Site
state: California
city: La Palma
country: United States
facility: Mallinckrodt Investigational Site
state: California
city: Long Beach
country: United States
facility: Mallinckrodt Investigational Site
state: California
city: Upland
country: United States
facility: Mallinckrodt Investigational Site
state: California
city: Brandon
country: United States
facility: Mallinckrodt Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Mallinckrodt Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Mallinckrodt Investigational Site
state: Florida
city: Orlando
country: United States
facility: Mallinckrodt Investigational Site
state: Florida
city: Tampa
country: United States
facility: Mallinckrodt Investigational Site
state: Florida
city: Granger
country: United States
facility: Mallinckrodt Investigational Site
state: Indiana
city: Baton Rouge
country: United States
facility: Mallinckrodt Investigational Site
state: Louisiana
city: Lansing
country: United States
facility: Mallinckrodt Investigational Site
state: Michigan
city: Lansing
country: United States
facility: Mallinckrodt Investigational Site
state: Michigan
city: Brooklyn
country: United States
facility: Mallinckrodt Investigational Site
state: New York
city: Great Neck
country: United States
facility: Mallinckrodt Investigational Site
state: New York
city: New York
country: United States
facility: Mallinckrodt Investigational Site
state: New York
city: Charlotte
country: United States
facility: Mallinckrodt Investigational Site
state: North Carolina
city: Hershey
country: United States
facility: Mallinckrodt Investigational Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Mallinckrodt Investigational Site
state: Pennsylvania
city: Houston
country: United States
facility: Mallinckrodt Investigational Site
state: Texas
city: Houston
country: United States
facility: Mallinckrodt Investigational Site
state: Texas
Study officials:
affiliation: Mallinckrodt
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: 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.