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

Mallinckrodt

Status and phase: Completed; Phase 4

Conditions: Systemic Lupus Erythematosus (SLE)

Treatments: Drug: Placebo; Drug: Steroid Drug; Drug: Acthar

Study type: Interventional

Funder types: Industry

Identifiers

NCT01753401

QSC01-SLE-01

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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38 participants in 4 patient groups, including a placebo group

Period 2: Placebo/Acthar

Experimental group

Description:

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.

Treatment:

Drug: Acthar

Drug: Steroid Drug

Drug: Placebo

Period 2: Acthar/Acthar

Experimental group

Description:

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.

Treatment:

Drug: Acthar

Drug: Steroid Drug

Period 1: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Steroid Drug

Drug: Placebo

Period 1: Acthar

Experimental group

Description:

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.

Treatment:

Drug: Acthar

Drug: Steroid Drug